Sample records for early postnatal exposures

  1. Adult Neuropsychological Performance Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

    PubMed Central

    Janulewicz, Patricia A; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Vieira, Veronica; Aschengrau, Ann

    2012-01-01

    This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure. PMID:22522125

  2. Early postnatal ozone exposure alters rat nodose and jugular sensory neuron development

    PubMed Central

    Zellner, Leor C.; Brundage, Kathleen M.; Hunter, Dawn D.; Dey, Richard D.

    2011-01-01

    Sensory neurons originating in nodose and jugular ganglia that innervate airway epithelium (airway neurons) play a role in inflammation observed following exposure to inhaled environmental irritants such as ozone (O3). Airway neurons can mediate airway inflammation through the release of the neuropeptide substance P (SP). While susceptibility to airway irritants is increased in early life, the developmental dynamics of afferent airway neurons are not well characterized. The hypothesis of this study was that airway neuron number might increase with increasing age, and that an acute, early postnatal O3 exposure might increase both the number of sensory airway neurons as well as the number SP-containing airway neurons. Studies using Fischer 344 rat pups were conducted to determine if age or acute O3 exposure might alter airway neuron number. Airway neurons in nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and counted by means of a novel technique employing flow cytometry. In Study 1, neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28. Numbers of total and airway neurons increased significantly between PD6 and PD10, then generally stabilized. In Study 2, animals were exposed to O3 (2 ppm) or filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O3-exposed animals displayed significantly less total neurons on PD21 than FA controls. This study shows that age-related changes in neuron number occur, and that an acute, early postnatal O3 exposure significantly alters sensory neuron development. PMID:22140294

  3. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats.

    PubMed

    Beaudin, Stephane A; Strupp, Barbara J; Strawderman, Myla; Smith, Donald R

    2017-02-01

    Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1-21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230-237; http://dx.doi.org/10.1289/EHP258.

  4. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

    PubMed Central

    Beaudin, Stephane A.; Strupp, Barbara J.; Strawderman, Myla; Smith, Donald R.

    2016-01-01

    Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. Objectives: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Methods: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Results: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. Conclusions: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258 PMID:27384154

  5. Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

    PubMed Central

    Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

    2014-01-01

    Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

  6. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

    PubMed

    Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

    2015-01-01

    Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

    PubMed Central

    Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

    2016-01-01

    Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

  8. Early postnatal exposure to cigarette smoke impairs the antigen-specific T-cell responses in the spleen.

    PubMed

    Singh, Shashi P; Razani-Boroujerdi, Seddigheh; Pena-Philippides, Juan C; Langley, Raymond J; Mishra, Neerad C; Sopori, Mohan L

    2006-12-15

    Annually, approximately two million babies are exposed to cigarette smoke in utero and postnatally through cigarette smoking of their mothers. Exposure to mainstream cigarette smoke is known to impair both innate and adaptive immunities, and it has been hypothesized that the effects of in utero exposure to cigarette smoke on children's health might primarily stem from the adverse effects of cigarette smoke on the immune system. To simulate the environment that babies from smoking mothers encounter, we examined the effects of prenatal mainstream and postnatal sidestream cigarette smoke on spleen cell responses. Results show that postnatal exposure of newborn Balb/c mouse pups to sidestream cigarette smoke through the first 6 weeks of life strongly suppresses the antibody response of spleen cells to the T-cell-dependent antigen, sheep red blood cells. The reduction in the antibody response seen within 6 weeks of postnatal smoke exposure is much quicker than the published data on the time 25 weeks) required to establish reproducible immunosuppression in adult rats and mice. Moreover, the immunosuppression is not associated with significant changes in T-cell numbers or subset distribution. While the postnatal exposure to cigarette smoke did not affect the mitogenic response of T and B cells, the exposure inhibited the T cell receptor-mediated rise in the intracellular calcium concentration. These results suggest that the early postnatal period is highly sensitive to the immunosuppressive effects of environmental tobacco smoke, and the effects are causally associated with impaired antigen-mediated signaling in T cells.

  9. Prenatal Exposure to Respiratory Syncytial Virus Alters Postnatal Immunity and Airway Smooth Muscle Contractility during Early-Life Reinfections

    PubMed Central

    Harford, Terri J.; Agrawal, Vandana; Yen-Lieberman, Belinda; Rezaee, Fariba; Piedimonte, Giovanni

    2017-01-01

    Maternal viral infections can have pathological effects on the developing fetus which last long after birth. Recently, maternal-fetal transmission of respiratory syncytial virus (RSV) was shown to cause postnatal airway hyperreactivity (AHR) during primary early-life reinfection; however, the influence of prenatal exposure to RSV on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. Therefore, we sought to determine whether maternal RSV infection impairs specific aspects of cell-mediated offspring immunity during early-life reinfections and the mechanisms leading to AHR. Red fluorescent protein-expressing recombinant RSV (rrRSV) was inoculated into pregnant rat dams at midterm, followed by primary and secondary postnatal rrRSV inoculations of their offspring at early-life time points. Pups and weanlings were tested for specific lower airway leukocyte populations by flow cytometry; serum cytokine/chemokine concentrations by multiplex ELISA and neurotrophins concentrations by standard ELISA; and ex vivo lower airway smooth muscle (ASM) contraction by physiological tissue bath. Pups born to RSV-infected mothers displayed elevated total CD3+ T cells largely lacking CD4+ and CD8+ surface expression after both primary and secondary postnatal rrRSV infection. Cytokine/chemokine analyses revealed reduced IFN-γ, IL-2, IL-12, IL-17A, IL-18, and TNF-α, as well as elevated nerve growth factor (NGF) expression. Prenatal exposure to RSV also increased ASM reactivity and contractility during early-life rrRSV infection compared to non-exposed controls. We conclude that maternal RSV infection can predispose offspring to postnatal lower airways dysfunction by altering immunity development, NGF signaling, and ASM contraction during early-life RSV reinfections. PMID:28178290

  10. Impact of Early Postnatal Androgen Exposure on Voice Development

    PubMed Central

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  11. Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

    PubMed Central

    Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

    2017-01-01

    Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

  12. Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice.

    PubMed

    Bath, Kevin G; Pimentel, Tiare

    2017-05-01

    Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we tested the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate exposure led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7-8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain- and dose-dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate exposure had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampal BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region-specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

    PubMed Central

    2017-01-01

    Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

  14. Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior.

    PubMed

    Eppolito, Amy K; Bachus, Susan E; McDonald, Craig G; Meador-Woodruff, James H; Smith, Robert F

    2010-01-01

    Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.

  15. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice

    PubMed Central

    YANAI, Shogo; HIRANO, Tetsushi; OMOTEHARA, Takuya; TAKADA, Tadashi; YONEDA, Naoki; KUBOTA, Naoto; YAMAMOTO, Anzu; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

    2017-01-01

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life. PMID:28579575

  16. Prenatal and Postnatal Cell Phone Exposures and Headaches in Children.

    PubMed

    Sudan, Madhuri; Kheifets, Leeka; Arah, Onyebuchi; Olsen, Jorn; Zeltzer, Lonnie

    2012-12-05

    Children today are exposed to cell phones early in life, and may be at the greatest risk if exposure is harmful to health. We investigated associations between cell phone exposures and headaches in children. The Danish National Birth Cohort enrolled pregnant women between 1996 and 2002. When their children reached age seven years, mothers completed a questionnaire regarding the child's health, behaviors, and exposures. We used multivariable adjusted models to relate prenatal only, postnatal only, or both prenatal and postnatal cell phone exposure to whether the child had migraines and headache-related symptoms. Our analyses included data from 52,680 children. Children with cell phone exposure had higher odds of migraines and headache-related symptoms than children with no exposure. The odds ratio for migraines was 1.30 (95% confidence interval: 1.01-1.68) and for headache-related symptoms was 1.32 (95% confidence interval: 1.23-1.40) for children with both prenatal and postnatal exposure. In this study, cell phone exposures were associated with headaches in children, but the associations may not be causal given the potential for uncontrolled confounding and misclassification in observational studies such as this. However, given the widespread use of cell phones, if a causal effect exists it would have great public health impact.

  17. Pre- and Postnatal Parental Smoking and Acute Otitis Media in Early Childhood

    PubMed Central

    Håberg, Siri E.; Bentdal, Yngvild E.; London, Stephanie J.; Kværner, Kari J.; Nystad, Wenche; Nafstad, Per

    2010-01-01

    Aim To explore associations between acute otitis media in early childhood and prenatal and postnatal tobacco smoke exposure. Methods Subjects were 32,077 children born 2000 – 2005 in the Norwegian Mother and Child Study with questionnaire data on tobacco smoke exposure and acute otitis media up to 18 months of age. Multivariate regression models were used to obtain adjusted relative risks for acute otitis media. Results Acute otitis media was slightly more common in children exposed to parental smoking. The incidence from 0–6 months was 4.7% in unexposed children, and 6.0% in children exposed both pre-and postnatally. After adjusting for postnatal exposure and covariates, the relative risk for acute otitis media 0–6 months when exposed to maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06–1.69. Maternal smoking in pregnancy was associated with acute otitis media up to 12 months of age. Compared to non-exposed children, there was a slightly increased risk of recurrent acute otitis media for children exposed both pre- and postnatally with a relative risk of 1.24, 95% confidence interval: 1.01–1.52,. Conclusion Even in a cohort with relatively low exposure levels of parental smoking, maternal smoking in pregnancy was associated with an increased risk of acute otitis media in early childhood. PMID:19764924

  18. Postnatal cocaine exposure: effects on behavior of rats in forced swim test.

    PubMed

    Magalhães, Ana; Tavares, Maria Amélia; de Sousa, Liliana

    2002-06-01

    Exposure to cocaine in early periods of postnatal life has adverse effects on behavior, namely, it induces the display of anxiety and fear-like behaviors that are associated with stress and depression. This study examined the effects of early developmental cocaine exposure in several categories of behavior observed in forced swim test. Male and female Wistar rats were given 15 mg/kg of cocaine hydrochloride/body weight/day, subcutaneously, in two daily doses, from postnatal day (PND) 1 to PND27. Controls were saline injected in the same protocol. In PND26-PND27, rats were placed in a swimming pool during 5 min in two sessions. The categories of behavior studied in this work included horizontal and vertical rotation, vibrissae clean, head clean, fast and slow swim, struggling, floating, sliding, diving, head-diving, and wagging head. Results showed differences in the frequencies of several behavioral categories that allowed the discrimination of the behaviors that may constitute "behavioral despair" indicators, as well as which behaviors are most affected by cocaine exposure. Cocaine groups were less active and more immobile than controls. These results suggest that postnatal exposure to cocaine can produce depression-like effects and affect the ability of these animals to cope with stress situations.

  19. Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

    PubMed Central

    Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

    2013-01-01

    Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

  20. Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children.

    PubMed

    Chastang, Julie; Baïz, Nour; Cadwallader, Jean Sébastien; Cadwalladder, Jean Sébastien; Robert, Sarah; Dywer, John L; Dywer, John; Charpin, Denis André; Caillaud, Denis; de Blay, Frédéric; Raherison, Chantal; Lavaud, François; Annesi-Maesano, Isabella

    2015-01-01

    The purpose of this study was to examine the association between pre and post environmental tobacco smoke (ETS) exposure and behavioral problems in schoolchildren. In the cross-sectional 6 cities Study conducted in France, 5221 primary school children were investigated. Pre- and postnatal exposure to secondhand tobacco smoke at home was assessed using a parent questionnaire. Child's behavioral outcomes (emotional symptoms and conduct problems) were evaluated by the Strengths and Difficulties Questionnaire (SDQ) completed by the parents. ETS exposure during the postnatal period and during both pre- and postnatal periods was associated with behavioral problems in children. Abnormal emotional symptoms (internalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.72 (95% Confidence Interval (CI)= 1.36-2.17), whereas the OR was estimated to be 1.38 (95% CI= 1.12-1.69) in the case of postnatal exposure only. Abnormal conduct problems (externalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.94 (95% CI= 1.51-2.50), whereas the OR was estimated to be 1.47 (95% CI=1.17-1.84) in the case of postnatal exposure only. Effect estimates were adjusted for gender, study center, ethnic origin, child age, low parental education, current physician diagnosed asthma, siblings, preterm birth and single parenthood. Postnatal ETS exposure, alone or in association with prenatal exposure, increases the risk of behavioral problems in school-age children.

  1. Assessing Susceptibility from Early-Life Exposure to Carcinogens

    PubMed Central

    Barton, Hugh A.; Cogliano, V. James; Flowers, Lynn; Valcovic, Larry; Setzer, R. Woodrow; Woodruff, Tracey J.

    2005-01-01

    Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action. PMID:16140616

  2. In utero and postnatal exposure to arsenic alters pulmonary structure and function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lantz, R. Clark; Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721; BIO5 Institute, University of Arizona, Tucson, AZ 85721

    2009-02-15

    In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airwaymore » reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.« less

  3. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

    PubMed

    Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

    2015-03-01

    The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

  4. Pre- and Postnatal Exposure to Low Dose Glufosinate Ammonium Induces Autism-Like Phenotypes in Mice

    PubMed Central

    Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

    2014-01-01

    Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 – two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods. PMID:25477793

  5. Intestinal microbiota influence the early postnatal development of the enteric nervous system.

    PubMed

    Collins, J; Borojevic, R; Verdu, E F; Huizinga, J D; Ratcliffe, E M

    2014-01-01

    Normal gastrointestinal function depends on an intact and coordinated enteric nervous system (ENS). While the ENS is formed during fetal life, plasticity persists in the postnatal period during which the gastrointestinal tract is colonized by bacteria. We tested the hypothesis that colonization of the bowel by intestinal microbiota influences the postnatal development of the ENS. The development of the ENS was studied in whole mount preparations of duodenum, jejunum, and ileum of specific pathogen-free (SPF), germ-free (GF), and altered Schaedler flora (ASF) NIH Swiss mice at postnatal day 3 (P3). The frequency and amplitude of circular muscle contractions were measured in intestinal segments using spatiotemporal mapping of video recorded spontaneous contractile activity with and without exposure to lidocaine and N-nitro-L-arginine (NOLA). Immunolabeling with antibodies to PGP9.5 revealed significant abnormalities in the myenteric plexi of GF jejunum and ileum, but not duodenum, characterized by a decrease in nerve density, a decrease in the number of neurons per ganglion, and an increase in the proportion of myenteric nitrergic neurons. Frequency of amplitude of muscle contractions were significantly decreased in the jejunum and ileum of GF mice and were unaffected by exposure to lidocaine, while NOLA enhanced contractile frequency in the GF jejunum and ileum. These findings suggest that early exposure to intestinal bacteria is essential for the postnatal development of the ENS in the mid to distal small intestine. Future studies are needed to investigate the mechanisms by which enteric microbiota interact with the developing ENS. © 2013 John Wiley & Sons Ltd.

  6. Prenatal corticosteroid exposure alters early developmental seizures and behavior

    PubMed Central

    Velíšek, Libor

    2011-01-01

    In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

  7. Association between prenatal and postnatal tobacco smoke exposure and allergies in young children.

    PubMed

    Tanaka, Keiko; Miyake, Yoshihiro

    2011-06-01

    Many studies have shown a positive association between environmental tobacco smoke (ETS) exposure and allergic disorders, whereas epidemiological evidence of the effect of maternal smoking during pregnancy on allergic diseases is inconsistent. We investigated the independent and joint effects of in utero exposure to maternal smoking and postnatal ETS exposure at home on allergic disorders among Japanese children. Study subjects were 1951 children aged 3 years. Data on maternal smoking during pregnancy and postnatal exposure to ETS at home, allergic symptoms, and potential confounders were collected through the use of a questionnaire. Outcomes were defined according to the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence values of symptoms of wheeze, asthma, and eczema in the previous 12 months were 22.0%, 8.8%, and 17.2%, respectively. We found that postnatal ETS exposure at home in the absence of in utero exposure to maternal smoking was associated with a higher prevalence of wheeze (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.67). In contrast, in utero exposure without subsequent postnatal ETS exposure at home or exposure to postnatal ETS at home in addition to in utero exposure to maternal smoking was not associated with the prevalence of wheeze. No measurable associations were observed between fetal, postnatal, or joint exposure and the prevalence of asthma or eczema. Data from this study indicate that ETS at home may be associated with a higher prevalence of wheeze among young Japanese children.

  8. Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

    PubMed

    Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

    2010-07-01

    Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

  9. Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations.

    PubMed

    Tung, Emily W Y; Yan, Han; Lefèvre, Pavine L C; Berger, Robert G; Rawn, Dorothea F K; Gaertner, Dean W; Kawata, Alice; Rigden, Marc; Robaire, Bernard; Hales, Barbara F; Wade, Michael G

    2016-06-01

    Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine-disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti-androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Pregnant Sprague-Dawley rats were exposed to the PBDE mixture from preconception to weaning (PND 21) through the diet containing 0, 0.75, 250, and 750 mg mixture/kg diet. BFR exposure induced transient reductions in body weight at PND 35 in male and from PND 30-45 in female offspring (250 and 750 mg/kg). Liver weights (PND 21) and xenobiotic metabolizing enzyme activities (PND 21 and 46) were increased in both male and female offspring exposed to 250 and 750 mg/kg diets. Furthermore, serum T4 levels were reduced at PND 21 in both,male and female offspring (250 and 750 mg/kg). At PND 21, Serum alkaline phosphatase (ALP) was decreased in males exposed to 750 mg/kg dietat, and females exposed to 250 and 750 mg/kg diets. At PND 46 ALP was significantly elevated in males (250 and 750 mg/kg). Variations in the cervical vertebrae and phalanges were observed in pups at PND 4 (250 and 750 mg/kg). Therefore, BFR exposure during gestation through to weaning alters developmental programming in the offspring. The persistence of BFRs in the environment remains a cause for concern with regards to developmental toxicity. © 2016 Wiley Periodicals, Inc.

  10. Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level.

    PubMed

    Cadiou, Hervé; Aoudé, Imad; Tazir, Bassim; Molinas, Adrien; Fenech, Claire; Meunier, Nicolas; Grosmaitre, Xavier

    2014-04-02

    Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life.

  11. Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

    PubMed

    de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

    2018-06-04

    Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nekvasil, N.; Baggio, C.

    Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressuremore » than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.« less

  13. Prenatal versus Postnatal Tobacco Smoke Exposure and Intensive Care Use in Children Hospitalized with Bronchiolitis

    PubMed Central

    Stevenson, Michelle D.; Mansbach, Jonathan M.; Mowad, Eugene; Dunn, Michelle; Clark, Sunday; Piedra, Pedro A.; Sullivan, Ashley F.; Camargo, Carlos A.

    2016-01-01

    Objective Among children hospitalized with bronchiolitis, we examined the associations between in utero exposure to maternal cigarette smoking, postnatal tobacco smoke exposure, and risk of admission to the intensive care unit (ICU). Methods We performed a 16-center, prospective cohort study of hospitalized children age <2 years with a physician admitting diagnosis of bronchiolitis. For 3 consecutive years, from November 1, 2007 until March 31, 2010, site teams collected data from participating families, including information about prenatal maternal smoking and postnatal tobacco exposure. Analyses used χ2, Fisher's exact, and Kruskal-Wallis tests and multivariable logistic regression. Results Among 2,207 enrolled children, 216 (10%) had isolated in utero exposure to maternal smoking, 168 (8%) had isolated postnatal tobacco exposure, while 115 (5%) experienced both. Adjusting for age, sex, race, birth weight, viral etiology, apnea, initial severity of retractions, initial oxygen saturation, oral intake, and postnatal tobacco exposure, children with in utero exposure to maternal smoking had greater odds of being admitted to the ICU (adjusted odds ratio (aOR) 1.51 [95% CI 1.14-2.00]). Among children with in utero exposure to maternal smoking, those with additional postnatal tobacco exposure had a greater likelihood of ICU admission (aOR 1.95 [95% CI 1.13-3.37]) compared with children without postnatal tobacco smoke exposure (aOR 1.47 [95% CI 1.05-2.04]). Conclusions Maternal cigarette smoking during pregnancy puts children hospitalized with bronchiolitis at significantly higher risk of requiring intensive care use. Postnatal tobacco smoke exposure may exacerbate this risk. Health care providers should incorporate this information into counseling messages. PMID:26555856

  14. [Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR mouse brain].

    PubMed

    Bao, Xun-Di; Wang, Qu-Nan; Li, Fang-Fang; Chai, Xiao-Yu; Gao, Ye

    2011-04-01

    To evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period. Two male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot. GFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05). Early postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.

  15. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

    PubMed Central

    Brown, Traci A.; Holian, Andrij; Pinkerton, Kent E.; Lee, Joong Won; Cho, Yoon Hee

    2016-01-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

  16. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

    PubMed

    Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

    2016-07-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

  17. Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats

    PubMed Central

    Torres-Reveron, Annelyn; Gray, Jason D.; Melton, Jay T.; Punsoni, Michael; Tabori, Nora E.; Ward, Mary J.; Frys, Kelly; Iadecola, Costantino; Milner, Teresa A.

    2009-01-01

    To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, I.P.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7 to 35. Thirty-nine days after the last MPH administration (PND76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7–11/group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6 ± 1.2 to 126 ± 1.8 mmHg; p<0.05), assessed on PND130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6/group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood. PMID:19100815

  18. The Effects of Prenatal and Early-Postnatal Exposure to Mexico's "Oportunidades" on Long-Term Cognitive Achievement

    ERIC Educational Resources Information Center

    Sanchez, Alonso

    2016-01-01

    It is well established that children's early life environments can have significant consequences on their long-term outcomes. Yet, there is still limited empirical evidence on the effects that being exposed during the prenatal and early postnatal periods to positive shocks, such as conditional cash transfers, has on long-term cognitive function.…

  19. Early detection and treatment of postnatal depression in primary care.

    PubMed

    Davies, Bronwen R; Howells, Sarah; Jenkins, Meryl

    2003-11-01

    Postnatal depression has a relatively high incidence and gives rise to considerable morbidity. There is sound evidence supporting the use of the Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal depression. This paper reports on a project developed by two health visitors and a community mental health nurse working in the United Kingdom. The aim of the project was to improve the early detection and treatment of postnatal depression in the population of the general practice to which they were attached. The health visitors screened for postnatal depression in the course of routine visits on four occasions during the first postpartum year. Women identified as likely to be suffering from postnatal depression were offered 'listening visits' as a first-line intervention, with referral on to the general practitioner and/or community mental health nurse if indicated. Data collected over 3 years showed that the project succeeded in its aim of enhancing early detection and treatment of postnatal depression. These findings replicate those of other studies. The data also showed that a substantial number of women were identified for the first time as likely to be suffering from postnatal depression at 12 months postpartum. Women screened for the first time at 12 months were at greater risk than those who had been screened earlier than this. Health visitors should screen for postnatal depression throughout the period of their contact with mothers, not solely in the immediate postnatal period. It is particularly important to screen women who, for whatever reason, were not screened when their child was younger. The knowledge and skills needed to use the Edinburgh Postnatal Depression Scale and provide first-line intervention and onward referral can be developed at practitioner level through close collaborative working.

  20. Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.

    PubMed

    Summers, Brooke L; Rofe, Allan M; Coyle, Peter

    2009-04-01

    We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.

  1. Prenatal and postnatal cocaine exposure predict teen cocaine use

    PubMed Central

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2015-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

  2. Gestational naltrexone ameliorates fetal ethanol exposures enhancing effect on the postnatal behavioral and neural response to ethanol

    PubMed Central

    Youngentob, Steven L; Kent, Paul F; Youngentob, Lisa M

    2012-01-01

    The association between gestational exposure to ethanol and adolescent ethanol abuse is well established. Recent animal studies support the role of fetal ethanol experience-induced chemosensory plasticity as contributing to this observation. Previously, we established that fetal ethanol exposure, delivered through a dam’s diet throughout gestation, tuned the neural response of the peripheral olfactory system of early postnatal rats to the odor of ethanol. This occurred in conjunction with a loss of responsiveness to other odorants. The instinctive behavioral response to the odor of ethanol was also enhanced. Importantly, there was a significant contributory link between the altered response to the odor of ethanol and increased ethanol avidity when assessed in the same animals. Here, we tested whether the neural and behavioral olfactory plasticity, and their relationship to enhanced ethanol intake, is a result of the mere exposure to ethanol or whether it requires the animal to associate ethanol’s reinforcing properties with its odor attributes. In this later respect, the opioid system is important in the mediation (or modulation) of the reinforcing aspects of ethanol. To block endogenous opiates during prenatal life, pregnant rats received daily intraperitoneal administration of the opiate antagonist naltrexone from gestational day 6–21 jointly with ethanol delivered via diet. Relative to control progeny, we found that gestational exposure to naltrexone ameliorated the enhanced postnatal behavioral response to the odor of ethanol and postnatal drug avidity. Our findings support the proposition that in utero ethanol-induced olfactory plasticity (and its relationship to postnatal intake) requires, at least in part, the associative pairing between ethanol’s odor quality and its reinforcing aspects. We also found suggestive evidence that fetal naltrexone ameliorated the untoward effects of gestational ethanol exposure on the neural response to non-fetal-exposure

  3. Early androgen exposure and human gender development.

    PubMed

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  4. Association of prenatal exposure to maternal smoking and postnatal exposure to household smoking with dental caries in 3-year-old Japanese children.

    PubMed

    Tanaka, Keiko; Miyake, Yoshihiro; Nagata, Chisato; Furukawa, Shinya; Arakawa, Masashi

    2015-11-01

    Epidemiological studies of the association between smoking exposure and dental caries are limited. The purpose of this cross-sectional study was to examine the association between prenatal and postnatal secondhand smoke (SHS) exposure and the prevalence of dental caries in primary dentition in young Japanese children. Study subjects were 6412 children aged 3 years. Information on exposure to maternal smoking during pregnancy and postnatal SHS exposure at home was collected via parent questionnaire. Children were classified as having dental caries if one or more primary teeth had decayed or had been filled. Compared with never smoking during pregnancy, maternal smoking in the first trimester of pregnancy was significantly associated with an increased prevalence of dental caries in children (adjusted odds ratio=1.37, 95% confidence interval: 1.03-1.80). Postnatal SHS exposure was also positively associated with dental caries, with a significant positive exposure-response relationship. Compared with children not exposed to prenatal maternal smoking or postnatal SHS at home, those exposed to both prenatal and postnatal smoking had higher odds of dental caries (adjusted odds ratio=1.62, 95% confidence interval: 1.23-2.11). Our findings suggest that maternal smoking during pregnancy and postnatal SHS exposure may be associated with an increased prevalence of dental caries in primary dentition. Copyright © 2015. Published by Elsevier Inc.

  5. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

    PubMed Central

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Results Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Conclusion Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth. PMID:26372012

  6. Problematic Substance Use in Urban Adolescents: Role of Intrauterine Exposures to Cocaine and Marijuana and Post-Natal Environment

    PubMed Central

    Frank, Deborah A.; Kuranz, Seth; Appugliese, Danielle; Cabral, Howard; Chen, Clara; Crooks, Denise; Heeren, Timothy; Liebschutz, Jane; Richardson, Mark; Rose-Jacobs, Ruth

    2014-01-01

    Background Linkages between intrauterine exposures to cocaine and marijuana and adolescents’ problematic substance use have not been fully delineated. Methods Prospective longitudinal study with assessors unaware of intrauterine exposure history followed 157 urban participants from birth until late adolescence. Level of intrauterine exposures was identified by mother's report and infant’s meconium. Problematic substance use, identified by the Voice Diagnostic Interview Schedule for Children (V-DISC) or the Audio Computer Assisted Self-Interview (ACASI) and urine assay, was a composite encompassing DSM-IV indication of tolerance, abuse, and dependence on alcohol, marijuana, and tobacco and any use of cocaine, glue, or opiates. Results Twenty percent (32/157) of the sample experienced problematic substance use by age 18 years, of whom the majority (22/157) acknowledged abuse, tolerance or dependence on marijuana with or without other substances. Structural equation models examining direct and indirect pathways linking a Cox survival model for early substance initiation to a logistic regression models found effects of post-natal factors including childhood exposure to violence and household substance use, early youth substance initiation, and ongoing youth violence exposure contributing to adolescent problematic substance use. Conclusion We did not identify direct relationships between intrauterine cocaine or marijuana exposure and problematic substance use, but did find potentially modifiable post-natal risk factors also noted to be associated with problematic substance use in the general population including earlier substance initiation, exposure to violence and to household substance use. PMID:24999059

  7. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    PubMed

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Effects of Gestational and Postnatal Exposure to Chronic Intermittent Hypoxia on Diaphragm Muscle Contractile Function in the Rat

    PubMed Central

    McDonald, Fiona B.; Dempsey, Eugene M.; O'Halloran, Ken D.

    2016-01-01

    Alterations to the supply of oxygen during early life presents a profound stressor to physiological systems with aberrant remodeling that is often long-lasting. Chronic intermittent hypoxia (CIH) is a feature of apnea of prematurity, chronic lung disease, and sleep apnea. CIH affects respiratory control but there is a dearth of information concerning the effects of CIH on respiratory muscles, including the diaphragm—the major pump muscle of breathing. We investigated the effects of exposure to gestational CIH (gCIH) and postnatal CIH (pCIH) on diaphragm muscle function in male and female rats. CIH consisted of exposure in environmental chambers to 90 s of hypoxia reaching 5% O2 at nadir, once every 5 min, 8 h a day. Exposure to gCIH started within 24 h of identification of a copulation plug and continued until day 20 of gestation; animals were studied on postnatal day 22 or 42. For pCIH, pups were born in normoxia and within 24 h of delivery were exposed with dams to CIH for 3 weeks; animals were studied on postnatal day 22 or 42. Sham groups were exposed to normoxia in parallel. Following gas exposures, diaphragm muscle contractile, and endurance properties were examined ex vivo. Neither gCIH nor pCIH exposure had effects on diaphragm muscle force-generating capacity or endurance in either sex. Similarly, early life exposure to CIH did not affect muscle tolerance of severe hypoxic stress determined ex vivo. The findings contrast with our recent observation of upper airway dilator muscle weakness following exposure to pCIH. Thus, the present study suggests a relative resilience to hypoxic stress in diaphragm muscle. Co-ordinated activity of thoracic pump and upper airway dilator muscles is required for optimal control of upper airway caliber. A mismatch in the force-generating capacity of the complementary muscle groups could have adverse consequences for the control of airway patency and respiratory homeostasis. PMID:27462274

  9. Early life exposure to China's 1959-61 famine and midlife cognition.

    PubMed

    Xu, Hongwei; Zhang, Zhenmei; Li, Lydia; Liu, Jinyu

    2018-02-01

    Existing studies of the 1944-45 Dutch famine found little evidence of the association between early life malnutrition and midlife cognition. Among 2446 rural participants born between 1958 and 1963 in the China Health and Retirement Longitudinal Study, we examined effects of exposure to China's 1959-61 Great Leap Forward famine during prenatal and early postnatal life, on four cognitive measures in 2011 (baseline) and changes in cognition between 2011 and 2013 (first follow-up). We obtained difference-in-differences (DID) estimates of the famine effects by exploiting temporal variation in the timing and duration of famine exposure across six birth cohorts born between 1958 and 1963, together with geographical variation in famine severity at the prefecture level. After adjusting for gender, marital status and provincial fixed effects, we found that the 1961 cohort who experienced full-term prenatal and partial-term postnatal exposures to famine had lower scores on the Telephone Interview of Cognitive Status (TICS), a test of drawing pentagons, and general cognition at age 50 years compared with the unexposed 1963 cohort. Adjusting for education, the famine effects on drawing pentagons and general cognition were fully attenuated, but the effect on TICS persisted. We also found a robust negative famine effect on the longitudinal change in general cognition during the 2-year follow-up in the 1959 cohort. Severe nutritional deprivation during prenatal and postnatal periods has a lasting impact on cognitive performance in Chinese adults in their early 50s. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  10. Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

    PubMed

    Inomata, Kei; Taniguchi, Shinji; Yonemoto, Hiroki; Inoue, Takeshi; Kawase, Akihiko; Kondo, Yuichi

    2016-11-01

    Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO 2 ) target range (85-92%) from April 2011. Lower SpO 2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO 2 target range, during the early postnatal stage, increases the risk of DA closure failure. Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. © 2016 Japan Pediatric Society.

  11. Insights from Australian parents into educational experiences in the early postnatal period.

    PubMed

    McKellar, Lois V; Pincombe, Jan I; Henderson, Ann M

    2006-12-01

    to investigate the provision of parent education during the early postnatal period in order to gain insight that, through stakeholder collaboration, will contribute to the development of innovative strategies to enhance the provision of postnatal education in a contemporary health-care environment. the study comprises the first stage of an action-research project. The first stage of research sought to explore the experiences of mothers and fathers in the early postnatal period by conducting a questionnaire within 4 weeks of the birth of their baby. The data obtained from the questionnaire is to inform an action-research group for stage two of the project. The Children, Youth and Women's Health Service, a large city maternity hospital in South Australia, covering a range of socio-economic strata. 85 parents completed and returned the questionnaire, comprising 52 mothers and 33 fathers. an anonymous self-report questionnaire was purpose designed to provide each parent with an opportunity to reflect on their own experience, with particular emphasis given to the provision of education and support during the early postnatal period. a number of themes emerged, including a window of opportunity during the postnatal hospital stay to provide education and support, despite the reduction in the length of stay; the need for a family-centred approach to maternity services; and the significance of self and social network in the early transition to parenthood. The findings from this stage of the research, combined with a review of the literature, provide insight that will contribute to stage two of the study. At this stage, an action-research group will continue planning to develop specific actions to enhance the provision of education to parents in the early postnatal period. These actions will subsequently be implemented and assessed.

  12. Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth: A Pooled Analysis of Seven European Birth Cohorts.

    PubMed

    Iszatt, Nina; Stigum, Hein; Verner, Marc-André; White, Richard A; Govarts, Eva; Murinova, Lubica Palkovicova; Schoeters, Greet; Trnovec, Tomas; Legler, Juliette; Pelé, Fabienne; Botton, Jérémie; Chevrier, Cécile; Wittsiepe, Jürgen; Ranft, Ulrich; Vandentorren, Stéphanie; Kasper-Sonnenberg, Monika; Klümper, Claudia; Weisglas-Kuperus, Nynke; Polder, Anuschka; Eggesbø, Merete

    2015-07-01

    Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. We found a significant increase in growth associated with p,p'-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = -0.10; 95% CI: -0.19, -0.01). To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p'-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels.

  13. Postnatal exposure to methyl mercury from fish consumption: a review and new data from the Seychelles Child Development Study.

    PubMed

    Myers, Gary J; Thurston, Sally W; Pearson, Alexander T; Davidson, Philip W; Cox, Christopher; Shamlaye, Conrad F; Cernichiari, Elsa; Clarkson, Thomas W

    2009-05-01

    Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect children's developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6-, 19-, 29-, 66-, and 107-month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66- and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the children's intelligence quotient (IQ) at 107 months of age. Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. We found several associations between postnatal MeHg biomarkers and children's developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship.

  14. Methamidophos Exposure During the Early Postnatal Period of Mice: Immediate and Late-Emergent Effects on the Cholinergic and Serotonergic Systems and Behavior

    PubMed Central

    Abreu-Villaça, Yael

    2013-01-01

    Organophosphates (OPs) are among the most used pesticides. Although some OPs have had their use progressively more restricted, other OPs are being used without sufficient investigation of their effects. Here, we investigated the immediate neurochemical and delayed neurochemical and behavioral actions of the OP methamidophos to verify whether there are concerns regarding exposure during early postnatal development. From the third to the nineth postnatal day (PN), Swiss mice were sc injected with methamidophos (1mg/kg). At PN10, we assessed cholinergic and serotonergic biomarkers in the cerebral cortex and brainstem. From PN60 to PN63, mice were submitted to a battery of behavioral tests and subsequently to biochemical analyses. At PN10, the effects were restricted to females and to the cholinergic system: Methamidophos promoted increased choline transporter binding in the brainstem. At PN63, in the brainstem, there was a decrease in choline transporter, a female-only decrease in 5HT1A and a male-only increase in 5HT2 receptor binding. In the cortex, choline acetyltransferase activity was decreased and 5HT2 receptor binding was increased both in males and females. Methamidophos elicited behavioral alterations, suggestive of increased depressive-like behavior and impaired decision making. There were no significant alterations on anxiety-related measures and on memory/learning. Methamidophos elicited cholinergic and serotonergic alterations that depended on brain region, sex, and age of the animals. These outcomes, together with the behavioral effects, indicate that this OP is deleterious to the developing brain and that alterations are indeed identified long after the end of exposure. PMID:23596261

  15. Methamidophos exposure during the early postnatal period of mice: immediate and late-emergent effects on the cholinergic and serotonergic systems and behavior.

    PubMed

    Lima, Carla S; Dutra-Tavares, Ana C; Nunes, Fernanda; Nunes-Freitas, André L; Ribeiro-Carvalho, Anderson; Filgueiras, Cláudio C; Manhães, Alex C; Meyer, Armando; Abreu-Villaça, Yael

    2013-07-01

    Organophosphates (OPs) are among the most used pesticides. Although some OPs have had their use progressively more restricted, other OPs are being used without sufficient investigation of their effects. Here, we investigated the immediate neurochemical and delayed neurochemical and behavioral actions of the OP methamidophos to verify whether there are concerns regarding exposure during early postnatal development. From the third to the nineth postnatal day (PN), Swiss mice were sc injected with methamidophos (1mg/kg). At PN10, we assessed cholinergic and serotonergic biomarkers in the cerebral cortex and brainstem. From PN60 to PN63, mice were submitted to a battery of behavioral tests and subsequently to biochemical analyses. At PN10, the effects were restricted to females and to the cholinergic system: Methamidophos promoted increased choline transporter binding in the brainstem. At PN63, in the brainstem, there was a decrease in choline transporter, a female-only decrease in 5HT1A and a male-only increase in 5HT2 receptor binding. In the cortex, choline acetyltransferase activity was decreased and 5HT2 receptor binding was increased both in males and females. Methamidophos elicited behavioral alterations, suggestive of increased depressive-like behavior and impaired decision making. There were no significant alterations on anxiety-related measures and on memory/learning. Methamidophos elicited cholinergic and serotonergic alterations that depended on brain region, sex, and age of the animals. These outcomes, together with the behavioral effects, indicate that this OP is deleterious to the developing brain and that alterations are indeed identified long after the end of exposure.

  16. Prenatal and Postnatal PCB-153 and p,p'-DDE Exposures and Behavior Scores at 5–9 Years of Age among Children in Greenland and Ukraine.

    PubMed

    Rosenquist, Aske Hess; Høyer, Birgit Bjerre; Julvez, Jordi; Sunyer, Jordi; Pedersen, Henning Sloth; Lenters, Virissa; Jönsson, Bo A G; Bonde, Jens Peter; Toft, Gunnar

    2017-10-03

    Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. We investigated the association between prenatal and early-life exposures to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis( p -chlorophenyl)-ethylene ( p,p '-DDE) and behaviors in children between 5 and 9 y of age. In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother-child pairs from Greenland and Ukraine ( n =1,018), maternal serum PCB-153 and p,p '-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children's behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p '-DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre- and postnatal p,p '-DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatal p,p '-DDE, respectively. Prenatal and early postnatal exposures to p,p '-DDE and PCB-153 were associated with a higher prevalence of abnormal scores for conduct

  17. Prenatal and Postnatal PCB-153 and p,p′-DDE Exposures and Behavior Scores at 5–9 Years of Age among Children in Greenland and Ukraine

    PubMed Central

    Høyer, Birgit Bjerre; Julvez, Jordi; Sunyer, Jordi; Pedersen, Henning Sloth; Lenters, Virissa; Jönsson, Bo A.G.; Bonde, Jens Peter; Toft, Gunnar

    2017-01-01

    Background: Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. Objective: We investigated the association between prenatal and early-life exposures to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p′-DDE) and behaviors in children between 5 and 9 y of age. Methods: In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother–child pairs from Greenland and Ukraine (n=1,018), maternal serum PCB-153 and p,p′-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children’s behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. Results: The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p′-DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre- and postnatal p,p′-DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatal p,p′-DDE, respectively. Conclusion: Prenatal and early postnatal exposures to p,p′-DDE and PCB-153 were

  18. Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

    PubMed

    Fusaro, Ana Elisa; de Brito, Cyro Alves; Taniguchi, Eliana Futata; Muniz, Bruno Pacola; Victor, Jefferson Russo; Orii, Noemia Mie; Duarte, Alberto José da Silva; Sato, Maria Notomi

    2009-09-01

    Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

  19. Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype.

    PubMed

    Sexton, Timothy J; Bleckert, Adam; Turner, Maxwell H; Van Gelder, Russell N

    2015-06-21

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. In early development these cells mediate different processes, including negative phototaxis and the timing of retinal vascular development. To determine if ipRGC physiologic properties also change with development, we measured ipRGC cell density and light responses in wild-type mouse retinas at post-natal days 8, 15 and 30. Melanopsin-positive cell density decreases by 17% between post-natal days 8 and 15 and by 25% between days 8 and 30. This decrease is due specifically to a decrease in cells co-labeled with a SMI-32, a marker for alpha-on ganglion cells (corresponding to adult morphologic type M4 ipRGCs). On multi-electrode array recordings, post-natal day 8 (P8) ipRGC light responses show more robust firing, reduced adaptation and more rapid recovery from short and extended light pulses than do the light responses of P15 and P30 ipRGCs. Three ipRGC subtypes - Types I-III - have been defined in early development based on sensitivity and latency on multielectrode array recordings. We find that Type I cells largely account for the unique physiologic properties of P8 ipRGCs. Type I cells have previously been shown to have relatively short latencies and high sensitivity. We now show that Type I cells show have rapid and robust recovery from long and short bright light exposures compared with Type II and III cells, suggesting differential light adaptation mechanisms between cell types. By P15, Type I ipRGCs are no longer detectable. Loose patch recordings of P8 M4 ipRGCs demonstrate Type I physiology. Type I ipRGCs are found only in early development. In addition to their previously described high sensitivity and rapid kinetics, these cells are uniquely resistant to adaptation and recover quickly and fully to short and prolonged light exposure. Type I ipRGCs correspond to the SMI-32 positive, M4 subtype and largely lose

  20. Early postnatal nutrition determines adult physical activity and energy expenditure in female mice

    USDA-ARS?s Scientific Manuscript database

    Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1...

  1. The OBELIX project: early life exposure to endocrine disruptors and obesity.

    PubMed

    Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

    2011-12-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

  2. Effects of long-term pre- and post-natal exposure to 2.45 GHz wireless devices on developing male rat kidney.

    PubMed

    Kuybulu, Ayça Esra; Öktem, Faruk; Çiriş, İbrahim Metin; Sutcu, Recep; Örmeci, Ahmet Rıfat; Çömlekçi, Selçuk; Uz, Efkan

    2016-01-01

    The aim of the present study was to investigate oxidative stress and apoptosis in kidney tissues of male Wistar rats that pre- and postnatally exposed to wireless electromagnetic field (EMF) with an internet frequency of 2.45 GHz for a long time. The study was conducted in three groups of rats which were pre-natal, post-natal. and sham exposed groups. Oxidative stress markers and histological evaluation of kidney tissues were studied. Renal tissue malondialdehyde (MDA) and total oxidant (TOS) levels of pre-natal group were high and total antioxidant (TAS) and superoxide dismutase (SOD) levels were low. Spot urine NAG/creatinine ratio was significantly higher in pre- and post-natal groups (p < 0.001). Tubular injury was detected in most of the specimens in post-natal groups. Immunohistochemical analysis showed low-intensity staining with Bax in cortex, high-intensity staining with Bcl-2 in cortical and medullar areas of pre-natal group (p values, 0.000, 0.002, 0.000, respectively) when compared with sham group. Bcl2/Bax staining intensity ratios of medullar and cortical area was higher in pre-natal group than sham group (p = 0.018, p = 0.011). Based on this study, it is thought that chronic pre- and post-natal period exposure to wireless internet frequency of EMF may cause chronic kidney damages; staying away from EMF source in especially pregnancy and early childhood period may reduce negative effects of exposure on kidney.

  3. Preconceptional, prenatal and postnatal exposure to outdoor and indoor environmental factors on allergic diseases/symptoms in preschool children.

    PubMed

    Deng, Qihong; Lu, Chan; Ou, Cuiyun; Chen, Lv; Yuan, Hong

    2016-06-01

    Environmental factors have been found to be associated with allergic diseases, but it is unclear which environmental factor during which exposure window causes what kind of allergic diseases. We investigated association between exposure to some predominant outdoor and indoor environmental factors during preconceptional, prenatal, and postnatal periods and allergic diseases/symptoms in 2598 children in China. Children's lifetime incidence of allergic diseases and current prevalence of allergic symptoms and exposure to indoor new furniture/redecoration and mold/dampness was surveyed by a questionnaire. Exposure to outdoor air pollutants was estimated by the concentrations measured at air quality monitoring stations. Multiple logistic regression model was used to evaluate the associations between outdoor air pollutants and indoor environmental factors and allergic diseases (asthma, allergic rhinitis, and eczema) and symptoms (wheezing, night cough, and rhinitis-like). We found that preconceptional, prenatal, and postnatal exposure to outdoor industrial and traffic air pollutants were significantly associated with increase in the risk of childhood asthma, and also positively associated with allergic rhinitis and eczema. However, we cannot distinguish the effect of outdoor air pollutants and exposure windows because of their high correlations. New furniture was associated with eczema and allergic rhinitis during postnatal exposure, but redecoration associated with asthma and eczema during prenatal exposure. Indoor visible mold/damp stains was significant for eczema during prenatal exposure and asthma during postnatal exposure respectively, but window condensation was significant for all childhood allergic diseases during both prenatal and postnatal exposures. Allergic symptoms in children were found to be associated with exposure to indoor factors only. Associations between outdoor air pollutants and indoor environmental factors and childhood allergic diseases

  4. Exposure to maternal pre- and postnatal depression and anxiety symptoms: risk for major depression, anxiety disorders, and conduct disorder in adolescent offspring.

    PubMed

    Glasheen, Cristie; Richardson, Gale A; Kim, Kevin H; Larkby, Cynthia A; Swartz, Holly A; Day, Nancy L

    2013-11-01

    This study evaluated whether exposure to maternal pre- or postnatal depression or anxiety symptoms predicted psychopathology in adolescent offspring. Growth mixture modeling was used to identify trajectories of pre- and postnatal depression and anxiety symptoms in 577 women of low socioeconomic status selected from a prenatal clinic. Logistic regression models indicated that maternal pre- and postnatal depression trajectory exposure was not associated with offspring major depression, anxiety, or conduct disorder, but exposure to the high depression trajectory was associated with lower anxiety symptoms in males. Exposure to medium and high pre- and postnatal anxiety was associated with the risk of conduct disorder among offspring. Male offspring exposed to medium and high pre- and postnatal anxiety had higher odds of conduct disorder than did males with low exposure levels. Females exposed to medium or high pre- and postnatal anxiety were less likely to meet conduct disorder criteria than were females with lower exposure. To the best of our knowledge, this is the first study to examine the effect of pre- and postnatal anxiety trajectories on the risk of conduct disorder in offspring. These results suggest new directions for investigating the etiology of conduct disorder with a novel target for intervention.

  5. Exposure to Maternal Pre- and Postnatal Depression and Anxiety Symptoms: Risk for Major Depression, Anxiety Disorders, and Conduct Disorder in Adolescent Offspring

    PubMed Central

    Glasheen, Cristie; Richardson, Gale A.; Kim, Kevin H.; Larkby, Cynthia A.; Swartz, Holly A.; Day, Nancy L.

    2015-01-01

    This study evaluated whether exposure to maternal pre- or postnatal depression or anxiety symptoms predicted psychopathology in adolescent offspring. Growth mixture modeling was used to identify trajectories of pre- and postnatal depression and anxiety symptoms in 577 women of low socioeconomic status selected from a prenatal clinic. Logistic regression models indicated that maternal pre- and postnatal depression trajectory exposure was not associated with offspring major depression, anxiety, or conduct disorder but exposure to the high depression trajectory was associated with lower anxiety symptoms in males. Exposure to medium and high pre- and postnatal anxiety was associated with the risk of conduct disorder among offspring. Male offspring exposed to medium and high pre- and postnatal anxiety had higher odds of conduct disorder than males with low exposure levels. Females exposed to medium or high pre- and postnatal anxiety were less likely to meet conduct disorder criteria than females with lower exposure. To the best of our knowledge, this is the first study to examine the effect of pre- and postnatal anxiety trajectories on the risk of conduct disorder in offspring. These results suggest new directions for investigating the etiology of conduct disorder with a novel target for intervention. PMID:24229548

  6. Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism.

    PubMed

    de Carvalho, Ana Elisa Teófilo Saturi; Bassaneze, Vinícius; Forni, Maria Fernanda; Keusseyan, Aline Alfonso; Kowaltowski, Alicia Juliana; Krieger, José Eduardo

    2017-11-13

    Cardiac energy metabolism must cope with early postnatal changes in tissue oxygen tensions, hemodynamics, and cell proliferation to sustain development. Here, we tested the hypothesis that proliferating neonatal cardiomyocytes are dependent on high oxidative energy metabolism. We show that energy-related gene expression does not correlate with functional oxidative measurements in the developing heart. Gene expression analysis suggests a gradual overall upregulation of oxidative-related genes and pathways, whereas functional assessment in both cardiac tissue and cultured cardiomyocytes indicated that oxidative metabolism decreases between the first and seventh days after birth. Cardiomyocyte extracellular flux analysis indicated that the decrease in oxidative metabolism between the first and seventh days after birth was mostly related to lower rates of ATP-linked mitochondrial respiration, suggesting that overall energetic demands decrease during this period. In parallel, the proliferation rate was higher for early cardiomyocytes. Furthermore, in vitro nonlethal chemical inhibition of mitochondrial respiration reduced the proliferative capacity of early cardiomyocytes, indicating a high energy demand to sustain cardiomyocyte proliferation. Altogether, we provide evidence that early postnatal cardiomyocyte proliferative capacity correlates with high oxidative energy metabolism. The energy requirement decreases as the proliferation ceases in the following days, and both oxidative-dependent metabolism and anaerobic glycolysis subside.

  7. Does background postnatal methyl mercury exposure in toddlers affect cognition and behavior?

    PubMed

    Cao, Yang; Chen, Aimin; Jones, Robert L; Radcliffe, Jerilynn; Caldwell, Kathleen L; Dietrich, Kim N; Rogan, Walter J

    2010-01-01

    Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn 1 week before randomization and 1 week after treatment began when succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 microg/L and 0.52 microg/L and post-treatment concentrations were 0.51 microg/L and 0.48 microg/L for placebo and succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable. 2009 Elsevier Inc. All rights reserved.

  8. Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from South-Eastern Spain.

    PubMed

    González-Alzaga, Beatriz; Hernández, Antonio F; Rodríguez-Barranco, Miguel; Gómez, Inmaculada; Aguilar-Garduño, Clemente; López-Flores, Inmaculada; Parrón, Tesifón; Lacasaña, Marina

    2015-12-01

    Childrens exposure to neurotoxic compounds poses a major problem to public health because oftheir actively developing brain that makes them highly vulnerable. However, limited information is available on neuropsychological effects in children associated with pre- and postnatal exposures to pesticides. To evaluate the association between current and pre- and postnatal exposures to pesticides and their effects on neurodevelopment in children aged 6–11 years living in agricultural communities from South-Eastern Spain. An ambispective study was conducted on 305 children aged 6–11 years randomly selected from public schools of the study area. Current exposure to organophosphate pesticides was assessed measuring children's urinary levels of dialkylphosphates (DAPs). Both prenatal and postnatal residential exposure to pesticides was estimated by developing a geographical information system (GIS) technology-based index that integrated distance-weighted measure of agricultural surface, time-series of crop areas per municipality and year, and land-use maps. Neuropsychological performance was evaluated with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). The association of pre- and postnatal and current pesticide exposure with WISC-IV scale scores was assessed using multivariate linear regression models and generalized estimating equation (GEE) models, respectively. Greater urinary DAP levels were associated with a poorer performance on intelligence quotient and verbal comprehension domain, with effects being more prominent in boys than in girls. The influence of an increase in 10 ha per year in crop surface around the child's residence during the postnatal period was associated with decreased intelligence quotient, processing speed and verbal comprehension scores. As regards prenatal exposure to pesticides, a poor processing speed performance was observed. These effects were also more prominent in boys than in girls. Our results suggest that

  9. Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4 years of age.

    PubMed

    Gascon, Mireia; Vrijheid, Martine; Martínez, David; Forns, Joan; Grimalt, Joan O; Torrent, Maties; Sunyer, Jordi

    2011-04-01

    There are at present very few studies of the effects of polybromodiphenyl ethers (PBDEs), used as flame retardants in consumer products, on neurodevelopment or thyroid hormone levels in humans. The present study aims to examine the association between pre and postnatal PBDE concentrations and neurodevelopment and thyroid hormone levels in children at age 4years and isolate the effects of PBDEs from those of PCBs, DDT, DDE and HCB. A prospective birth cohort in Menorca (Spain) enrolled 482 pregnant mothers between 1997 and 1998. At 4years, children were assessed for motor and cognitive function (McCarthy Scales of Children's Abilities), attention-deficit, hyperactivity and impulsivity (ADHD-DSM-IV) and social competence (California Preschool Social Competence Scale). PBDE concentrations were measured in cord blood (N=88) and in serum of 4years olds (N=244). Among all congeners analyzed only PBDE 47 was quantified in a reasonable number of samples (LOQ=0.002ng/ml). Exposure to PBDE 47 was analyzed as a dichotomous variable: concentrations above the LOQ (exposed) and concentrations below (referents). Scores for cognitive and motor functions were always lower in children pre and postnatally exposed to PBDE47 than in referents, but none of these associations was statistically significant (β coefficient (95%CI) of the total cognition score: -2.7 (-7.0, 1.6) for postnatal exposure, and -1.4 (-9.2, 6.5) for prenatal exposure). Postnatal exposure to PBDE 47 was statistically significantly related to an increased risk of symptoms on the attention deficit subscale of ADHD symptoms (RR (95%CI)=1.8 (1.0, 3.2)) but not to hyperactivity symptoms. A statistically significant higher risk of poor social competence symptoms was observed as a consequence of postnatal PBDE 47 exposure (RR (95%CI)=2.6 (1.2, 5.9)). Adjustment for other organochlorine compounds did not influence the results. Levels of thyroid hormones were not associated to PBDE exposure. This study highlights the

  10. Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

    PubMed

    Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

    2017-01-01

    Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

  11. Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids

    PubMed Central

    Kellogg, Carol K.; Kenjarski, Thomas P.; Pleger, Gloria L.; Frye, Cheryl A.

    2013-01-01

    Fetal exposure to diazepam (DZ), a positive modulator of GABAA receptors and an agonist at mitochondrial benzodiazine receptors, induces long-term neural and behavioral effects. This study evaluated whether the early manipulation influenced the normal development of brain levels of neurosteroids or altered steroid action at GABAA receptors. Pregnant dams were injected over gestation days 14 through 20 with DZ (2.5 mg/kg) or the vehicle. Male and female offspring were analyzed at five postnatal ages. The levels of progesterone (P), dihydroprogesterone (DHP), 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), testosterone (T), dihydrotestosterone, and 5α-androstan-3α,17β diol were measured in the cerebral cortex and diencephalon. The results indicated that development of brain steroid levels and the impact of fetal DZ exposure were region- and sex-specific. Age-related changes in brain steroids did not mirror associated changes in circulating P and T. Age regulated the levels of all 3 progestins in the cerebral cortex, and fetal DZ exposure interacted with the development of P and DHP. The development of 3α,5α-THP in the cortex was markedly influenced by sex, with levels in males decreasing over postnatal development whereas they increased over postpubertal development in females. An adolescent surge in T levels was observed in male cortex and fetal DZ exposure prevented that surge. Steroid levels in the diencephalon were altered by age mainly in females, and DZ exposure had little effect in this region. The data support region-specific regulation of brain steroid synthesis. Only in the cerebral cortex are relevant mechanisms readily modifiable by fetal DZ exposure. However, neither sex nor fetal DZ exposure altered the response of GABAA receptors in adult cortex to neurosteroid. PMID:16376310

  12. Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

    PubMed

    Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

    2017-11-01

    The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

    PubMed Central

    Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

    2017-01-01

    Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development. Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes. Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001). Conclusion Preterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health. PMID:28399117

  14. Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

    PubMed

    Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

    2017-07-01

    BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

  15. Pre- and Postnatal Smoking Exposure and Risk of Atopic Eczema in Young Japanese Children: A Prospective Prebirth Cohort Study.

    PubMed

    Tanaka, Keiko; Miyake, Yoshihiro; Furukawa, Shinya; Arakawa, Masashi

    2017-07-01

    Epidemiological evidence regarding the effect of perinatal smoking exposure on atopic eczema in children continues to be inconclusive. The aim of this prospective prebirth cohort study was to investigate the association between prenatal smoking exposure and postnatal living with household smokers and the risk of atopic eczema in Japanese children aged 23 to 29 months. Study subjects were 1354 Japanese mother-child pairs. Information on the variables under study was obtained through questionnaires which were completed by mothers, first prior to delivery, then shortly after birth and subsequently around 4, 12, and 24 months after delivery. Eczema in the last 12 months was defined according to the criteria of the International Study of Asthma and Allergies in Childhood. Physician-diagnosed atopic eczema was considered present if reported by mothers. Compared with no perinatal smoking exposure, prenatal smoking exposure only was associated with an increased risk of physician-diagnosed atopic eczema (adjusted odds ratio = 7.11, 95% confidence interval: 1.43 to 27.8). Postnatal living with at least one household smoker only was not associated with the risk of physician-diagnosed atopic eczema; neither was the combination of both prenatal smoking exposure and postnatal living with at least one household smoker. No association was observed between perinatal smoking exposure status and the risk of eczema as defined according to the International Study of Asthma and Allergies in Childhood criteria. Our findings suggest that maternal smoking during pregnancy may increase the risk of atopic eczema in young children. In the present prebirth cohort study, we assessed the independent and additive effects of pre- and postnatal exposure to tobacco smoking on atopic eczema in children. Compared with no perinatal smoking exposure, prenatal smoking exposure only was significantly associated with an increased risk of atopic eczema. Postnatal smoking exposure only was not associated

  16. Prenatal exposure to diurnal temperature variation and early childhood pneumonia.

    PubMed

    Zeng, Ji; Lu, Chan; Deng, Qihong

    2017-04-01

    Childhood pneumonia is one of the leading single causes of mortality and morbidity in children worldwide, but its etiology still remains unclear. We investigate the association between childhood pneumonia and exposure to diurnal temperature variation (DTV) in different timing windows. We conducted a prospective cohort study of 2,598 children aged 3-6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed by a questionnaire administered by the parents. Individual exposure to DTV during both prenatal and postnatal periods was estimated. Logic regression models was used to examine the association between childhood pneumonia and DTV exposure in terms of odds ratios (OR) and 95% confidence interval (CI). Lifetime prevalence of childhood pneumonia in preschool children in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal DTV exposure, with adjusted OR (95%CI) =1.19 (1.02-1.38), particularly during the second trimester. However, childhood pneumonia not associated with postnatal DTV exposure. Sensitivity analysis indicated that boys are more susceptible to the pneumonia risk of diurnal temperature variation than girls. We further observed that the prevalence of childhood pneumonia was decreased in recent years as DTV shrinked. Early childhood pneumonia was associated with prenatal exposure to the diurnal temperature variation (DTV) during pregnancy, particularly in the second trimester, which suggests fetal origin of childhood pneumonia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    PubMed

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2015-01-01

    Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  18. POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE

    EPA Science Inventory

    POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE.
    J J Diliberto', J T Hamm'.2, F McQuaid', and L S Birnbaum'. 'US EPA, ORD/NHEERL/ETD, RTP, NC; 2Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC.
    2,3,7,8-Tetrachlorodibenz...

  19. Maternal postnatal psychiatric symptoms and infant temperament affect early mother-infant bonding.

    PubMed

    Nolvi, Saara; Karlsson, Linnea; Bridgett, David J; Pajulo, Marjukka; Tolvanen, Mimmi; Karlsson, Hasse

    2016-05-01

    Postnatal mother-infant bonding refers to the early emotional bond between mothers and infants. Although some factors, such as maternal mental health, especially postnatal depression, have been considered in relation to mother-infant bonding, few studies have investigated the role of infant temperament traits in early bonding. In this study, the effects of maternal postnatal depressive and anxiety symptoms and infant temperament traits on mother-infant bonding were examined using both mother and father reports of infant temperament. Data for this study came from the first phase of the FinnBrain Birth Cohort Study (n=102, father reports n=62). After controlling for maternal symptoms of depression and anxiety, mother-reported infant positive emotionality, measured by infant smiling was related to better mother-infant bonding. In contrast, infant negative emotionality, measured by infant distress to limitations was related to lower quality of bonding. In regards to father-report infant temperament, only infant distress to limitations (i.e., frustration/anger) was associated with lower quality of mother-infant bonding. These findings underline the importance of infant temperament as one factor contributing to early parent-infant relationships, and counseling parents in understanding and caring for infants with different temperament traits. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. [Electrophysiological characteristics of hippocampal postnatal early development mediated by AMPA receptors in rats].

    PubMed

    Chen, Xue-Yi; Zhang, Ai-Feng; Zhao, Wen; Gao, Yu-Dan; Duan, Hong-Mei; Hao, Peng; Yang, Zhao-Yang; Li, Xiao-Guang

    2018-04-25

    The present study was aimed to investigate the electrophysiological characteristics of hippocampal postnatal early development mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rats. Forty-eight Wistar rats were divided into postnatal 0.5-, 1-, 2- and 3-month groups (n = 12). Spontaneous excitatory postsynaptic currents (sEPSCs) and field excitatory postsynaptic potentials (fEPSPs) mediated by AMPA receptors were recorded to evaluate the changes in the intrinsic membrane properties of hippocampal CA1 pyramidal neurons by using patch-clamp and MED64 planar microelectrode array technique respectively. The results showed that, during the period of postnatal 0.5-3 months, some of the intrinsic membrane properties of hippocampal CA1 pyramidal neurons, such as the membrane capacitance (Cm) and the resting membrane potential (RMP), showed no significant changes, while the membrane input resistance (Rin) and the time constant (τ) of the cells were decreased significantly. The amplitude, frequency and kinetics (both rise and decay times) of sEPSCs were significantly increased during the period of postnatal 0.5-1 month, but they were all decreased during the period of postnatal 1-3 months. In addition, the range of evoked fEPSPs in hippocamal CA1 region was significantly expanded, but the fEPSP amplitudes were decreased significantly during the period of postnatal 0.5-3 months. Furthermore, the evoked fEPSPs could be significantly inhibited by extracellular application of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These results suggest that AMPA receptor may act as a major type of excitatory receptor to regulate synaptic transmission and connections during the early stage of hippocampal postnatal development, which promotes the development and functional maturation of hippocampus in rats.

  1. Histological study on hippocampus, amygdala and cerebellum following low lead exposure during prenatal and postnatal brain development in rats.

    PubMed

    Barkur, Rajashekar Rao; Bairy, Laxminarayana K

    2016-06-01

    Neuropsychological studies in children who are exposed to lead during their early brain development have shown to develop behavioural and cognitive deficit. The aim of the present study was to assess the cellular damage in hippocampus, amygdala and cerebellum of rat pups exposed to lead during different periods of early brain development. Five groups of rat pups were investigated. (a) Control group (n = 8) (mothers of these rats were given normal drinking water throughout gestation and lactation), (b) pregestation lead-exposed group (n = 8) (mothers of these rats were exposed to 0.2% lead acetate in the drinking water for one month before conception), (c) gestation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout gestation [gestation day 01 to day 21]), (d) lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout lactation [postnatal day 01 to day 21]) and (e) gestation and lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate throughout gestation and lactation). On postnatal day 30, rat pups of all the groups were killed. Numbers of surviving neurons in the hippocampus, amygdala and cerebellum regions were counted using cresyl violet staining technique. Histological data indicate that lead exposure caused significant damage to neurons of hippocampus, amygdala and cerebellum regions in all lead-exposed groups except lactation lead-exposed group. The extent of damage to neurons of hippocampus, amygdala and cerebellum regions in lactation lead-exposed group was comparable to gestation and lactation groups even though the duration of lead exposure was much less in lactation lead-exposed group. To conclude, the postnatal period of brain development seems to be more vulnerable to lead neurotoxicity compared to prenatal period of brain development. © The Author(s) 2014.

  2. Early life exposure to traffic-related air pollution and allergic rhinitis in preschool children.

    PubMed

    Deng, Qihong; Lu, Chan; Yu, Yichen; Li, Yuguo; Sundell, Jan; Norbäck, Dan

    2016-12-01

    Evidence linking long-term exposure to outdoor air pollution with allergic rhinitis (AR) in children is scare, and the role of components of air pollution and timing of exposure remains unclear. To assess the association of pre- and post-natal exposure to air pollution with life-time prevalence of AR in preschool children. We conducted a cohort study of 2598 children aged 3-6 years in Changsha, China. The lifetime prevalence of AR was assessed by a questionnaire administered by parents. Children's exposures to dioxide nitrogen (NO 2 ), sulfur dioxide (SO 2 ) and particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) during different pre- and post-natal timing windows were estimated using the measured concentrations at monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of childhood AR for exposure to different air pollutants during different timing windows were assessed by logistic regression model in terms of an interquartile range (IQR) increase in exposure level. Life-time prevalence of AR in preschool children (7.3%) was associated with both pre- and post-natal exposure to traffic-related air pollution (TRAP), but only significant during the third trimester of pregnancy with adjusted OR = 1.40 (95% CI: 1.08-1.82) for a 15 μg/m 3 increase in NO 2 and during the first-year of life with adjusted OR = 1.36 (95% CI: 1.03-1.78) and 1.54 (95% CI: 1.07-2.21) respectively for 11 and 12 μg/m 3 increase in NO 2 and PM 10 . The association of early life exposure to TRAP with childhood AR was robust by adjusting for other air pollutants and timing windows. Sensitivity analysis indicated that the association was higher in the children who are male, young, with genetic predisposition by parental atopy, and living in damp houses. Early life exposure to traffic-related air pollutant during pregnancy and first-year of life may contribute to childhood AR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Adverse Associations of both Prenatal and Postnatal Exposure to Organophosphorous Pesticides with Infant Neurodevelopment in an Agricultural Area of Jiangsu Province, China

    PubMed Central

    Liu, Ping; Wu, Chunhua; Chang, Xiuli; Qi, Xiaojuan; Zheng, Minglan; Zhou, Zhijun

    2016-01-01

    Background: Prenatal exposure to organophosphorous (OP) pesticides has been found to be associated with adverse effects on child neurodevelopment, but evidence on potential effects induced by both prenatal and postnatal OP exposure in infants is limited. Objectives: Our aim was to investigate the associations of both prenatal and postnatal OP exposure with birth outcomes and infant neurodevelopment. Methods: Exposure to OP in 310 mother–infant pairs was assessed by measuring dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in urines from pregnant women and their children at 2 years of age. The Gesell Developmental Schedules was administered to examine neurodevelopment of 2-year-old children. Results: Based on the Gesell Developmental Schedules, the proportions of children with developmental delays were < 6%. Adverse associations between head circumference at birth and prenatal OP exposure were demonstrated. Both prenatal and postnatal OP exposure was significantly associated with increased risk of being developmentally delayed. Specifically, odds ratio (OR) value for prenatal DEs was 9.75 (95% CI: 1.28, 73.98, p = 0.028) in the adaptive area, whereas in the social area, OR values for postnatal DEs and DAPs were 9.56 (95% CI: 1.59, 57.57, p = 0.014) and 12.00 (95% CI: 1.23, 117.37, p = 0.033), respectively. Adverse associations were observed only in boys, not in girls. Conclusions: Both prenatal and postnatal OP exposure may adversely affect the neurodevelopment of infants living in the agricultural area. The present study adds to the accumulating evidence on associations of prenatal and postnatal OP exposure with infant neurodevelopment. Citation: Liu P, Wu C, Chang X, Qi X, Zheng M, Zhou Z. 2016. Adverse associations of both prenatal and postnatal exposure to organophosphorous pesticides with infant neurodevelopment in an agricultural area of Jiangsu Province, China. Environ Health Perspect 124:1637–1643; http

  4. Exposure to lipopolysaccharide in utero alters the postnatal metabolic response in heifers

    USDA-ARS?s Scientific Manuscript database

    This study was designed to determine the effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal metabolic response to an LPS challenge in beef heifers. Pregnant crossbred cows (n = 50) were assigned to a prenatal immune stimulation (PIS; n = 25; administered 0.1 micrograms/kg BW LPS s...

  5. Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

    PubMed Central

    Sun, Xiongshan; Han, Qi; Luo, Hongqin; Pan, Xiaodong; Ji, Yan; Yang, Yao; Chen, Hanying; Wang, Fangjie; Lai, Wenjing; Guan, Xiao; Zhang, Qi; Tang, Yuan; Chu, Jianhong; Yu, Jianhua; Shou, Weinian; Deng, Youcai; Li, Xiaohui

    2017-01-01

    Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition. PMID:28266538

  6. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    PubMed Central

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

  7. Effects of short-duration electromagnetic radiation on early postnatal neurogenesis in rats: Fos and NADPH-d histochemical studies.

    PubMed

    Orendáčová, Judita; Orendáč, Martin; Mojžiš, Miroslav; Labun, Ján; Martončíková, Marcela; Saganová, Kamila; Lievajová, Kamila; Blaško, Juraj; Abdiová, Henrieta; Gálik, Ján; Račeková, Eniko

    2011-11-01

    The immediate effects of whole body electromagnetic radiation (EMR) were used to study postnatal neurogenesis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of Wistar rats of both sexes. Newborn postnatal day 7 (P7) and young adult rats (P28) were exposed to pulsed electromagnetic fields (EMF) at a frequency of 2.45 GHz and mean power density of 2.8 mW/cm(2) for 2 h. Post-irradiation changes were studied using immunohistochemical localization of Fos and NADPH-d. We found that short-duration exposure induces increased Fos immunoreactivity selectively in cells of the SVZ of P7 and P28 rats. There were no Fos positive cells visible within the RMS of irradiated rats. These findings indicate that some differences exist in prerequisites of proliferating cells between the SVZ and RMS regardless of the age of the rats. Short-duration exposure also caused praecox maturation of NADPH-d positive cells within the RMS of P7 rats. The NADPH-d positive cells appeared several days earlier than in age-matched controls, and their number and morphology showed characteristics of adult rats. On the other hand, in the young adult P28 rats, EMR induced morphological signs typical of early postnatal age. These findings indicate that EMR causes age-related changes in the production of nitric oxide (NO), which may lead to different courses of the proliferation cascade in newborn and young adult neurogenesis. Copyright © 2010 Elsevier GmbH. All rights reserved.

  8. Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilities.

    PubMed

    Garcia, Stephanie J; Seidler, Frederic J; Slotkin, Theodore A

    2003-03-01

    The developmental neurotoxicity of the organophosphate pesticide chlorpyrifos (CPF) is thought to involve both neurons and glia, thus producing a prolonged window of vulnerability. To characterize the cell types and brain regions involved in these effects, we administered CPF to developing rats and examined neuroprotein markers for oligodendrocytes (myelin basic protein, MBP), for neuronal cell bodies (neurofilament 68 kDa, NF68), and for developing axons (neurofilament 200 kDa, NF200). Prenatal CPF administration on gestational days (GDs) 17-20 elicited an immediate (GD21) enhancement of MBP and NF68; by postnatal day (PN) 30, however, there were deficits in all three biomarkers, with the effect restricted to females. Exposure in the early postnatal period, PN1-4, did not evoke significant short-term or long-term changes in the neuroproteins. However, with treatment on PN11-14, we found reductions in MBP in the immediate posttreatment period (PN15, PN20) throughout the brain, and deficiencies across all three proteins emerged by PN30. With this regimen, males were targeted preferentially. The sex-selective effects seen here for the GD17-20 and PN11-14 regimens match those reported earlier for subsequent behavioral performance. These results indicate a shift in the populations of neural cells targeted by CPF, dependent upon the period of exposure. Similarly, developmental differences in the sex selectivity of the biochemical mechanisms underlying neurotoxicant actions are likely to contribute to discrete behavioral outcomes.

  9. Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep.

    PubMed

    Veiga-Lopez, Almudena; Moeller, Jacob; Sreedharan, Rohit; Singer, Kanakadurga; Lumeng, Carey; Ye, Wen; Pease, Anthony; Padmanabhan, Vasantha

    2016-02-01

    Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutaneous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy. Copyright © 2016 the American Physiological Society.

  10. Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep

    PubMed Central

    Veiga-Lopez, Almudena; Moeller, Jacob; Sreedharan, Rohit; Singer, Kanakadurga; Ye, Wen; Pease, Anthony

    2015-01-01

    Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutanous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy. PMID:26646100

  11. Exposure to fine and ultrafine particulate matter during gestation alters postnatal oligodendrocyte maturation, proliferation capacity, and myelination.

    PubMed

    Klocke, Carolyn; Allen, Joshua L; Sobolewski, Marissa; Blum, Jason L; Zelikoff, Judith T; Cory-Slechta, Deborah A

    2018-03-01

    Accumulating studies indicate that the brain is a direct target of air pollution exposure during the fetal period. We have previously demonstrated that exposure to concentrated ambient particles (CAPs) during gestation produces ventriculomegaly, periventricular hypermyelination, and enlargement of the corpus callosum (CC) during postnatal development in mice. This study aimed to further characterize the cellular basis of the observed hypermyelination and determine if this outcome, among other effects, persisted as the brain matured. Analysis of CC-1 + mature oligodendrocytes in the CC at postnatal days (PNDs) 11-15 suggest a premature maturational shift in number and proportion of total cells in prenatally CAPs-exposed males and females, with no overall change in total CC cellularity. The overall number of Olig2 + lineage cells in the CC was not affected in either sex at the same postnatal timepoint. Assessment of myelin status at early brain maturity (PNDs 57-61) revealed persistent hypermyelination in CAPs-exposed animals of both sexes. In addition, ventriculomegaly was persistent in CAPs-treated females, with possible amelioration of ventriculomegaly in CAPs-exposed males. When oligodendrocyte precursor cell (OPC) pool status was analyzed at PNDs 57-61, there were significant CAPs-induced alterations in cycling Ki67 + /Olig2 + cell number and proportion of total cells in the female CC. Total CC cellularity was slightly elevated in CAPs-exposed males at PNDs 57-61. Overall, these data support a growing body of evidence that demonstrate the vulnerability of the developing brain to environmental insults such as ambient particulate matter. The sensitivity of oligodendrocytes and myelin, in particular, to such an insult warrants further investigation into the mechanistic underpinnings of OPC and myelin disruption by constituent air pollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

    PubMed

    Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

    2018-03-01

    Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure.

    PubMed

    Ruggiero, M J; Boschen, K E; Roth, T L; Klintsova, A Y

    2018-06-01

    Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-α (TNF-α) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain.

  14. Prenatal and early postnatal depression and child maltreatment among Japanese fathers.

    PubMed

    Takehara, Kenji; Suto, Maiko; Kakee, Naoko; Tachibana, Yoshiyuki; Mori, Rintaro

    2017-08-01

    We investigated the association of paternal depression in the prenatal and early postnatal period with child maltreatment tendency at two months postpartum among Japanese fathers. This population-based longitudinal study recruited Japanese perinatal women and their partners living in Nishio City, Aichi, Japan. Of the 270 fathers who participated, 196 were included in the analysis. All data were collected via self-administrated questionnaires at four time points: 20 weeks' gestation and in the first few days, one month, and two months postpartum. Paternal depression was assessed using the Edinburgh Postnatal Depression Scale. Three definitions of paternal depression were coded based on participants' scores on this measure: prenatal, prior, and current. Child maltreatment tendency was evaluated using the Child Maltreatment Scale at two months postpartum. The associations of the three definitions of paternal depression and child maltreatment tendency were separately analyzed using logistic regression analysis. The prevalence of prenatal, prior, and current paternal depression was 9.7%, 10.2%, and 8.8%, respectively. According to the multivariate analysis, current paternal depression was significantly associated with child maltreatment tendency at two months postpartum (adjusted odds ratio: 7.77, 95% CI: 1.83-33.02). The other two types of depression, however, were not related to child maltreatment tendency. Thus, current paternal depression increased the risk of child maltreatment tendency in the postnatal period, suggesting that early detection and treatment of paternal depression might be useful for the prevention of child maltreatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

    PubMed Central

    Yang, Xiao-Dun; Liao, Xue-Mei; Uribe-Mariño, Andrés; Liu, Rui; Xie, Xiao-Meng; Jia, Jiao; Su, Yun-Ai; Li, Ji-Tao; Schmidt, Mathias V; Wang, Xiao-Dong; Si, Tian-Mei

    2015-01-01

    During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities. PMID:25403725

  16. Long term effects of PCBs (Phenoclor DP5) on rat microsomal enzymes, liver, and blood lipids after peri- and postnatal exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Poul, J.M.

    1992-02-01

    It was shown that activities of some hepatic drug metabolizing enzymes and parameters of lipid metabolism were modified in adult rats (PND100), after exposure to PCBs (Phenoclor DP5) during lactation. Perinatal or early postnatal treatment with inducers, like phenobarbital and phenytoin, seems to induce permanent effects on hepatic microsomal enzymes in adults though the drugs have completely disappeared from the body. Time course evolution of induction-related parameters and tissue residues of DP5, from weaning to PND100, have been studied the effects observed in adult rats at PND100 could be residual aspects of the important changes induced before weaning by acutemore » exposure via milk or consequences of the relative high concentrations of PCBs still present in tissues. The present study was designed to investigate the effects of DP5, administered peri- and postnatally, on microsomal enzyme activities and in vitro genotoxic activation of 2-aminofluorene and on liver and blood lipids, in adult rats at PND180 and PND300. Tissue residues of Phenoclor DP5 were measured in liver, fat and brain at the same periods.« less

  17. Early Life Stages

    EPA Pesticide Factsheets

    Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

  18. In utero exposure to lipopolysaccharide alters the postnatal acute phase response in beef heifers

    USDA-ARS?s Scientific Manuscript database

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

  19. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model.

    PubMed

    Hu, Jianzhong; Raikhel, Vincent; Gopalakrishnan, Kalpana; Fernandez-Hernandez, Heriberto; Lambertini, Luca; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Belpoggi, Fiorella; L Teitelbaum, Susan; Chen, Jia

    2016-06-14

    This proof-of-principle study examines whether postnatal, low-dose exposure to environmental chemicals modifies the composition of gut microbiome. Three chemicals that are widely used in personal care products-diethyl phthalate (DEP), methylparaben (MPB), triclosan (TCS)-and their mixture (MIX) were administered at doses comparable to human exposure to Sprague-Dawley rats from birth through adulthood. Fecal samples were collected at two time points: postnatal day (PND) 62 (adolescence) and PND 181 (adulthood). The gut microbiome was profiled by 16S ribosomal RNA gene sequencing, taxonomically assigned and assessed for diversity. Metagenomic profiling revealed that the low-dose chemical exposure resulted in significant changes in the overall bacterial composition, but in adolescent rats only. Specifically, the individual taxon relative abundance for Bacteroidetes (Prevotella) was increased while the relative abundance of Firmicutes (Bacilli) was reduced in all treated rats compared to controls. Increased abundance was observed for Elusimicrobia in DEP and MPB groups, Betaproteobacteria in MPB and MIX groups, and Deltaproteobacteria in TCS group. Surprisingly, these differences diminished by adulthood (PND 181) despite continuous exposure, suggesting that exposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescents. We also observed a small but consistent reduction in the bodyweight of exposed rats in adolescence, especially with DEP and MPB treatment (p < 0.05), which is consistent with our findings of a reduced Firmicutes/Bacteroidetes ratio at PND 62 in exposed rats. This study provides initial evidence that postnatal exposure to commonly used environmental chemicals at doses comparable to human exposure is capable of modifying the gut microbiota in adolescent rats; whether these changes lead to downstream health effects requires further investigation.

  20. Factors associated with early resumption of sexual intercourse among postnatal women in Uganda.

    PubMed

    Alum, Alice C; Kizza, Irene B; Osingada, Charles P; Katende, Godfrey; Kaye, Dan K

    2015-11-19

    Despite being a key component to be addressed during postnatal period, sexuality has long been a subject of secrecy and taboo in Africa. Resumption of sexual intercourse after giving birth has been shown to reduce extramarital affairs and consequently reduce risk of sexually transmitted infections like HIV/AIDS. Consequences of early resumption of sexual intercourse include unwanted pregnancy, genital trauma and puerperal infection. The objective of the study was to assess prevalence and factors associated with early resumption of sexual intercourse among postnatal mothers attending postnatal clinic at a National referral Hospital in Uganda. A cross-sectional study that employed an interviewer-administered questionnaire was conducted among 374 women who delivered six months prior to conducting the study. The independent variables included socio-demographic characteristics of the participant, socio-demographic characteristics of the spouse, perceived cultural norms, medical history, mode of delivery, and postpartum complications. The dependent variable was timing of resumption of sexual intercourse after childbirth (before or after six weeks postpartum). Data were analysed using SPSS version 16.0. The study showed that 105 participants (21.6%) had resumed sexual intercourse before 6 weeks after childbirth. The participants' education level, occupation, and parity; education level of the spouse, age of baby and use of family planning were the factors associated with early resumption of sexual intercourse after child birth (before six weeks postpartum) (p < 0.05). Many women resumed sexual intercourse after six weeks. Women with high income, low parity, who ever-used contraception or had a spouse with high education level were more likely to have early resumption of sexual intercourse.

  1. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

  2. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

    PubMed Central

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2014-01-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

  3. The Long-Term Economic Impact of in Utero and Postnatal Exposure to Malaria

    ERIC Educational Resources Information Center

    Barreca, Alan I.

    2010-01-01

    I use an instrumental-variables identification strategy and historical data from the United States to estimate the long-term economic impact of in utero and postnatal exposure to malaria. My research design matches adults in the 1960 Decennial Census to the malaria death rate in their respective state and year of birth. To address potential…

  4. High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission.

    PubMed

    Kuhn, Louise; Sinkala, Moses; Kankasa, Chipepo; Semrau, Katherine; Kasonde, Prisca; Scott, Nancy; Mwiya, Mwiya; Vwalika, Cheswa; Walter, Jan; Tsai, Wei-Yann; Aldrovandi, Grace M; Thea, Donald M

    2007-12-26

    Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024-0.055) than non-EBF infants (0.102 95% CI: 0.047-0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71-7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28-5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children's lives. ClinicalTrials.gov NCT00310726.

  5. Piracetam prevents memory deficit induced by postnatal propofol exposure in mice.

    PubMed

    Wang, Yuan-Lin; Li, Feng; Chen, Xin

    2016-05-15

    Postnatal propofol exposure impairs hippocampal synaptic development and memory. However, the effective agent to alleviate the impairments was not verified. In this study, piracetam, a positive allosteric modulator of AMPA receptor was administered following a seven-day propofol regime. Two months after propofol administration, hippocampal long-term potentiation (LTP) and long-term memory decreased, while intraperitoneal injection of piracetam at doses of 100mg/kg and 50mg/kg following last propofol exposure reversed the impairments of memory and LTP. Mechanically, piracetam reversed propofol exposure-induced decrease of BDNF and phosphorylation of mTor. Similar as piracetam, BDNF supplementary also ameliorated propofol-induced abnormalities of synaptic plasticity-related protein expressions, hippocampal LTP and long-term memory. These results suggest that piracetam prevents detrimental effects of propofol, likely via activating BDNF synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation

    EPA Science Inventory

    The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated ...

  7. Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity.

    PubMed

    Jiang, Yifei; Tong, Dongyi; Hofacer, Rylon D; Loepke, Andreas W; Lian, Qingquan; Danzer, Steve C

    2016-12-01

    Exposure to isoflurane increases apoptosis among postnatally generated hippocampal dentate granule cells. These neurons play important roles in cognition and behavior, so their permanent loss could explain deficits after surgical procedures. To determine whether developmental anesthesia exposure leads to persistent deficits in granule cell numbers, a genetic fate-mapping approach to label a cohort of postnatally generated granule cells in Gli1-CreER::GFP bitransgenic mice was utilized. Green fluorescent protein (GFP) expression was induced on postnatal day 7 (P7) to fate map progenitor cells, and mice were exposed to 6 h of 1.5% isoflurane or room air 2 weeks later (P21). Brain structure was assessed immediately after anesthesia exposure (n = 7 controls and 8 anesthesia-treated mice) or after a 60-day recovery (n = 8 controls and 8 anesthesia-treated mice). A final group of C57BL/6 mice was exposed to isoflurane at P21 and examined using neurogenesis and cell death markers after a 14-day recovery (n = 10 controls and 16 anesthesia-treated mice). Isoflurane significantly increased apoptosis immediately after exposure, leading to cell death among 11% of GFP-labeled cells. Sixty days after isoflurane exposure, the number of GFP-expressing granule cells in treated animals was indistinguishable from control animals. Rates of neurogenesis were equivalent among groups at both 2 weeks and 2 months after treatment. These findings suggest that the dentate gyrus can restore normal neuron numbers after a single, developmental exposure to isoflurane. The authors' results do not preclude the possibility that the affected population may exhibit more subtle structural or functional deficits. Nonetheless, the dentate appears to exhibit greater resiliency relative to nonneurogenic brain regions, which exhibit permanent neuron loss after isoflurane exposure.

  8. Effect of in utero wi-fi exposure on the pre- and postnatal development of rats.

    PubMed

    Poulletier de Gannes, Florence; Haro, Emmanuelle; Hurtier, Annabelle; Taxile, Murielle; Athane, Axel; Ait-Aissa, Saliha; Masuda, Hiroshi; Percherncier, Yann; Ruffié, Gilles; Billaudel, Bernard; Dufour, Philippe; Veyret, Bernard; Lagroye, Isabelle

    2012-04-01

    The increase in exposure to the Wireless Fidelity (Wi-Fi) wireless communication signal has raised public health concerns especially for young people. Animal studies looking at the effects of early life and prenatal exposure to this source of electromagnetic fields, in the radiofrequency (RF) range, on development and behavior have been considered as high priority research needs by the World Health Organization. For the first time, our study assessed the effects of in utero exposure to a 2450 MHz Wi-Fi signal (2 hr/day, 6 days/week for 18 days) on pregnant rats and their pups. Three levels in terms of whole-body specific absorption rate were used: 0.08, 0.4, and 4 W/kg. The prenatal study on fetuses delivered by caesarean (P20) concerned five females/group. The dams and their offspring were observed for 28 days after delivery (15 females/group). For all test conditions, no abnormalities were noted in the pregnant rats and no significant signs of toxicity were observed in the pre- and postnatal development of the pups, even at the highest level of 4 W/kg. In the present study, no teratogenic effect of repeated exposures to the Wi-Fi wireless communication signal was demonstrated even at the highest level of 4 W/kg. The results from this screening study aimed at investigating Wi-Fi effects, strengthen the previous conclusions that teratology and development studies have not detected any noxious effects of exposures to mobile telephony-related RF fields at exposure levels below standard limits. © 2012 Wiley Periodicals, Inc.

  9. Oligodendrocytes as Regulators of Neuronal Networks during Early Postnatal Development

    PubMed Central

    Ramos, Maria; Ikrar, Taruna; Kinoshita, Chisato; De Mei, Claudia; Tirotta, Emanuele; Xu, Xiangmin; Borrelli, Emiliana

    2011-01-01

    Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development. PMID:21589880

  10. CONSEQUENCES OF REPEATED ETHANOL EXPOSURE DURING EARLY OR LATE ADOLESCENCE ON CONDITIONED TASTE AVERSIONS IN RATS

    PubMed Central

    Saalfield, Jessica; Spear, Linda

    2015-01-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences.. Recent evidence suggests that adolescents are less sensitive than adults to ethanol’s aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25%) or water every 48 hours from postnatal day (P) 25–45 (early AIE) or P45–65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. PMID:25698309

  11. The developmental neurotoxicity of arsenic: cognitive and behavioral consequences of early life exposure.

    PubMed

    Tolins, Molly; Ruchirawat, Mathuros; Landrigan, Philip

    2014-01-01

    More than 200 million people worldwide are chronically exposed to arsenic. Arsenic is a known human carcinogen, and its carcinogenic and systemic toxicity have been extensively studied. By contrast, the developmental neurotoxicity of arsenic has been less well described. The aim of this review was to provide a comprehensive review of the developmental neurotoxicity of arsenic. We reviewed the published epidemiological and toxicological literature on the developmental neurotoxicity of arsenic. Arsenic is able to gain access to the developing brain and cause neurotoxic effects. Animal models link prenatal and early postnatal exposure to reduction in brain weight, reductions in numbers of glia and neurons, and alterations in neurotransmitter systems. Animal and in vitro studies both suggest that oxidative stress may be a mechanism of arsenic neurotoxicity. Fifteen epidemiological studies indicate that early life exposure is associated with deficits in intelligence and memory. These effects may occur at levels of exposure below current safety guidelines, and some neurocognitive consequences may become manifest only later in life. Sex, concomitant exposures, and timing of exposure appear to modify the developmental neurotoxicity of arsenic. Four epidemiological studies failed to show behavioral outcomes of arsenic exposure. The published literature indicates that arsenic is a human developmental neurotoxicant. Ongoing and future prospective birth cohort studies will allow more precise definition of the developmental consequences of arsenic exposure in early life. Copyright © 2014. Published by Elsevier Inc.

  12. The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol.

    PubMed

    Jones, Eleanor; Taylor, Beck; MacArthur, Christine; Pritchett, Ruth; Cummins, Carole

    2016-02-08

    The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health-related outcomes. A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current

  13. Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

    PubMed

    Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

    2017-09-01

    The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Associations between prenatal and childhood PBDE exposure and early adolescent visual, verbal and working memory.

    PubMed

    Cowell, Whitney J; Margolis, Amy; Rauh, Virginia A; Sjödin, Andreas; Jones, Richard; Wang, Ya; Garcia, Wanda; Perera, Frederica; Wang, Shuang; Herbstman, Julie B

    2018-05-19

    Prenatal and childhood exposure to polybrominated diphenyl ether (PBDE) flame retardants has been inversely associated with cognitive performance, however, few studies have measured PBDE concentrations in samples collected during both prenatal and postnatal periods. We examined prenatal (cord) and childhood (ages 2, 3, 5, 7 and 9 years) plasma PBDE concentrations in relation to memory outcomes assessed between the ages of 9 and 14 years. The study sample includes a subset (n = 212) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used multivariable linear regression to examine associations between continuous log 10 -transformed PBDE concentrations and performance on tests of visual, verbal and working memory in age-stratified models. We additionally used latent class growth analysis to estimate trajectories of exposure across early life, which we analyzed as a categorical variable in relation to memory outcomes. We examined interactions between PBDE exposure and sex using cross-product terms. Associations between prenatal exposure and working memory significantly varied by sex (p-interaction = 0.02), with inverse relations observed only among girls (i.e. β BDE-47  = -7.55, 95% CI: -13.84, -1.24). Children with sustained high concentrations of BDEs-47, 99 or 100 across childhood scored approximately 5-8 standard score points lower on tests of visual memory. Children with PBDE plasma concentrations that peaked during toddler years performed better on verbal domains, however, these associations were not statistically significant. Exposure to PBDEs during both prenatal and postnatal periods may disrupt memory domains in early adolescence. These findings contribute to a substantial body of evidence supporting the developmental neurotoxicity of PBDEs and underscore the need to reduce exposure among pregnant women and children. Copyright © 2018

  15. Associations between prenatal and recent postnatal methylmercury exposure and auditory function at age 19 years in the Seychelles Child Development Study.

    PubMed

    Orlando, Mark S; Dziorny, Adam C; Harrington, Donald; Love, Tanzy; Shamlaye, Conrad F; Watson, Gene E; van Wijngaarden, Edwin; Davidson, Philip W; Myers, Gary J

    2014-01-01

    The aim of this study was to determine if prenatal or recent postnatal methylmercury (MeHg) exposure from consuming ocean fish and seafood is associated with auditory deficits in young adults. Some investigators have reported adverse associations while others have found no associations. Ocean fish is an important nutrient source for billions of people around the world. Consequently, determining if there is an adverse association with objective auditory measures is important in assessing whether a risk is present or not. The peripheral and central auditory function of 534 subjects in the Seychelles Child Development Study (SCDS) Main Cohort was examined at age of 19 years. The auditory test battery included standard pure-tone audiometry, tympanometry, auditory brainstem response (ABR) latencies, and both click-evoked and distortion product otoacoustic emissions (OAE). Associations with MeHg were evaluated with multiple linear regression models, adjusting for sex, recent postnatal MeHg exposure, and hearing loss. Bilateral hearing loss (defined as a mean pure-tone threshold of greater than 25 dB) was present in 1.1%of the subjects and was not associated with prenatal or recent postnatal MeHg exposure. As expected, absolute and interwave ABR latencies were shorter for women as compared to men, as the stimulus presentation rate decreased from 69.9 to 19.9 clicks/s and as the stimulus intensity increased from 60 to 80 dBnHL. Similarly, larger OAE amplitudes were elicited in women as compared to men and in the right ears as compared to the left. There was no association of prenatal MeHg exposure with hearing loss, ABR absolute and interwave latencies or OAE amplitudes. As recent postnatal MeHg increased, some associations were found with a few ABR absolute and interwave latencies and a few OAE amplitudes. However, the direction of these associations was inconsistent. As recent postnatal MeHg levels increased the wave I absolute latencies were shorter at 80 dBnHL for all

  16. The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.

    PubMed

    Perkins, Amy E; Fadel, Jim R; Kelly, Sandra J

    2015-05-01

    Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability

  17. A missense mutation in myosin VIIA prevents aminoglycoside accumulation in early postnatal cochlear hair cells.

    PubMed

    Richardson, G P; Forge, A; Kros, C J; Marcotti, W; Becker, D; Williams, D S; Thorpe, J; Fleming, J; Brown, S D; Steel, K P

    1999-11-28

    Myosin VIIA is expressed by sensory hair cells in the inner ear and proximal tubule cells in the kidney, the two primary targets of aminoglycoside antibiotics. Using cochlear cultures prepared from early postnatal Myo7a6J mice with a missense mutation in the head region of the myosin VIIA molecule we show that this myosin is required for aminoglycoside accumulation in cochlear hair cells. Hair cells in homozygous mutant Myo7a6J cochlear cultures have disorganized hair bundles, but are otherwise morphologically normal and transduce. However, and in contrast to hair cells from heterozygous Myo7a6J cultures, the homozygous Myo7a6J hair cells do not accumulate [3H]gentamicin and do not exhibit an ototoxic response on exposure to aminoglycoside. Possible roles for myosin VIIA in the process of aminoglycoside accumulation are discussed.

  18. Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers.

    PubMed

    Modabbernia, A; Velthorst, E; Gennings, C; De Haan, L; Austin, C; Sutterland, A; Mollon, J; Frangou, S; Wright, R; Arora, M; Reichenberg, A

    2016-08-01

    Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb(2+)), manganese (Mn(2+)), cadmium (Cd(2+)), copper (Cu(2+)), magnesium (Mg(2+)), and zinc (Zn(2+)), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. We found higher early-life Pb(2+) exposure among patients with schizophrenia than controls. The differences in log Mn(2+) and log Cu(2+) changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb(2+) levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb(2+) levels and adult IQ. In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Intervention among new parents followed up by an interview study exploring their experiences of telemedicine after early postnatal discharge.

    PubMed

    Danbjørg, D B; Wagner, L; Kristensen, B R; Clemensen, J

    2015-06-01

    a move towards earlier postnatal discharge raises the challenge of finding new ways to support families when they are discharged early after childbirth. to explore how postnatal parents experienced the use of telemedicine following early discharge from hospital (i.e. 24 hours after childbirth) by investigating if they consider that their postnatal needs are met, and whether or not they experience a sense of security and parental self-efficacy. intervention followed by a qualitative interview study. The intervention took place on a postnatal ward with approximately 1000 births a year. An app including chat, a knowledgebase and automated messages was trialled between postnatal parents at home and the hospital. Parents had access to the app for seven days after discharge. 42 new mothers were recruited from the postnatal ward in accordance with the inclusion criteria (i.e. discharged within 24 hours of childbirth). Both parents were invited for interview. 42 sets of parents participated in the trial, and 28 sets agreed to be interviewed. Interviews (n=28) were conducted with 27 mothers and 11 fathers. Parents were interviewed together in 10 cases, 17 mothers were interviewed alone, and one father was interviewed alone. The data analysis was inspired by systematic text condensation based on Giorgi׳s descriptive phenomenological method. parents were confident in use of the app, and did not experience any barriers in contacting the nurses via asynchronous communication. Parents received timely information and guidance by communicating online, and felt that their follow-up support needs were met. parents viewed the app as a lifeline, and saw it as a means of informing and guiding them following early discharge from hospital after childbirth. As such, this app shows potential for enhancing self-efficacy and postnatal sense of security. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Neurobehavioral effects of postnatal exposure to low-level mercury vapor and/or methylmercury in mice.

    PubMed

    Yoshida, Minoru; Lee, Jin-Yong; Satoh, Masahiko; Watanabe, Chiho

    2018-01-01

    This study examined the effects on neurobehavioral function of exposure to low-level mercury vapor (Hg 0 ), methylmercury (MeHg) in female mice and the combination of Hg 0 and MeHg during postnatal development. Postnatal mice were exposed to Hg 0 at a mean concentration of 0.188 mg/m 3 Hg 0 and supplied with food containing 3.85 μg/g of MeHg from day 2 to day 28 after delivery. The combined exposure group was exposed to both Hg 0 and MeHg, using the same procedure. When their offspring reached the age of 11 weeks, behavioral analyses were performed. The behavioral effects in mice were evaluated based on locomotive activity and rate of center entries in the open field (OPF), learning activity in the passive avoidance response (PA) and spatial learning ability in the radial maze (RM). Total locomotive activity in the OPF significantly decreased in the Hg 0 , MeHg and combined exposure groups compared with the control group. The proportion of entries to central area in the OPF was significantly higher in the combined exposure group than in the control group, while those in the Hg 0 or MeHg exposure group did not differ from the control group. Other behavioral tests did not reveal significant differences among the groups. Behavioral anomalies were more distinctive after combined exposure compared to Hg 0 or MeHg exposure alone. The brain Hg concentration of offspring, immediately after exposure, was highest in the combined exposure group, exceeding 2 μg/g, followed by the MeHg and Hg 0 exposure groups. Thus, the enhancement of neurobehavioral effects in the combined exposure group was associated with higher brain mercury concentration.

  1. Recurrence quantification analysis to characterize cyclical components of environmental elemental exposures during fetal and postnatal development

    PubMed Central

    Austin, Christine; Gennings, Chris; Tammimies, Kristiina; Bölte, Sven; Arora, Manish

    2017-01-01

    Environmental exposures to essential and toxic elements may alter health trajectories, depending on the timing, intensity, and mixture of exposures. In epidemiologic studies, these factors are typically analyzed as a function of elemental concentrations in biological matrices measured at one or more points in time. Such an approach, however, fails to account for the temporal cyclicity in the metabolism of environmental chemicals, which if perturbed may lead to adverse health outcomes. Here, we conceptualize and apply a non-linear method–recurrence quantification analysis (RQA)–to quantify cyclical components of prenatal and early postnatal exposure profiles for elements essential to normal development, including Zn, Mn, Mg, and Ca, and elements associated with deleterious health effects or narrow tolerance ranges, including Pb, As, and Cr. We found robust evidence of cyclical patterns in the metabolic profiles of nutrient elements, which we validated against randomized twin-surrogate time-series, and further found that nutrient dynamical properties differ from those of Cr, As, and Pb. Furthermore, we extended this approach to provide a novel method of quantifying dynamic interactions between two environmental exposures. To achieve this, we used cross-recurrence quantification analysis (CRQA), and found that elemental nutrient-nutrient interactions differed from those involving toxicants. These rhythmic regulatory interactions, which we characterize in two geographically distinct cohorts, have not previously been uncovered using traditional regression-based approaches, and may provide a critical unit of analysis for environmental and dietary exposures in epidemiological studies. PMID:29112980

  2. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

    PubMed Central

    Malloul, Hanaa; Mahdani, Ferdaousse M.; Bennis, Mohammed; Ba-M’hamed, Saadia

    2017-01-01

    Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice (N = 21) were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1), offspring (N = 88) length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were revealed only in the

  3. Melamine in prenatal and postnatal organs in rats.

    PubMed

    Chu, Ching Yan; Chu, Kai On; Ho, Chung Shun; Kwok, Sung Shing; Chan, Ho Ming; Fung, Kwok Pui; Wang, Chi Chiu

    2013-01-01

    Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding. In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats. Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages. Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood. Distribution of melamine in all postnatal organs was higher than that in prenatal organs. Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs. It may relate to the high vulnerability to the toxicity of melamine in this population. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy.

    PubMed

    Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

    2016-03-01

    To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy.I n the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment.

  5. Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy

    PubMed Central

    Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

    2016-01-01

    Abstract To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy. In the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment. PMID:26945416

  6. Behavioral alterations induced in rats by a pre- and postnatal exposure to 2,4-dichlorophenoxyacetic acid.

    PubMed

    Bortolozzi, A A; Duffard, R O; Evangelista de Duffard, A M

    1999-01-01

    The purpose of this study was to determine whether the behavioral development pattern was altered by a pre- and postnatal exposure to 2,4-Dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postnatal day (PND) 23. After weaning, the pups were assigned to one of the two subgroups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Effects on offsprings were evaluated with a neurotoxicological test battery. Neuromotor reflexes, spontaneous motor activity, serotonin syndrome, circling, and catalepsy were analyzed during various postnatal ages. 2,4-D neonatal exposure induced delay of the ontogeny of righting reflex and negative geotaxis accompanied by motor abnormalities, stereotypic behaviors (excessive grooming and vertical head movements), and hyperactivity in the open field. Adult rats of both sexes (T2 group) showed a diminution of ambulation and rearing, while excessive grooming responses were only observed in T2 males. Besides, these animals manifested serotonin syndrome behaviors, catalepsy, and right-turning preference. Some behaviors were reversible, but others were permanent, and some were only expressed after pharmacological challenges.

  7. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

    PubMed

    Saalfield, Jessica; Spear, Linda

    2015-12-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth

    PubMed Central

    Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

    2013-01-01

    Background We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4–7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4–7 years, as well as height and head circumference at 4–7 years of age, were the exposure variables. Z-scores of weight at 4–7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child’s IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4–18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Results Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18–2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06–0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4–7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth

  9. Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth.

    PubMed

    Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

    2013-02-01

    We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4-7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4-7 years, as well as height and head circumference at 4-7 years of age, were the exposure variables. Z-scores of weight at 4-7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child's IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4-18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18-2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06-0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4-7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth measures were associated with IQ or

  10. MEAL PARAMETERS AND VAGAL GASTROINTESTINAL AFFERENTS IN MICE THAT EXPERIENCED EARLY POSTNATAL OVERNUTRITION

    PubMed Central

    Biddinger, Jessica E.; Fox, Edward A.

    2010-01-01

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component - the vagus nerve - has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal-size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 hour/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. PMID:20403369

  11. Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

    PubMed

    Biddinger, Jessica E; Fox, Edward A

    2010-08-04

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats.

    PubMed

    Pinto, Bruno Araújo Serra; Melo, Thamys Marinho; Flister, Karla Frida Torres; França, Lucas Martins; Kajihara, Daniela; Tanaka, Leonardo Yuji; Laurindo, Francisco Rafael Martins; Paes, Antonio Marcus de Andrade

    2016-08-01

    Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.

  13. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    PubMed

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Effects of prenatal and postnatal parent depressive symptoms on adopted child HPA regulation: independent and moderated influences.

    PubMed

    Laurent, Heidemarie K; Leve, Leslie D; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Harold, Gordon T; Reiss, David

    2013-05-01

    This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents' symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk.

  15. S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice.

    PubMed

    Ornoy, Asher; Weinstein-Fudim, Liza; Tfilin, Matanel; Ergaz, Zivanit; Yanai, Joseph; Szyf, Moshe; Turgeman, Gadi

    2018-01-16

    A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight. From day 50, we carried out neurobehavioral tests and assessment of the antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT activity, lipid peroxidation and the expression of antioxidant genes. Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that were more prominent in males. Changes in the activity of SOD and CAT increased lipid peroxidation and changes in the expression of antioxidant genes were observed in the prefrontal cortex of VPA treated mice, more prominent in females, while ASD like behavior was more prominent in males. There were no changes in the redox potential of the liver. The co-administration of VPA and SAM alleviated most ASD like neurobehavioral symptoms and normalized the redox potential in the prefrontal cortex. Early postnatal VPA administration induces ASD like behavior that is more severe in males, while the redox status changes are more severe in females; SAM corrects both. VPA-induced ASD seems to result from epigenetic changes, while the redox status changes may be secondary. Copyright © 2018. Published by Elsevier Inc.

  16. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    PubMed

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock. © 2014 Wiley Periodicals, Inc.

  17. Postnatal chlorpyrifos exposure and apolipoprotein E (APOE) genotype differentially affect cholinergic expression and developmental parameters in transgenic mice.

    PubMed

    Basaure, Pia; Guardia-Escote, Laia; Cabré, Maria; Peris-Sampedro, Fiona; Sánchez-Santed, Fernando; Domingo, José L; Colomina, Maria Teresa

    2018-05-03

    Chlorpyrifos (CPF) is one of the most commonly used organophosphate pesticides in the world. Our previous results described that apolipoprotein E (APOE) polymorphisms are a source of individual differences in susceptibility to CPF. The aim of this study was to assess the physical and biochemical effects of postnatal exposure to CPF in the apoE targeted replacement mouse model. Mice were exposed to CPF at 0 or 1 mg/kg/day from postnatal day 10-15. Physical development, plasma and forebrain cholinesterase (ChE) activity and gene expression in liver and forebrain were evaluated. CPF exposure delays physical maturation and decreases the expression of choline acetyltransferase, α4-subunit and the α7 receptor. CPF decreases the expression of vesicular acetylcholine transporter (VAChT) mRNA in the forebrain only in apoE3 mice. The expression of paraoxonase-2 in the forebrain was also influenced by APOE genotype and CPF. Differences between genotypes were observed in litter size, ChE activity, expression of butyrylcholinesterase and paraoxonase-1 in liver and variants of acetylcholinesterase, VAChT and the α7 receptor in the forebrain. These results support that there are different vulnerabilities to postnatal CPF exposure according to the APOE polymorphism, which in turn affects the cholinergic system and defenses to oxidative stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Postnatal development and behavior effects of in-utero exposure of rats to radiofrequency waves emitted from conventional WiFi devices.

    PubMed

    Othman, Haifa; Ammari, Mohamed; Rtibi, Kaïs; Bensaid, Noura; Sakly, Mohsen; Abdelmelek, Hafedh

    2017-06-01

    The present work investigated the effects of prenatal exposure to radiofrequency waves of conventional WiFi devices on postnatal development and behavior of rat offspring. Ten Wistar albino pregnant rats were randomly assigned to two groups (n=5). The experimental group was exposed to a 2.45GHz WiFi signal for 2h a day throughout gestation period. Control females were subjected to the same conditions as treated group without applying WiFi radiations. After delivery, the offspring was tested for physical and neurodevelopment during its 17 postnatal days (PND), then for anxiety (PND 28) and motricity (PND 40-43), as well as for cerebral oxidative stress response and cholinesterase activity in brain and serum (PND 28 and 43). Our main results showed that the in-utero WiFi exposure impaired offspring neurodevelopment during the first seventeen postnatal days without altering emotional and motor behavior at adult age. Besides, prenatal WiFi exposure induced cerebral oxidative stress imbalance (increase in malondialdehyde level (MDA) and hydrogen peroxide (H 2 O 2 ) levels and decrease in catalase (CAT) and superoxide dismutase (SOD) activities) at 28 but not 43days old, also the exposure affected acethylcolinesterase activity at both cerebral and seric levels. Thus, the current study revealed that maternal exposure to WiFi radiofrequencies led to various adverse neurological effects in the offspring by affecting neurodevelopment, cerebral stress equilibrium and cholinesterase activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. [Formation of antioxidant defence system of geese in embryogenesis and early postnatal ontogenesis].

    PubMed

    Danchenko, O O; Kalytka, V V

    2002-01-01

    The features of antioxidant protection of tissues of a liver and blood of the gooses in embriogenesis and early postnatal ontogenesis are found out. Maximal contents TBA active products both in a liver, and in a blood are observed in 28 diurnal embriones. Is shown, that in a liver the activity of basic antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) in a liver is developed already at early stages embriogenesis and is considerably enlarged in the end embriogenesis. The becoming of enzymatic system of a blood descends much more slower.

  20. Postnatal proteasome inhibition induces neurodegeneration and cognitive deficiencies in adult mice: a new model of neurodevelopment syndrome.

    PubMed

    Romero-Granados, Rocío; Fontán-Lozano, Ángela; Aguilar-Montilla, Francisco Javier; Carrión, Ángel Manuel

    2011-01-01

    Defects in the ubiquitin-proteasome system have been related to aging and the development of neurodegenerative disease, although the effects of deficient proteasome activity during early postnatal development are poorly understood. Accordingly, we have assessed how proteasome dysfunction during early postnatal development, induced by administering proteasome inhibitors daily during the first 10 days of life, affects the behaviour of adult mice. We found that this regime of exposure to the proteasome inhibitors MG132 or lactacystin did not produce significant behavioural or morphological changes in the first 15 days of life. However, towards the end of the treatment with proteasome inhibitors, there was a loss of mitochondrial markers and activity, and an increase in DNA oxidation. On reaching adulthood, the memory of mice that were injected with proteasome inhibitors postnatally was impaired in hippocampal and amygdala-dependent tasks, and they suffered motor dysfunction and imbalance. These behavioural deficiencies were correlated with neuronal loss in the hippocampus, amygdala and brainstem, and with diminished adult neurogenesis. Accordingly, impairing proteasome activity at early postnatal ages appears to cause morphological and behavioural alterations in adult mice that resemble those associated with certain neurodegenerative diseases and/or syndromes of mental retardation.

  1. Neonatal nicotine exposure alters leptin signaling in the hypothalamus-pituitary-thyroid axis in the late postnatal period and adulthood in rats.

    PubMed

    Santos-Silva, A P; Moura, E G; Pinheiro, C R; Rios, A S; Abreu-Villaça, Y; Passos, M C F; Oliveira, E; Lisboa, P C

    2010-07-31

    Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus-pituitary-thyroid axis of suckling and adult offspring. Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p<0.05. In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (-61%, -42%, -56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (-52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (-44%, -50%, -47%) and higher pSTAT-3 expression (+80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+1.54x) and lower pSTAT-3 content (-34%). Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Role of postnatal dietary sodium in prenatally programmed hypertension.

    PubMed

    Stewart, Tyrus; Ascani, Jeannine; Craver, Randall D; Vehaskari, V Matti

    2009-09-01

    In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43-49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal "reprogramming" of the hypertension.

  3. Effects of early exposure to phthalates and bisphenols on cardiometabolic outcomes in pregnancy and childhood.

    PubMed

    Philips, Elise M; Jaddoe, Vincent W V; Trasande, Leonardo

    2017-03-01

    Pregnant women are exposed to various chemicals, including endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenols. Increasing evidence suggests that early life exposures to phthalates and bisphenols may contribute to cardiometabolic risks. The aim of this narrative review was to summarize current knowledge of the effects of fetal and childhood exposure to phthalates and bisphenols on child growth and child cardiometabolic outcomes and the effects on maternal outcomes. In total, 54 studies were identified and included. The majority of studies found effects of phthalates and bisphenols on maternal, child growth, and cardiometabolic outcomes. Currently results suggest that early life exposure to phthalates and bisphenols may have a substantial influence on perinatal and postnatal cardiometabolic programming. In a large part of the investigated outcomes studies show contradictory results. However, the majority of the existing evidence is based on non-cohort studies with single samples neglecting time-variant effects and complicating conclusions regarding causal inference. More studies are needed investigating the mechanisms and its potential interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Growth trajectories in early childhood, their relationship with antenatal and postnatal factors, and development of obesity by age 9 years: results from an Australian birth cohort study.

    PubMed

    Giles, L C; Whitrow, M J; Davies, M J; Davies, C E; Rumbold, A R; Moore, V M

    2015-07-01

    In an era where around one in four children in the United Kingdom, the United States, and Australia are overweight or obese, the development of obesity in early life needs to be better understood. We aimed to identify groups of children with distinct trajectories of growth in infancy and early childhood, to examine any association between these trajectories and body size at age 9, and to assess the relative influence of antenatal and postnatal exposures on growth trajectories. Prospective Australian birth cohort study. In total, 557 children with serial height and weight measurements from birth to 9 years were included in the study. Latent class growth models were used to derive distinct groups of growth trajectories from birth to age 3½ years. Multivariable logistic regression models were used to explore antenatal and postnatal predictors of growth trajectory groups, and multivariable linear and logistic regression models were used to examine the relationships between growth trajectory groups and body size at age 9 years. We identified four discrete growth trajectories from birth to age 3½ years, characterised as low, intermediate, high, or accelerating growth. Relative to the intermediate growth group, the low group had reduced z-body mass index (BMI) (-0.75 s.d.; 95% confidence interval (CI) -1.02, -0.47), and the high and accelerating groups were associated with increased body size at age 9 years (high: z-BMI 0.70 s.d.; 95% CI 0.49, 0.62; accelerating: z-BMI 1.64 s.d.; 95% CI 1.16, 2.11). Of the antenatal and postnatal exposures considered, the most important differentiating factor was maternal obesity in early pregnancy, associated with a near quadrupling of risk of membership of the accelerating growth trajectory group compared with the intermediate growth group (odds ratio (OR) 3.72; 95% CI 1.15, 12.05). Efforts to prevent childhood obesity may need to be embedded within population-wide strategies that also pay attention to healthy weight for women in

  5. Early life exposure to 2.45GHz WiFi-like signals: effects on development and maturation of the immune system.

    PubMed

    Sambucci, Manolo; Laudisi, Federica; Nasta, Francesca; Pinto, Rosanna; Lodato, Rossella; Lopresto, Vanni; Altavista, Pierluigi; Marino, Carmela; Pioli, Claudio

    2011-12-01

    The development of the immune system begins during embryogenesis, continues throughout fetal life, and completes its maturation during infancy. Exposure to immune-toxic compounds at levels producing limited/transient effects in adults, results in long-lasting or permanent immune deficits when it occurs during perinatal life. Potentially harmful radiofrequency (RF) exposure has been investigated mainly in adult animals or with cells from adult subjects, with most of the studies showing no effects. Is the developing immune system more susceptible to the effects of RF exposure? To address this question, newborn mice were exposed to WiFi signals at constant specific absorption rates (SAR) of 0.08 or 4 W/kg, 2h/day, 5 days/week, for 5 consecutive weeks, starting the day after birth. The experiments were performed with a blind procedure using sham-exposed groups as controls. No differences in body weight and development among the groups were found in mice of both sexes. For the immunological analyses, results on female and male newborn mice exposed during early post-natal life did not show any effects on all the investigated parameters with one exception: a reduced IFN-γ production in spleen cells from microwaves (MW)-exposed (SAR 4 W/kg) male (not in female) mice compared with sham-exposed mice. Altogether our findings do not support the hypothesis that early post-natal life exposure to WiFi signals induces detrimental effects on the developing immune system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Clinical presentation of postnatal and non-postnatal depressive episodes.

    PubMed

    Cooper, Carly; Jones, Lisa; Dunn, Emma; Forty, Liz; Haque, Sayeed; Oyebode, Femi; Craddock, Nick; Jones, Ian

    2007-09-01

    The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.

  7. Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

    PubMed

    Marasco, Valeria; Spencer, Karen A; Robinson, Jane; Herzyk, Pawel; Costantini, David

    2013-09-15

    Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Effects of Prenatal and Postnatal Parent Depressive Symptoms on Adopted Child HPA Regulation: Independent and Moderated Influences

    PubMed Central

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Harold, Gordon T.; Reiss, David

    2013-01-01

    This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents’ symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk. PMID:22686176

  9. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    PubMed

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P < 0.001) and length ( P < 0.04) compared with controls and was associated with significantly reduced plasma levels of mouse GH ( P < 0.01) and IGF-1 ( P < 0.01). RhGH abrogated these hypoxia-induced changes of the GH/IGF-1 axis associated with normalization of weight and length gain until P14 compared with controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

  10. Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

    PubMed

    Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

    2014-10-01

    Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity. © 2014 Society for Endocrinology.

  11. Influence of prenatal and postnatal exposure to passive smoking on infants' health during the first six months of their life.

    PubMed

    Kukla, L; Hrubá, D; Tyrlík, M

    2004-09-01

    On the Czech set of European Longitudinal Study of Pregnancy and Childhood (ELSPAC), we tried to verify whether it is possible to confirm the results of foreign studies which found out that the both prenatal and postnatal exposure of newborns to chemicals on cigarette smoke could influence the newborns' morbidity in the first six months of their life. Mothers, who served as sources of data about their smoking behaviour during the pregnancy and after the birth as well as information about the health status of the children after the birth (N=3,871) were divided into four groups: 1. women who never smoked (74.3%), 2. women who stopped smoking in pregnancy and started to smoke after delivery (18.3%), 3. women who smoked both during pregnancy and after delivery (7.2%), 4. women who smoked during pregnancy and stopped after delivery. Unfortunatelly, the last group was very small (only seven mothers) and did not allow assessment of exclusively prenatal exposition. Sucklings from Czech ELSPAC set exposed to chemicals in cigarette smoke either only after the birth or also during the prenatal period, showed significantly higher occurence of different symptoms of respiratory tract damages and their complications (like otitis media) when compared to children of non smoking mothers. Due to illnesses during the first six months after the birth, their parents had to look more often for the consultations of physician, including hospitalization. Our results, as well as results of foreign studies, confirm, that smoking of mothers during the pregnancy and after the birth represents significant risk for the first months of life. Illnesses of children in this early period can cause longitudinal consequences which emerge during the childhood as well as in adulthood. They also represent a strong stressogenic factor. Children's health consequences of exposure to cigarette smoke request very often intensive and expensive care within health system. Our results are the same as those of

  12. Update on Postnatal Steroids.

    PubMed

    Halliday, Henry L

    2017-01-01

    Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment

  13. Effects of noise exposure on neonatal auditory brainstem response thresholds in pregnant guinea pigs at different gestational periods.

    PubMed

    Morimoto, Chihiro; Nario, Kazuhiko; Nishimura, Tadashi; Shimokura, Ryota; Hosoi, Hiroshi; Kitahara, Tadashi

    2017-01-01

    Noise exposure during pregnancy has been reported to cause fetal hearing impairment. However, little is known about the effects of noise exposure during various gestational stages on postnatal hearing. In the present study, we investigated the effects of noise exposure on auditory brainstem response (ABR) at the early, mid-, and late gestational periods in newborn guinea pigs. Pregnant guinea pigs were exposed to 4-kHz pure tone at a 120-dB sound pressure level for 4 h. We divided the animals into four groups as follows: the control, early gestational exposure, mid-gestational exposure, and late gestational exposure groups. ABR thresholds and latencies in newborns were recorded using 1-, 2-, and 4-kHz tone burst on postnatal days 1, 7, 14, and 28. Changes in ABR thresholds and latencies were measured between the 4 × 4 and 4 × 3 factorial groups mentioned above (gestational periods × postnatal days, gestational periods × frequencies). The thresholds were low in the order of control group < early gestational exposure group < mid-gestational exposure group and late gestational exposure group. Noise exposure during pregnancy influenced ABR thresholds in neonatal guinea pigs. This is the first study to show that noise exposure during the early, mid-, and late gestational periods significantly elevated ABR thresholds in neonatal guinea pigs. © 2016 Japan Society of Obstetrics and Gynecology.

  14. The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning.

    PubMed

    Li, Ki Angel; Lund, Emilie Torp; Voigt, Jörg-Peter W

    2016-01-01

    The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post-natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non-maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Risk profiles associated with postnatal depressive symptoms among women in a public sector hospital in Mexico: the role of sociodemographic and psychosocial factors.

    PubMed

    de Castro, Filipa; Place, Jean Marie S; Billings, Deborah L; Rivera, Leonor; Frongillo, Edward A

    2015-06-01

    This study examined the association between postnatal depressive symptoms and a set of demographic and psychosocial factors among 604 women attending a public hospital for postnatal care in Mexico City. Specific profiles of women that would indicate an increased probability for developing postnatal depression (PND) based on discrete combinations of risk and protective factors were generated. In a logistic model, followed by the estimation of predicted probabilities, we examined the association between depressive symptomatology and psychosocial factors: low social support, unplanned pregnancies, history of depression, and exposure to moderate or severe intimate partner violence (IPV) during pregnancy. Postnatal depressive symptomatology was reported by 10.6 % of the women, as measured by scores at 12 or above on the Edinburgh Postnatal Depression Scale. The cumulative probability of presenting PND in the simultaneous presence of the psychosocial factors was 67.0 %; however, this could be reduced to 5.5 % through preventive measures that work to eliminate low social support, unplanned pregnancy, and exposure to severe IPV during pregnancy. Early identification of psychosocial risk factors, specifically low social support, unplanned pregnancies, history of depression, and exposure to violence during pregnancy, is recommended.

  16. Amelioration of cerebellar dysfunction in rats following postnatal ethanol exposure using low-intensity pulsed ultrasound.

    PubMed

    Bolbanabad, Hiva Mohammadi; Anvari, Enayat; Rezai, Mohammad Jafar; Moayeri, Ardashir; Kaffashian, Mohammad Reza

    2017-04-01

    The neonatal development stage of the cerebellum in rats is equivalent to a human foetus in the third trimester of pregnancy. In this stage, cell proliferation, migration, differentiation, and synaptogenesis occur. Clinical and experimental findings have shown that ethanol exposure during brain development causes a variety of disruptions to the brain, including neurogenesis depression, delayed neuronal migration, changes in neurotransmitter synthesis, and neuronal depletion.During postnatal cerebellar development, neurons are more vulnerable to the destructive effects of ethanol. The effects of low-intensity pulsed ultrasound (LIPUS) on the number of cells and thickness of the cell layers within the cerebellar cortex were examined during the first two postnatal weeks in rats following postnatal ethanol exposure. Postpartum rats were distributed randomly into six groups. Normal saline was injected intraperitoneally into control animals and ethanol (20%) was injected into the intervention groups for three consecutive days. Intervention groups received LIPUS at different frequencies (3 or 5MHz), after administration of ethanol. After transcardial perfusion, the rat's brain was removed, and a complete series of sagittal cerebellum sections were obtained by systematic random manner. Photomicrographs were made with Motic digital cameras and analysed using Nikon digital software. The numbers of granular cells decreased in ethanol-treated rats compared to the control group. LIPUS, administered at (3 or 5MHz), combined with ethanol administration resulted in a reduction of ethanol's effects. Using 5MHz LIPUS resulted in significantly higher numbers of granular cells in the internal layer compared to the control rats. Using 3 or 5MHz LIPUS alone resulted in a significant enhancement in the granular cells of the molecular layer. A significant reduction was seen in the thickness of the external granular layer in ethanol-treated rats. This study showed that exposure to LIPUS

  17. Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

    PubMed

    Martin, J H; Donarummo, L; Hacking, A

    2000-02-01

    This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous

  18. Exposure to dim light at night during early development increases adult anxiety-like responses.

    PubMed

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  19. Relative importance of prenatal and postnatal androgen action in determining growth of the penis and anogenital distance in the rat before, during and after puberty.

    PubMed

    van den Driesche, S; Scott, H M; MacLeod, D J; Fisken, M; Walker, M; Sharpe, R M

    2011-12-01

    Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p < 0.0001). However, altered endogenous androgen exposure may confound interpretation of changes in adults exposed prenatally/postnatally to DBP/flutamide. We conclude that AGD provides a lifelong guide to prenatal androgen exposure (in the MPW) whereas penis size reflects both prenatal + postnatal androgen exposure. At

  20. Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

    PubMed

    Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

    2015-08-01

    Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  1. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice.

    PubMed

    Allen, Joshua L; Liu, Xiufang; Pelkowski, Sean; Palmer, Brian; Conrad, Katherine; Oberdörster, Günter; Weston, Douglas; Mayer-Pröschel, Margot; Cory-Slechta, Deborah A

    2014-09-01

    Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. We observed brain region- and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air

  2. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytesmore » and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.« less

  3. The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants.

    PubMed

    Porcelli, Peter J; Weaver, R Grey

    2010-06-01

    Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. Evaluate relationship between early postnatal nutriture and ROP surgery. Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Early postnatal GFAP-expressing cells produce multilineage progeny in cerebrum and astrocytes in cerebellum of adult mice.

    PubMed

    Guo, Zhibao; Wang, Xijuan; Xiao, Jun; Wang, Yihui; Lu, Hong; Teng, Junfang; Wang, Wei

    2013-09-26

    Early postnatal GFAP-expressing cells are thought to be immature astrocytes. However, it is not clear if they possess multilineage capacity and if they can generate different lineages (astrocytes, neurons and oligodendrocytes) in the brain of adult mice. In order to identify the fate of astroglial cells in the postnatal brain, hGFAP-Cre-ER(T2) transgenic mice were crossed with the R26R Cre reporter mouse strains which exhibit constitutive expression of β-galactosidase (β-gal). Mice carrying the hGFAP-Cre-ER(T2)/R26R transgene were treated with Tamoxifen to induce Cre recombination in astroglial cells at postnatal (P) day 6 and Cre recombinase-expressing cells were identified by X-gal staining. Immunohistochemical staining was used to identify the type(s) of these reporter-tagged cells. Sixty days after recombination, X-gal-positive cells in different cerebral regions of the adult mice expressed the astroglial markers Blbp and GFAP, the neuronal marker NeuN, the oligodendrocyte precursor cell marker NG2 and the mature oligodendrocyte marker CC1. X-gal-positive cells in the cerebellum coexpressed the astroglial marker Blbp, but not the granule cell marker NeuN, Purkinje cell marker Calbindin or oligodendrocyte precursor cell marker NG2. Our genetic fate mapping data demonstrated that early postnatal GFAP-positive cells possessed multilineage potential and eventually differentiated into neurons, astrocytes, and oligodendrocyte precursor cells in the cerebrum and into astrocytes (including Bergmann glia) in the cerebellum of adult mice. © 2013 Elsevier B.V. All rights reserved.

  5. Transient postnatal fluoxetine leads to decreased brain arachidonic acid metabolism and cytochrome P450 4A in adult mice.

    PubMed

    Ramadan, Epolia; Blanchard, Helene; Cheon, Yewon; Fox, Meredith A; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I; Basselin, Mireille

    2014-05-01

    Fetal and perinatal exposure to selective serotonin (5-HT) reuptake inhibitors (SSRIs) has been reported to alter childhood behavior, while transient early exposure in rodents is reported to alter their behavior and decrease brain extracellular 5-HT in adulthood. Since 5-HT2A/2C receptor-mediated neurotransmission can involve G-protein coupled activation of cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (ARA) from synaptic membrane phospholipid, we hypothesized that transient postnatal exposure to fluoxetine would alter brain ARA metabolism in adult mice. Brain ARA incorporation coefficients k* and rates Jin were quantitatively imaged following intravenous [1-(14)C]ARA infusion of unanesthetized adult mice that had been injected daily with fluoxetine (10mg/kg i.p.) or saline during postnatal days P4-P21. Expression of brain ARA metabolic enzymes and other relevant markers also was measured. On neuroimaging, k* and Jin was decreased widely in early fluoxetine- compared to saline-treated adult mice. Of the enzymes measured, cPLA2 activity was unchanged, while Ca(2+)-independent iPLA2 activity was increased. There was a significant 74% reduced protein level of cytochrome P450 (CYP) 4A, which can convert ARA to 20-HETE. Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. These changes might contribute to reported altered behavior following early SSRI in rodents. Published by Elsevier Ltd.

  6. Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

    PubMed

    Nakanishi, S T; Whelan, P J

    2010-05-01

    During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

  7. Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during Adulthood

    PubMed Central

    McDonald, Fiona B.; Dempsey, Eugene M.; O'Halloran, Ken D.

    2016-01-01

    Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life. PMID:26973537

  8. Behavioral Effects of Pre- and Postnatal Exposure to Smoking, Alcohol, and Caffeine in 5-Month-Old Infants.

    ERIC Educational Resources Information Center

    Dowler, Jeffrey K.; Jacobson, Sandra W.

    This study examined the behavioral effects of prenatal and postnatal exposure to smoking, alcohol, and caffeinated beverages on 5-month-old infants. The sample consisted of 179 Caucasian infants and their mothers. All mothers were 19 years of age or older and had at least a tenth-grade education. Mental and motor portions of the Bayley Scales of…

  9. Cumulative Exposure to Cell-Free HIV in Breast Milk, Rather Than Feeding Pattern per se, Identifies Postnatally Infected Infants

    PubMed Central

    Neveu, Dorine; Viljoen, Johannes; Bland, Ruth M.; Nagot, Nicolas; Danaviah, Siva; Coutsoudis, Anna; Rollins, Nigel Campbell; Coovadia, Hoosen M.; Van de Perre, Philippe; Newell, Marie-Louise

    2011-01-01

    Background. We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure. Methods. Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern. Results. Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ∼15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 106 copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001). Conclusions. Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants. PMID:21367736

  10. Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review

    PubMed Central

    2015-01-01

    Purpose Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Methods Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Results Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Conclusion Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development. PMID:25996151

  11. Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review.

    PubMed

    Kingston, Dawn; McDonald, Sheila; Austin, Marie-Paule; Tough, Suzanne

    2015-01-01

    Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development.

  12. Post-natal myogenic and adipogenic developmental

    PubMed Central

    Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten MG; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom

    2011-01-01

    A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNAGT−/−) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. PMID:21818413

  13. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blossom, Sarah J., E-mail: blossomsarah@uams.edu; Cooney, Craig A.; Melnyk, Stepan B.

    2013-06-15

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers ofmore » oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced

  14. Early gestational exposure to moderate concentrations of ethanol alters adult behaviour in C57BL/6J mice.

    PubMed

    Sanchez Vega, Michelle C; Chong, Suyinn; Burne, Thomas H J

    2013-09-01

    Alcohol consumption during pregnancy has deleterious effects on the developing foetus ranging from subtle physical deficits to severe behavioural abnormalities and is encompassed under a broad umbrella term, foetal alcohol spectrum disorders (FASD). High levels of exposure show distinct effects, whereas the consequences of moderate exposures have been less well studied. The aim of this study was to examine the effects of a moderate dose ethanol exposure using an ad libitum drinking procedure during the first eight days of gestation in mice on the behavioural phenotype of adult offspring. Adult female C57Bl/6J mice were mated and exposed to either 10% (v/v) ethanol or water for the first 8 days of gestation (GD 0-8), and then offered water for the rest of gestation. Early developmental milestone achievement was assessed in offspring at postnatal days (P) 7, 14 and 21. Adult offspring underwent a comprehensive battery of behavioural tests to examine a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception, as well as spatial memory in a water maze. Ethanol-exposed mice had similar postnatal developmental trajectories to water-exposed mice. However, the ethanol-exposed mice showed increased hyperlocomotion at P 14, 21 and 70 (p<0.05). Increased exploration and heightened motivation were also observed in adult mice. Furthermore, ethanol-exposed mice showed a significant improvement in memory in the water maze. The main findings were that mice had persistent and long lasting alterations in behaviour, including hyperactivity and enhanced spatial memory. These data suggest that even moderate dose ethanol exposure in early gestation has long term consequences on brain function and behaviour in mice. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  15. Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity.

    PubMed

    Slidsborg, Carina; Jensen, Louise Bering; Rasmussen, Steen Christian; Fledelius, Hans Callø; Greisen, Gorm; Cour, Morten de la

    2018-01-01

    To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex). Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Oral methylphenidate alleviates the fine motor dysfunction caused by chronic postnatal manganese exposure in adult rats.

    PubMed

    Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R

    2015-04-01

    Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. 1H magnetic resonance spectroscopy metabolite profiles of neonatal rat hippocampus and brainstem regions following early postnatal exposure to intermittent hypoxia

    NASA Astrophysics Data System (ADS)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor

    2017-03-01

    Most premature infants born at less than 30 weeks gestation are exposed to periods of mild intermittent hypoxia (IH) associated with apnea of prematurity and periodic breathing. In adults, IH associated with sleep apnea causes neurochemical and structural alterations in the brain. However, it is unknown whether IH in the premature infant leads to neurodevelopmental impairment. Quantification of biochemical markers that can precisely identify infants at risk of adverse neurodevelopmental outcome is essential. In vivo 1H magnetic resonance spectroscopy (1H MRS) facilitates the quantification of metabolites from distinct regions of the developing brain. We report the changes in metabolite profiles in the brainstem and hippocampal regions of developing rat brains, resulting from exposure to IH. Rat pups were chosen for study because there is rapid postnatal hippocampal development that occurs during the first 4 weeks in the developing rat brain, which corresponds to the first 2-3 postnatal years of development in humans. The brainstem was examined because of our interest in respiratory control disorders in the newborn and because of brainstem gliosis described in infants who succumb to Sudden Infant Death Syndrome (SIDS). Metabolite profiles were compared between hypoxia treated rat pups (n = 9) and normoxic controls (n = 6). Metabolite profiles were acquired using the Point-RESolved spectroscopy (PRESS) MRS sequence and were quantified using the TARQUIN software. There was a significant difference in the concentrations of creatine (p = 0.031), total creatine (creatine + phosphocreatine) (p = 0.028), and total choline (p = 0.001) in the brainstem, and glycine (p = 0.031) in the hippocampal region. The changes are consistent with altered cellular bioenergetics and metabolism associated with hypoxic insult.

  18. Sex differences in the consequences of early-life exposure to epidemiological stress--a life-history approach.

    PubMed

    Störmer, Charlotte

    2011-01-01

    Exposure to infectious disease in early life has been suggested to have a negative effect on later-life survival,possibly through the induction of inflammatory responses. Although a life-course perspective emphasizes the importance of both survival and reproduction for individual fitness, to date, no studies have investigated whether early-life exposure to infectious disease has an impact on reproduction as it has been suggested for later survival. To address this question, I have used family reconstitution data from a historical (18th and 19th century) human population in the Krummhörn (Germany) comparing survival and reproduction between an exposed and a non-exposed group. The exposed group comprised those exposed to a high-infectious disease load during prenatal and early postnatal development. The results show a marked sex difference in the impact of early-life exposure to infectious disease. Exposed females show no effect on their life expectancy but significantly reduced fertility (number of children). For exposed males, however, the effect on survival is opponent over time: mortality is increased during childhood but decreased in late adulthood. Above that, exposed males reproduce earlier and have a smaller proportion of surviving children. This study does not support former studies indicating a negative association between early-life disease load and later survival. I argue that due to differences in male and female life strategies, males in general are more vulnerable especially early in life. Hence, adverse environmental conditions may have a stronger effect on male survivability and reproductive performance.

  19. Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood

    PubMed Central

    Huang, Lianyan; Yang, Guang

    2014-01-01

    Background Recent studies in rodents suggest that repeated and prolonged anesthetic exposure at early stages of development leads to cognitive and behavioral impairments later in life. However, the underlying mechanism remains unknown. In this study, we tested whether exposure to general anesthesia during early development will disrupt the maturation of synaptic circuits and compromise learning-related synaptic plasticity later in life. Methods Mice received ketamine/xylazine (20/3 mg/kg) anesthesia for one or three times, starting at either early [postnatal day 14 (P14)] or late (P21) stages of development (n=105). Control mice received saline injections (n=34). At P30, mice were subjected to rotarod motor training and fear conditioning. Motor learning-induced synaptic remodeling was examined in vivo by repeatedly imaging fluorescently-labeled postsynaptic dendritic spines in the primary motor cortex before and after training using two-photon microscopy. Results Three exposures to ketamine/xylazine anesthesia between P14–18 impair the animals’ motor learning and learning-dependent dendritic spine plasticity [new spine formation, 8.4 ± 1.3% (mean ± SD) versus 13.4 ± 1.8%, P = 0.002] without affecting fear memory and cell apoptosis. One exposure at P14 or three exposures between P21–25 has no effects on the animals’ motor learning or spine plasticity. Finally, enriched motor experience ameliorates anesthesia-induced motor learning impairment and synaptic deficits. Conclusion Our study demonstrates that repeated exposures to ketamine/xylazine during early development impair motor learning and learning-dependent dendritic spine plasticity later in life. The reduction in synaptic structural plasticity may underlie anesthesia-induced behavioral impairment. PMID:25575163

  20. Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice☆

    PubMed Central

    Basgen, John M.; Sobin, Christina

    2014-01-01

    Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) μg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) μg/dL]. Higher-level lead exposed mice [14.68 (2.74) μg/dL] had no change in either glomerular volume or podocyte number. The increase in glomerular volume was explained by increases in glomerular capillary and mesangial volumes with no change in podocyte volume. Early chronic lead exposure yielding very low blood lead levels alters glomerular development in pre-adolescent animals. PMID:24300173

  1. Physical, behavioral, and cognitive effects of prenatal tobacco and postnatal secondhand smoke exposure.

    PubMed

    Zhou, Sherry; Rosenthal, David G; Sherman, Scott; Zelikoff, Judith; Gordon, Terry; Weitzman, Michael

    2014-09-01

    The purpose of this review is to examine the rapidly expanding literature regarding the effects of prenatal tobacco and postnatal secondhand smoke (SHS) exposure on child health and development. Mechanisms of SHS exposure are reviewed, including critical periods during which exposure to tobacco products appears to be particularly harmful to the developing fetus and child. The biological, biochemical, and neurologic effects of the small fraction of identified components of SHS are described. Research describing these adverse effects of both in utero and childhood exposure is reviewed, including findings from both animal models and humans. The following adverse physical outcomes are discussed: sudden infant death syndrome, low birth weight, decreased head circumference, respiratory infections, otitis media, asthma, childhood cancer, hearing loss, dental caries, and the metabolic syndrome. In addition, the association between the following adverse cognitive and behavioral outcomes and such exposures is described: conduct disorder, attention-deficit/hyperactivity disorder, poor academic achievement, and cognitive impairment. The evidence supporting the adverse effects of SHS exposure is extensive yet rapidly expanding due to improving technology and increased awareness of this profound public health problem. The growing use of alternative tobacco products, such as hookahs (a.k.a. waterpipes), and the scant literature on possible effects from prenatal and secondhand smoke exposure from these products are also discussed. A review of the current knowledge of this important subject has implications for future research as well as public policy and clinical practice. Published by Mosby, Inc.

  2. Regional Myelin and Axon Damage and Neuroinflammation in the Adult Mouse Brain After Long-Term Postnatal Vanadium Exposure.

    PubMed

    Azeez, Idris A; Olopade, Funmilayo; Laperchia, Claudia; Andrioli, Anna; Scambi, Ilaria; Onwuka, Silas K; Bentivoglio, Marina; Olopade, James O

    2016-09-01

    Environmental exposure to vanadium occurs in areas of persistent burning of fossil fuels; this metal is known to induce oxidative stress and oligodendrocyte damage. Here, we determined whether vanadium exposure (3 mg/kg) in mice during the first 3 postnatal months leads to a sustained neuroinflammatory response. Body weight monitoring, and muscle strength and open field tests showed reduction of body weight gain and locomotor impairment in vanadium-exposed mice. Myelin histochemistry and immunohistochemistry for astrocytes, microglia, and nonphosphorylated neurofilaments revealed striking regional heterogeneity. Myelin damage involved the midline corpus callosum and fibers in cortical gray matter, hippocampus, and diencephalon that were associated with axonal damage. Astrocyte and microglial activation was identified in the same regions and in the internal capsule; however, no overt myelin and axon damage was observed in the latter. Double immunofluorescence revealed induction of high tumor necrosis factor (TNF) immunoreactivity in reactive astrocytes. Western blotting analysis showed significant induction of TNF and interleukin-1β expression. Together these findings show that chronic postnatal vanadium exposure leads to functional deficit and region-dependent myelin damage that does not spare axons. This injury is associated with glial cell activation and proinflammatory cytokine induction, which may reflect both neurotoxic and neuroprotective responses. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  3. Developmental programming: postnatal estradiol amplifies ovarian follicular defects induced by fetal exposure to excess testosterone and dihydrotestosterone in sheep.

    PubMed

    Veiga-Lopez, A; Wurst, A K; Steckler, T L; Ye, W; Padmanabhan, V

    2014-04-01

    Excess of prenatal testosterone (T) induces reproductive defects including follicular persistence. Comparative studies with T and dihydrotestosterone (DHT) have suggested that follicular persistence is programmed via estrogenic actions of T. This study addresses the androgenic and estrogenic contributions in programming follicular persistence. Because humans are exposed to estrogenic environmental steroids from various sources throughout their life span and postnatal insults may also induce organizational and/or activational changes, we tested whether continuous postnatal exposure to estradiol (E) will amplify effects of prenatal steroids on ovarian function. Pregnant sheep were treated with T, DHT, E, or ED (E and DHT) from days 30 to 90 of gestation. Postnatally, a subset of the vehicle (C), T, and DHT females received an E implant. Transrectal ultrasonography was performed in the first breeding season during a synchronized cycle to monitor ovarian follicular dynamics. As expected, number of ≥8 mm follicles was higher in the T versus C group. Postnatal E reduced the number of 4 to 8 mm follicles in the DHT group. Percentage of females bearing luteinized follicles and the number of luteinized follicles differed among prenatal groups. Postnatal E increased the incidence of subluteal cycles in the prenatal T-treated females. Findings from this study confirm previous findings of divergences in programming effects of prenatal androgens and estrogens. They also indicate that some aspects of follicular dynamics are subject to postnatal modulation as well as support the existence of an extended organizational period or the need for a second insult to uncover the previously programmed event.

  4. Exposure to genocide and the risk of schizophrenia: a population-based study.

    PubMed

    Levine, S Z; Levav, I; Goldberg, Y; Pugachova, I; Becher, Y; Yoffe, R

    2016-03-01

    No evidence exists on the association between genocide and the incidence of schizophrenia. This study aims to identify critical periods of exposure to genocide on the risk of schizophrenia. This population-based study comprised of all subjects born in European nations where the Holocaust occurred from 1928 to 1945, who immigrated to Israel by 1965 and were indexed in the Population Register (N = 113 932). Subjects were followed for schizophrenia disorder in the National Psychiatric Case Registry from 1950 to 2014. The population was disaggregated to compare groups that immigrated before (indirect exposure: n = 8886, 7.8%) or after (direct exposure: n = 105 046, 92.2%) the Nazi or fascist era of persecutions began. The latter group was further disaggregated to examine likely initial prenatal or postnatal genocide exposures. Cox regression modelling was computed to compare the risk of schizophrenia between the groups, adjusting for confounders. The likely direct group was at a statistically (p < 0.05) greater risk of schizophrenia (hazard ratio = 1.27, 95% confidence interval 1.06-1.51) than the indirect group. Also, the likely combined in utero and postnatal, and late postnatal (over age 2 years) exposure subgroups were statistically at greater risk of schizophrenia than the indirect group (p < 0.05). The likely in utero only and early postnatal (up to age 2 years) exposure subgroups compared with the indirect exposure group did not significantly differ. These results were replicated across three sensitivity analyses. This study showed that genocide exposure elevated the risk of schizophrenia, and identified in utero and postnatal (combined) and late postnatal (age over 2 years) exposures as critical periods of risk.

  5. Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

    PubMed

    Murphy, Margaret O; Herald, Joseph B; Wills, Caleb T; Unfried, Stanley G; Cohn, Dianne M; Loria, Analia S

    2017-02-01

    Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P < 0.05). Also, HFD increased plasma corticosterone (196 ± 51 vs. 79 ± 18 pg/ml, P < 0.05) and leptin levels (1.8 ± 0.4 vs. 1.3 ± 0.1 ng/ml, P < 0.05) in female MatSep compared with control rats, whereas insulin and adiponectin levels were similar between groups. Female control and MatSep offspring were treated with MTP (50 µg/g ip) 30 min before the daily separation. MTP treatment significantly attenuated diet-induced obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease. Copyright © 2017 the American Physiological

  6. Early post-natal neuroactive steroid manipulation modulates ondansetron effects on initial periods of alcohol consumption in rats.

    PubMed

    Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc

    2018-06-21

    Neuroactive steroids (NS) such as allopregnanolone are crucial for brain development and adult behaviour. Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses, an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels. The aim of the present study is to observe if the effects of the 5HT3 receptor antagonist ondansetron on initial alcohol consumption are modulated by post-natal NS manipulation. For this purpose, allopregnanolone, finasteride, or vehicle was injected from day 5 to 9. In adulthood, a novel object preference test was carried out in order to detect a possible novelty-seeking pattern in our animals, which has been related to vulnerability to drug abuse. The subjects then had access to two bottles (alcohol or control solutions) one hour daily for two consecutive weeks. Ondansetron (0.01 mg/kg, 0.1 mg/kg or vehicle) was administered before the hour of consumption in the initial phase (days 1, 2, 3) of the procedure, and after prolonged alcohol intake (days 11, 12, 13). Results indicated that finasteride animals showed a higher preference to explore the new object, as well as a higher alcohol consumption than the rest of the groups. Moreover, 0.1 mg/kg of ondansetron decreased alcohol consumption, but only in the post-natal finasteride group, suggesting a possible increase in 5HT3 receptor sensitivity in these animals. In conclusion, NS manipulation in crucial stages of development, such as early post-natal periods, seems to play an important role on the effects of ondansetron on alcohol intake and in the vulnerability to develop drug use or abuse. Copyright © 2018. Published by Elsevier Inc.

  7. In utero and postnatal exposure to a phytoestrogen-enriched diet increases parameters of acute inflammation in a rat model of TNBS-induced colitis.

    PubMed

    Seibel, Jan; Molzberger, Almut F; Hertrampf, Torsten; Laudenbach-Leschowski, Ute; Degen, Gisela H; Diel, Patrick

    2008-12-01

    Inflammatory bowel disease (IBD) is very common in Europe and USA. Its incidence in East Asia has been traditionally low, albeit the risk of IBD increases in Asian immigrants adopting western lifestyles, suggesting a strong role of environmental/dietary factors in IBD. A lifelong exposure to phytoestrogen-rich diets has been associated with a decreased risk of developing breast cancer and might also be protective against IBD. We studied the influence of in utero and postnatal exposure to a phytoestrogen (PE)-rich diet on acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were exposed in utero and postnatally to high (genistein: 240 microg/g feed; daidzein: 232 microg/g feed) or very low levels (genistein and daidzein <10 microg/g feed) of phytoestrogen isoflavones fed to pregnant dams with the diet and throughout nursing. After weaning, the offspring had free access to these diets. At the age of 11 weeks, colitis was induced with an enema of TNBS. After 3 days, animals were sacrificed and tissues were collected for histological evaluation and analysis of molecular markers of inflammation. Animals kept on a PE-rich diet (PRD) had higher colon weights than animals on low PE-levels (PDD), suggesting enhanced acute inflammation by phytoestrogens. This result was supported by histological findings and by analysis of myeloperoxidase activity. Interestingly, relative mRNA and protein expression of cyclooxygenase-2 (COX-2) were modulated in rats on PRD, providing evidence that COX-2, the inducible isoform of the enzyme, is involved in the management of colonic inflammation. Our results suggest that early-in-life exposure to PE might not protect against the development of IBD but enhances the extent of acute inflammation.

  8. The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure.

    PubMed

    Herbison, Carly E; Allen, Karina; Robinson, Monique; Newnham, John; Pennell, Craig

    2017-10-01

    There is debate about the relative importance of timing of stressful events prenatally and over the life course and risk for subsequent depressive/anxious illness. The aim of this study was to examine the relative roles of prenatal stress and postnatal stress trajectories in predicting depression and anxiety in early adulthood in males and females. Exposure to life stress events was examined in the Western Australian Pregnancy Cohort (Raine) Study during pregnancy and ages 1, 2, 3, 5, 8, 10, 14, and 17 years. At age 20, offspring completed the Depression Anxiety Stress Scale. Prenatal stress and trajectories of stress events from age 1 to 17 were analyzed in linear regression analyses. Five postnatal stress trajectories were identified. In females, medium to high chronic stress exposure or exposure during puberty/adolescence predicted depression and anxiety symptoms while low or reduced stress exposure over the life course did not, after adjustment for relevant confounders. High stress early in pregnancy contributed to male depression/anxiety symptoms independent of postnatal stress trajectory. In females, postnatal stress trajectory was more important than prenatal stress in predicting depression/anxiety symptoms. Interventions focused on reducing and managing stress events around conception/pregnancy and exposure to chronic stress are likely to have beneficial outcomes on rates of depression and anxiety in adults.

  9. Manipulation of pre and postnatal androgen environments and anogenital distance in rats.

    PubMed

    Kita, Diogo H; Meyer, Katlyn B; Venturelli, Amanda C; Adams, Rafaella; Machado, Daria L B; Morais, Rosana N; Swan, Shanna H; Gennings, Chris; Martino-Andrade, Anderson J

    2016-08-10

    We examined the anogenital distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13-20 with vehicle, flutamide (20mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750mg/kg/day), or testosterone (1.0mg/kg/day). After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days 23-53. In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats. Postnatal flutamide, DEHP, and testosterone induced slight but significant reductions in male AGD. Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero, although it can also be slightly responsive to changes in the androgen environment following pubertal exposure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development.

    PubMed

    Lin, Yanfen; Xu, Jian; Huang, Jun; Jia, Yinan; Zhang, Jinsong; Yan, Chonghuai; Zhang, Jun

    2017-01-01

    Maternal stress is associated with impairments in the neurodevelopment of offspring; however, the effects of the timing of exposure to maternal stress on a child's neurodevelopment are unclear. In 2010, we studied 225 mother-child pairs in Shanghai, recruiting mothers in mid-to-late pregnancy and monitoring offspring from birth until 30 months of age. Maternal stress was assessed prenatally (at 28-36 weeks of gestation) and postnatally (at 24-30 months postpartum) using the Symptom-Checklist-90-Revised Scale (SCL-90-R) and Life-Event-Stress Scale to evaluate mothers' emotional stress and life event stress levels, respectively. Children's cognition and temperament were assessed at 24-30 months of age using the Gesell Development Scale and Toddler Temperament Scale, respectively. Multi-variable linear regression models were used to associate prenatal and postnatal stress with child cognitive and temperamental development. Maternal prenatal and postnatal Global Severity Index (GSI) of SCL-90-R were moderately correlated (ICC r=0.30, P<0.001). After adjusting for relevant covariates, the increase in prenatal GSI was associated with decreases in toddlers' gross motor, fine motor, adaptive and social behavior development independently of postnatal GSI, while the increase in postnatal GSI was associated with changes in multiple temperament dimensions independently of prenatal GSI. The effects of prenatal and postnatal depression scores of SCL-90-R were similar to those of GSI. Relatively small sample size. Compared with postnatal exposure, children's cognitive development may be more susceptible to prenatal exposure to maternal emotional stress, whereas temperamental development may be more affected by postnatal exposure to maternal emotional stress compared with prenatal exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Developmental disruption of medial prefrontal cortical GABAergic function by non-contingent cocaine exposure during early adolescence

    PubMed Central

    Cass, Daryn K.; Thomases, Daniel R.; Caballero, Adriana; Tseng, Kuei Y.

    2013-01-01

    Background Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further our understanding on the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts the overall medial prefrontal cortex (mPFC) network function in adulthood. Methods A non-contingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days -PD- 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacological manipulations. Results Cocaine exposure during early adolescence yields a distinctive hyper-metabolic PFC state that was not observed in adult (PD75-80)-treated rats. Local field potential recordings expand upon these findings by showing that early adolescent cocaine exposure is associated with an attenuation of mPFC GABAergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD35 to PD65 is lacking following early adolescent cocaine treatment. Conclusion Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders. PMID:23558299

  12. Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

    PubMed

    Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

    2017-02-01

    Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

  13. Effects of developmental lead exposure on the hippocampal methylome: Influences of sex and timing and level of exposure.

    PubMed

    Singh, G; Singh, V; Wang, Zi-Xuan; Voisin, G; Lefebvre, F; Navenot, J-M; Evans, B; Verma, M; Anderson, D W; Schneider, J S

    2018-06-15

    Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigenetic changes, including alterations in DNA methylation, that can influence gene expression patterns and affect the function and development of the nervous system. The present promoter-based methylation microarray profiling study explored the extent to which developmental Pb exposure may modify the methylome of a brain region, hippocampus, known to be sensitive to the effects of Pb exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375 ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation), early postnatal exposures (birth through weaning), or long-term postnatal exposures (birth through postnatal day 55). Results showed a significant contribution of sex to the hippocampal methylome and effects of Pb exposure level, with non-linear dose response effects on methylation. Surprisingly, the developmental period of exposure contributed only a small amount of variance to the overall data and gene ontology (GO) analysis revealed the largest number of overrepresented GO terms in the groups with the lowest level of exposure. The highest number of significant differentially methylated regions was found in females exposed to Pb at the lowest exposure level. Our data reinforce the significant effect that low level Pb exposure may have on gene-specific DNA methylation patterns in brain and that this occurs in a sex-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. The Relationship between Prenatal and Postnatal Exposure to Polychlorinated Biphenyls (PCBs) and Cognitive, Neuropsychological, and Behavioral Deficits: A Critical Appraisal

    ERIC Educational Resources Information Center

    Cicchetti, Domenic V.; Kaufman, Alan S.; Sparrow, Sara S.

    2004-01-01

    Our purpose in this report is to evaluate scientifically that body of literature relating the effects of prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) upon neurobehavioral, health-related, and cognitive deficits in neonates, developing infants, children, and adults. The data derive from seven cohorts: six cohorts of mothers…

  15. In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.

    PubMed

    Aasa, Kristiina L; Maciver, Rebecca D; Ramchandani, Shyamlal; Adams, Michael A; Ozolinš, Terence R S

    2015-11-01

    Congenital heart defects (CHD) are the most common birth anomaly and while many resolve spontaneously by 1 year of age, the lifelong burden on survivors is poorly understood. Using a rat model of chemically induced CHD that resolve postnatally, we sought to characterize the postnatal changes in cardiac function, and to investigate whether resolved CHD affects the ability to adapt to the increased the cardiovascular (CV) burden of pregnancy. To generate rats with resolved CHD, pregnant rats were administered distilled water or dimethadione (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. To characterize structural and functional changes in the heart, treated and control offspring were scanned by echocardiography on postnatal day 4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring of hemodynamics. Females were mated and scanned by echocardiography on gd12 and gd18 during pregnancy. On gd18, maternal hearts were collected for structural and molecular assessment. Postnatal echocardiography revealed numerous structural and functional differences in treated offspring compared with control; however, these resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences between treated and control offspring with respect to mean arterial pressure, CV function, cardiac strain, and left ventricular gene expression. In utero exposure to DMO also affected the subsequent generation. Gd18 fetal and placental weights were increased in treated F2 offspring. This study demonstrates that in utero chemical exposure may permanently alter the capacity of the postnatal heart to adapt to pregnancy and this may have transgenerational effects. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. LONG TERM EFFECTS OF PRENATAL AND POSTNATAL AIRBORNE PAH EXPOSURE ON VENTILATORY LUNG FUNCTION OF NON-ASTHMATIC PREADOLESCENT CHILDREN. PROSPECTIVE BIRTH COHORT STUDY IN KRAKOW

    PubMed Central

    Jedrychowski, Wieslaw A.; Perera, Frederica P.; Maugeri, Umberto; Majewska, Renata; Mroz, Elzbieta; Flak, Elzbieta; Camman, David; Sowa, Agata; Jacek, Ryszard

    2014-01-01

    The main goal of the study was to test the hypothesis that prenatal and postnatal exposure to polycyclic aromatic hydrocarbons (PAH) is associated with depressed lung function in non-asthmatic children. The study sample comprises 195 non-asthmatic children of non-smoking mothers, among whom the prenatal PAH exposure was assessed by personal air monitoring in pregnancy. At the age of 3, residential air monitoring was carried out to evaluate the residential PAH exposure indoors and outdoors. At the age of 5 to 8, children were given allergic skin tests for indoor allergens; and between 5–9 years lung function testing (FVC, FEV05, FEV1 and FEF25–75) was performed. The effects of prenatal PAH exposure on lung function tests repeated over the follow-up were adjusted in the General Estimated Equation (GEE) model for the relevant covariates. No association between FVC with prenatal PAH exposure was found; however for the FEV1 deficit associated with higher prenatal PAH exposure (above 37ng/m3) amounted to 53 mL (p = 0.050) and the deficit of FEF25–75 reached 164 mL (p=0.013). The corresponding deficits related to postnatal residential indoor PAH level (above 42 ng/m3) were 59 mL of FEV1 (p=0.028) and 140 mL of FEF25–75 (p=0.031). At the higher residential outdoor PAH level (above 90 ng/m3) slightly greater deficit of FEV1 (71mL, p = 0.009) was observed. The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure. PMID:25300014

  17. Long term effects of prenatal and postnatal airborne PAH exposures on ventilatory lung function of non-asthmatic preadolescent children. Prospective birth cohort study in Krakow.

    PubMed

    Jedrychowski, Wieslaw A; Perera, Frederica P; Maugeri, Umberto; Majewska, Renata; Mroz, Elzbieta; Flak, Elzbieta; Camann, David; Sowa, Agata; Jacek, Ryszard

    2015-01-01

    The main goal of the study was to test the hypothesis that prenatal and postnatal exposures to polycyclic aromatic hydrocarbons (PAH) are associated with depressed lung function in non-asthmatic children. The study sample comprises 195 non-asthmatic children of non-smoking mothers, among whom the prenatal PAH exposure was assessed by personal air monitoring in pregnancy. At the age of 3, residential air monitoring was carried out to evaluate the residential PAH exposure indoors and outdoors. At the age of 5 to 8, children were given allergic skin tests for indoor allergens; and between 5 and 9 years lung function testing (FVC, FEV05, FEV1 and FEF25-75) was performed. The effects of prenatal PAH exposure on lung function tests repeated over the follow-up were adjusted in the General Estimated Equation (GEE) model for the relevant covariates. No association between FVC with prenatal PAH exposure was found; however for the FEV1 deficit associated with higher prenatal PAH exposure (above 37 ng/m(3)) amounted to 53 mL (p=0.050) and the deficit of FEF25-75 reached 164 mL (p=0.013). The corresponding deficits related to postnatal residential indoor PAH level (above 42 ng/m(3)) were 59 mL of FEV1 (p=0.028) and 140 mL of FEF25-75 (p=0.031). At the higher residential outdoor PAH level (above 90 ng/m(3)) slightly greater deficit of FEV1 (71 mL, p=0.009) was observed. The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Pre- and postnatal stress and asthma in children: Temporal- and sex-specific associations

    PubMed Central

    Lee, Alison; Chiu, Yueh-Hsiu Mathilda; Rosa, Maria José; Jara, Calvin; Wright, Robert O.; Coull, Brent A.; Wright, Rosalind J.

    2016-01-01

    BACKGROUND Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES We examined associations between pre- and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. METHODS Maternal negative life events (NLEs) were ascertained prenatally and postpartum. NLEs scores were categorized as 0, 1-2, 3-4, or ≥5 to assess exposure-response relationships. We examined effects of pre- and postnatal stress on children's asthma by age 6 years modeling each as independent predictors; mutually adjusting for prenatal and postnatal stress; and finally considering interactions between pre- and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS When considering stress in each period independently, among boys a dose-response relationship was evident for each level increase on the ordinal scale prenatally (OR=1.38, 95% CI 1.06, 1.79; p-for-trend=0.03) and postnatally (OR=1.53, 95% CI 1.16, 2.01; p-for-trend=0.001); among girls only the postnatal trend was significant (OR=1.60, 95% CI 1.14, 2.22; p-for-trend=0.005). Higher stress in both the pre- and postnatal periods was associated with increased odds of being diagnosed with asthma in girls [OR=1.37, 95% CI 0.98, 1.91 (pinteraction=0.07)] but not boys [OR=1.08, 95% CI 0.82, 1.42 (pinteraction=0.61)]. CONCLUSIONS While boys were more vulnerable to stress during the prenatal period, girls were more impacted by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early life stress may provide unique insight into asthma etiology and natural history. PMID:26953156

  19. ATRAZINE-INDUCED REPRODUCTIVE TRACT ALTERATIONS AFTER TRANSPLACENTAL AND LACTATIONAL EXPOSURE IN LONG-EVANS RAT PUPS

    EPA Science Inventory

    Studies have shown that early postnatal exposure to the common herbicide atrazine (ATR) will delay preputial separation (PPS) in Wistar rats and increase incidence of prostate inflammation in adults. To evaluate ATR exposure parameters required for pubertal delays (PPS), we used...

  20. Brief postnatal exposure to phenobarbital impairs passive-avoidance learning and sensorimotor gating in rats

    PubMed Central

    Gutherz, Samuel B.; Kulick, Catherine V.; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A.

    2014-01-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference to cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition as compared to vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention as compared to matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. PMID:25112558

  1. Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.

    PubMed

    Gutherz, Samuel B; Kulick, Catherine V; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A

    2014-08-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Exploratory behavior in rats postnatally exposed to cocaine and housed in an enriched environment.

    PubMed

    Magalhães, Ana; Melo, Pedro; Alves, Cecília Juliana; Tavares, Maria Amélia; de Sousa, Liliana; Summavielle, Teresa

    2008-10-01

    Exposure to cocaine in early periods of postnatal life is usually associated with changes in development of neurotransmitter systems and structure of the central nervous system. Such changes are most likely correlated with behavioral alterations. Environmental enrichment conditions (EC) in early stages is a factor that affects structural and behavioral development. The purpose of this study is to examine the effects of EC on rats postnatally exposed to cocaine on exploratory behavior. Wistar rats were assigned to four groups-Group 1: pups exposed to cocaine hydrochloride (15 mg/kg body weight/day) s.c., in two daily doses, from postnatal day (PND) 1 to 28 and reared in EC; Group 2: pups exposed to cocaine as previously described and reared in a standard environmental conditions (SC); Group 3: pups saline-injected and reared in EC; and Group 4: pups saline-injected and reared in SC. On PND 21, 24, and 28, groups of four rats (to reduce anxiety) were placed for 10 minutes into an arena with several objects. The following exploratory behavioral categories were examined: object interaction, exploration, manipulation, approximation, and total time of object contact. Animals from Group 2 showed decreased object interaction and total contact on PND 21. Control offspring reared in EE showed decreases in exploratory behavior at all ages analyzed compared with the control SE group, while cocaine-exposed animals reared in EC showed decreased object interaction, object approximation, and total exploratory behavior. The results in this group suggest that EC improved information acquisition and memory processes in animals postnatally exposed to cocaine.

  3. The perception of pre- and post-natal marijuana exposure on health outcomes: A content analysis of twitter messages.

    PubMed

    Dakkak, H; Brown, R; Twynstra, J; Charbonneau, K; Seabrook, J A

    2018-05-23

    The prevalence of marijuana use during pregnancy ranges from 3- 30% , and most of this is for recreational purposes. Marijuana exposure during pregnancy has been linked with low birth weight babies and other adverse child health outcomes. Twitter is a popular news and social networking outlet, and is frequently used to access information about population health and behavior. The primary objective of this study was to investigate the types of messages disseminated on Twitter about marijuana use and infant and maternal health. The secondary objective was to describe the reported health outcomes associated with prenatal and postnatal marijuana use. Tweets were collected from the inception of Twitter (2006) until April 2017. If tweets included links, these links were examined to investigate the source of the message and to clarify the user's intent. In total, 550 tweets were captured, with most tweets (77.6%) having a neutral tweet tone, suggesting uncertainty about the health effects associated with pre- and post-natal marijuana exposure. The sources attached to the original tweets, however, were more likely to report on negative health outcomes. The most common health outcomes associated with prenatal marijuana exposure were: poor brain development (27.3%), inadequate development of the nervous system (23.6%), low birth weight (23.3%), poor behavioral outcomes (21.0%), and infant memory issues (19.3%). The inverse association between marijuana use and the quality and quantity of milk produced by the mother was the most commonly reported tweet for the lactation period.

  4. Glial glycine transporter 1 function is essential for early postnatal survival but dispensable in adult mice.

    PubMed

    Eulenburg, Volker; Retiounskaia, Marina; Papadopoulos, Theofilos; Gomeza, Jesús; Betz, Heinrich

    2010-07-01

    The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine-mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N-methyl-D-asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory synapses, we inactivated the GlyT1 gene cell type-specifically using mice carrying floxed GlyT1 alleles GlyT1((+)/+)). GlyT1((+)/(+)) mice expressing Cre recombinase in glial cells developed severe neuromotor deficits during the first postnatal week, which mimicked the phenotype of conventional GlyT1 knock-out mice and are consistent with glycinergic over-inhibition. In contrast, Cre-mediated inactivation of the GlyT1 gene in neuronal cells did not result in detectable motor impairment. Notably, some animals deficient for glial GlyT1 survived the first postnatal week and did not develop neuromotor deficits throughout adulthood, although GlyT1 expression was efficiently reduced. Thus, glial GlyT1 is critical for the regulation of glycine levels at inhibitory synapses only during early postnatal life. Copyright 2010 Wiley-Liss, Inc.

  5. ATRAZINE-INDUCED REPRODUCTIVE TRACT ALTERATIONS AFTER TRANSPLACENTAL AND LACTATIONAL EXPOSURE IN MALE LONG-EVANS RATS.

    EPA Science Inventory

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR wou...

  6. The SIX1 Oncoprotein Mediates Aberrant Endometrial Basal Cell Development Following Neonatal Exposure to Diethylstilbestrol

    EPA Science Inventory

    Early-life exposures can disrupt cellular differentiation and contribute to increased cancer risk later in life. In a model of developmental estrogen exposure, female mice exposed on postnatal day (PND) 1-5 to diethylstilbestrol (DES) develop a high incidence of endometrial adeno...

  7. The effect of prenatal TVOC exposure on birth and infantile weight: the Mothers and Children's Environmental Health study.

    PubMed

    Chang, Moonhee; Park, Hyesook; Ha, Mina; Hong, Yun-Chul; Lim, Youn-Hee; Kim, Yangho; Kim, Young Ju; Lee, Dongheon; Ha, Eun-Hee

    2017-09-01

    BACKGROUNDVolatile organic compounds (VOCs) might restrict prenatal and postnatal growth. However, the effect of the exposure of prenatal VOCs on postnatal growth has not been studied sufficiently. Thus, we investigated the relationship between the exposure of total volatile organic compounds (TVOCs) during pregnancy and its effects on postnatal growth.METHODSA total of 383 pregnant participants were enrolled from 2006 to 2008. We investigated maternal characteristics using a questionnaire. Personal air samples of TVOCs were obtained in mid or late pregnancy. After these mothers had given birth, 360 singleton newborns were selected and postnatal follow-up data were collected at 6, 12, 24, and 36 months, as well as anthropometric factors including body weight. Multiple general linear and mixed models were applied for statistical analyses.RESULTSThe mean concentration of prenatal exposure to TVOCs was 284.2 μg/m 3 and that of formaldehyde was 81.6 μg/m 3 . The birth weight of newborns decreased significantly with prenatal TVOC exposure (β=-45.89, P=0.04). The adjusted mean body weight was 300 g lower in the high-TVOC group (⩾75th) compared with that in the low-exposure group (<75th).CONCLUSIONThese results indicate that elevated exposure to TVOCs during the prenatal period may adversely influence early postnatal growth.

  8. Telomere length dynamics differ in foetal and early post-natal human leukocytes in a longitudinal study.

    PubMed

    Holmes, Denise K; Bellantuono, Ilaria; Walkinshaw, Steve A; Alfirevic, Zarko; Johnston, Tracey A; Subhedar, Nimish V; Chittick, Rachel; Swindell, Richard; Wynn, Robert F

    2009-06-01

    Haemopoietic stem cells (HSC) undergo a process of self renewal to constantly maintain blood cell turnover. However, it has become apparent that adult HSC lose their self-renewal ability with age. Telomere shortening in peripheral blood leukocytes has been seen to occur with age and it has been associated with loss of HSC proliferative capacity and cellular ageing. In contrast foetal HSC are known to have greater proliferative capacity than post-natal stem cells. However it is unknown whether they undergo a similar process of telomere shortening. In this study we show a more accentuated rate of telomere loss in leukocytes from pre term infants compared to human foetuses of comparable age followed longitudinally for 8-12 weeks in a longitudinal study. Our results point to a difference in HSC behaviour between foetal and early postnatal life which is independent of age but may be influenced by events at birth itself.

  9. The microbiome in early life: implications for health outcomes.

    PubMed

    Tamburini, Sabrina; Shen, Nan; Wu, Han Chih; Clemente, Jose C

    2016-07-07

    Recent studies have characterized how host genetics, prenatal environment and delivery mode can shape the newborn microbiome at birth. Following this, postnatal factors, such as antibiotic treatment, diet or environmental exposure, further modulate the development of the infant's microbiome and immune system, and exposure to a variety of microbial organisms during early life has long been hypothesized to exert a protective effect in the newborn. Furthermore, epidemiological studies have shown that factors that alter bacterial communities in infants during childhood increase the risk for several diseases, highlighting the importance of understanding early-life microbiome composition. In this review, we describe how prenatal and postnatal factors shape the development of both the microbiome and the immune system. We also discuss the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations.

  10. Sex-based differences in gene expression in hippocampus following postnatal lead exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schneider, J.S., E-mail: jay.schneider@jefferson.edu; Anderson, D.W.; Sonnenahalli, H.

    The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 {+-} 2.1 {mu}g/dl and 27.1 {+-} 1.7 {mu}g/dl for females and males, respectively. The expression of 175more » unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: > Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. > At least one set of genes was affected in opposite directions in males and females. > Differentially expressed genes were associated with diverse biological pathways.« less

  11. Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

    PubMed Central

    Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

    2013-01-01

    Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

  12. [Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation].

    PubMed

    Cai, Yue-Ju; Song, Yan-Yan; Huang, Zhi-Jian; Li, Jian; Qi, Jun-Ye; Xiao, Xu-Wen; Wang, Lan-Xiu

    2015-09-01

    To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well. Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

  13. Early valproic acid exposure alters functional organization in the primary visual cortex

    PubMed Central

    Pohl-Guimaraes, Fernanda; Krahe, Thomas E.; Medina, Alexandre E.

    2018-01-01

    Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200 mg/kg), Lev (100 mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42–P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val-but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. PMID:21215743

  14. Early valproic acid exposure alters functional organization in the primary visual cortex.

    PubMed

    Pohl-Guimaraes, Fernanda; Krahe, Thomas E; Medina, Alexandre E

    2011-03-01

    Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200mg/kg), Lev (100mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42-P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val- but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. IDENTIFICATION OF NEURAL BIOMARKERS OF ALTERED SEXUAL DIFFERENTIATION FOLLOWING GESTATIONAL EXPOSURE***

    EPA Science Inventory

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  16. Identification of neural biomarkers of altered sexual differentiation following gestational exposure

    EPA Science Inventory

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) during...

  17. Identification of neural biomarkers of altered sexual differentiation following gestational exposure###

    EPA Science Inventory

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  18. Active retinitis in an infant with postnatally acquired cytomegalovirus infection.

    PubMed

    Piersigilli, F; Catena, G; De Gasperis, M R; Lozzi, S; Auriti, C

    2012-07-01

    Congenital cytomegalovirus (CMV) is frequently associated with active retinitis. In contrast, in the immunocompetent neonate with postnatally acquired CMV infection retinitis is rarely present and usually does not progress. We describe the case of an infant with postnatal CMV infection and active retinitis diagnosed at 20 days of life. Owing to the rapid progression of the retinitis, therapy with intravenous ganciclovir was performed, with prompt regression of the retinitis. Therapy was then continued with oral valganciclovir for one further week. Although very unusual, CMV retinitis has to be taken into consideration in neonates with early postnatally acquired CMV infection, as an early diagnosis and treatment may be crucial to avoid visual impairment.

  19. Pre- and Early-Postnatal Nutrition Modify Gene and Protein Expressions of Muscle Energy Metabolism Markers and Phospholipid Fatty Acid Composition in a Muscle Type Specific Manner in Sheep

    PubMed Central

    Hou, Lei; Kongsted, Anna H.; Ghoreishi, Seyed M.; Takhtsabzy, Tasnim K.; Friedrichsen, Martin; Hellgren, Lars I.; Kadarmideen, Haja N.; Vaag, Allan; Nielsen, Mette O.

    2013-01-01

    We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole

  20. The investigation of the prenatal and postnatal alcohol exposure-induced neurodegeneration in rat brain: protection by betaine and/or omega-3.

    PubMed

    Kusat Ol, Kevser; Kanbak, Güngör; Oğlakcı Ilhan, Ayşegül; Burukoglu, Dilek; Yücel, Ferruh

    2016-03-01

    We aim to study the effect of neurodegeneration on the brain of rat pups caused by prenatal and postnatal ethanol exposure with modified liquid diet to elucidate protective effects of betaine and omega-3 supplementation. When ethanol is consumed during prenatal and postnatal periods, it may result in fetal alcohol syndrome (FAS) in the offspring. Rats were divided into control, ethanol, ethanol + betaine, ethanol + omega-3, ethanol + omega-3 + betaine groups. The effect of betaine and omega-3 in response to ethanol-induced changes on the brain, by biochemical analyses cytochrome c, caspase-3, calpain, cathepsin B and L, DNA fragmentation, histological and morfometric methods were evaluated. Caspase-3, calpain, cathepsin B, and cytochrome c levels in ethanol group were significantly higher than control. Caspase-3, calpain levels were decreased in ethanol + betaine, ethanol + omega-3, and ethanol + omega-3 + betaine groups compared to ethanol group. Cathepsin B in ethanol + omega-3 + betaine group was decreased compared to ethanol, ethanol + betaine groups. Cathepsin L and DNA fragmentation were found not statistically significant. We found similar results in histological and morfometric parameters. We found that pre- and postnatal ethanol exposure is capable of triggering necrotic cell death in rat brains, omega-3, and betaine reduce neurodegeneration. Omega-3 and betaine may prove beneficial for neurodegeneration, particularly in preventing FAS.

  1. The effects of postnatal phthalate exposure on the development of auditory temporal processing in rats.

    PubMed

    Kim, Bong Jik; Kim, Jungyoon; Keoboutdy, Vanhnansy; Kwon, Ho-Jang; Oh, Seung-Ha; Jung, Jae Yun; Park, Il Yong; Paik, Ki Chung

    2017-06-01

    The central auditory pathway is known to continue its development during the postnatal critical periods and is shaped by experience and sensory inputs. Phthalate, a known neurotoxic material, has been reported to be associated with attention deficits in children, impacting many infant neurobehaviors. The objective of this study was to investigate the potential effects of neonatal phthalate exposure on the development of auditory temporal processing. Neonatal Sprague-Dawley rats were randomly assigned into two groups: The phthalate group (n = 6), and the control group (n = 6). Phthalate was given once per day from postnatal day 8 (P8) to P28. Upon completion, at P28, the Auditory Brainstem Response (ABR) and Gap Prepulse Inhibition of Acoustic Startle response (GPIAS) at each gap duration (2, 5, 10, 20, 50 and 80 ms) were measured, and gap detection threshold (GDT) was calculated. These outcomes were compared between the two groups. Hearing thresholds by ABR showed no significant differences at all frequencies between the two groups. Regarding GPIAS, no significant difference was observed, except at a gap duration of 20 ms (p = 0.037). The mean GDT of the phthalate group (44.0 ms) was higher than that of the control group (20.0 ms), but without statistical significance (p = 0.065). Moreover, the phthalate group tended to demonstrate more of a scattered distribution in the GDT group than the in the control group. Neonatal phthalate exposure may disrupt the development of auditory temporal processing in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Early Life Exposures and Cancer

    Cancer.gov

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  3. Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

    PubMed

    Perucho, Juan; Gómez, Ana; Muñoz, María Paz; de Yébenes, Justo García; Mena, María Ángeles; Casarejos, María José

    2016-07-01

    The pathological hallmark of Huntington disease (HD) is the intracellular aggregation of mutant huntingtin (mHTT) in striatal neurons and glia associated with the selective loss of striatal medium-sized spiny neurons. Up to the present, the role of glia in HD is poorly understood and has been classically considered secondary to neuronal disorder. Trehalose is a disaccharide known to possess many pharmacological properties, acting as an antioxidant, a chemical chaperone, and an inducer of autophagy. In this study, we analyzed at an early postnatal development stage the abnormalities observed in striatal glial cell cultures of postnatal R6/1 mice (HD glia), under baseline and stressing conditions and the protective effects of trehalose. Our data demonstrate that glial HD alterations already occur at early stages of postnatal development. After 20 postnatal days in vitro, striatal HD glia cultures showed more reactive astrocytes with increased expression of glial fibrillary acidic protein (GFAP) but with less replication capacity, less A2B5(+) glial progenitors and more microglia than wild-type (WT) cultures. HD glia had lower levels of intracellular glutathione (GSH) and was more susceptible to H2O2 and epoxomicin insults. The amount of expressed GDNF and secreted mature-BDNF by HD astrocytes were much lower than by WT astrocytes. In addition, HD glial cultures showed a deregulation of the major proteolytic systems, the ubiquitin-proteasomal system (UPS), and the autophagic pathway. This produces a defective protein quality control, indicated by the elevated levels of ubiquitination and p62 protein. Interestingly, we show that trehalose, through its capacity to induce autophagy, inhibited p62/SQSTM1 accumulation and facilitated the degradation of cytoplasmic aggregates from mHTT and α-synuclein proteins. Trehalose also reduced microglia activation and reversed the disrupted cytoskeleton of astrocytes accompanied with an increase in the replication capacity. In

  4. Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood

    PubMed Central

    Clinton, Sarah M.; Glover, Matthew E.; Maltare, Astha; Laszczyk, Ann M.; Mehi, Stephen J.; Simmons, Rebecca K.; King, Gwendalyn D.

    2013-01-01

    Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development. PMID:23838326

  5. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

    PubMed

    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  6. The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats.

    PubMed

    Nagapan, Gowri; Meng Goh, Yong; Shameha Abdul Razak, Intan; Nesaretnam, Kalanithi; Ebrahimi, Mahdi

    2013-07-31

    Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus

  7. Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

    PubMed

    Lee, Alison; Mathilda Chiu, Yueh-Hsiu; Rosa, Maria José; Jara, Calvin; Wright, Robert O; Coull, Brent A; Wright, Rosalind J

    2016-09-01

    Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Postnatal BMI changes in children with different birthweights: A trial study for detecting early predictive factors for pediatric obesity

    PubMed Central

    Nakagawa, Yuichi; Nakanishi, Toshiki; Satake, Eiichiro; Matsushita, Rie; Saegusa, Hirokazu; Kubota, Akira; Natsume, Hiromune; Shibata, Yukinobu; Fujisawa, Yasuko

    2018-01-01

    Abstract. The purpose of this study was to clarify the degree of early postnatal growth by birthweight and detect early predictive factors for pediatric obesity. Body mass index (BMI) and degree of obesity were examined in children in the fourth year of elementary school and second year of junior high school. Their BMI at birth and three years of age were also examined. Based on birthweight, participants were divided into three groups: low (< 2500 g), middle (2500–3500 g), and high (> 3500 g). Furthermore, according to the degree of obesity, they were divided into two groups: obese (20% ≤) and non-obese (20% >). The change of BMI from birth to three years of age (ΔBMI) showed a strong inverse relationship with birthweight and was significantly different among the three birthweight groups (low > middle > high). The ΔBMI and BMI at three years of age were higher in obese than in non-obese children and showed significant positive correlations with the degree of obesity. Early postnatal growth might be determined by birthweight and was higher in obese than in non-obese children. The ΔBMI from birth to three years of age and BMI at age of three years could be predictive factors for pediatric obesity. PMID:29403153

  9. A developmental perspective on early-life exposure to neurotoxicants.

    PubMed

    Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

    2016-09-01

    Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Early-life exposure to substance abuse and risk of type 2 diabetes in adulthood.

    PubMed

    Vaiserman, A M

    2015-08-01

    Type 2 diabetes (T2D) is a chronic non-communicable disease that is driven by insulin resistance as a result of increasing obesity and decreasing activity levels that occur with increasing age. This disease generally develops after the age of 40, but it is now increasingly diagnosed in children and young adults. Increasing evidence, however, suggests that T2D can originate during early development. It has been repeatedly found that malnutrition during the gestational period can result in intrauterine growth restriction and low birth weight, which in combination with postnatal catch-up growth may subsequently lead to the development of T2D. There is ample evidence that T2D may also be programmed by maternal substance abuse (the harmful use of psychoactive substances such as illicit drugs or alcohol) during pregnancy and/or lactation. The research activity in this field is currently mainly focused on the childhood health problems following prenatal exposures to substance abuse. The delayed programming effects on adult-onset disorders, including metabolic syndrome and T2D, however, have been reported only rarely. This review provides animal and human evidence that early-life exposure to substance abuse, including alcohol, nicotine, and cocaine, may program not only childhood health outcomes but also life-long metabolic health status, including risk of T2D and related conditions.

  11. Risk factors for antenatal depression, postnatal depression and parenting stress

    PubMed Central

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-01-01

    Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program [1]. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Results Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors

  12. Risk factors for antenatal depression, postnatal depression and parenting stress.

    PubMed

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-04-16

    Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26-32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10-12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Risk factor profiles for

  13. Prenatal and early-life polychlorinated biphenyl (PCB) levels and behavior in Inuit preschoolers.

    PubMed

    Verner, Marc-André; Plusquellec, Pierrich; Desjardins, Justine Laura; Cartier, Chloé; Haddad, Sami; Ayotte, Pierre; Dewailly, Éric; Muckle, Gina

    2015-05-01

    Whereas it is well established that prenatal exposure to polychlorinated biphenyls (PCBs) can disrupt children's behavior, early postnatal exposure has received relatively little attention in environmental epidemiology. To evaluate prenatal and postnatal exposures to PCB-153, a proxy of total PCB exposure, and their relation to inattention and activity in 5-year-old Inuits from the Cord Blood Monitoring Program. Prenatal exposure to PCBs was informed by cord plasma PCB-153 levels. We used a validated pharmacokinetic model to estimate monthly infants' levels across the first year of life. Inattention and activity were assessed by coding of video recordings of children undergoing fine motor testing. We used multivariable linear regression to evaluate the association between prenatal and postnatal PCB-153 levels and inattention (n=97) and activity (n=98) at 5years of age. Cord plasma PCB-153 was not associated with inattention and activity. Each interquartile range (IQR) increase in estimated infant PCB-153 levels at 2months was associated with a 1.02% increase in the duration of inattention (95% CI: 0.04, 2.00). Statistical adjustment for the duration of breastfeeding slightly increased regression coefficients for postnatal level estimates, some of which became statistically significant for inattention (months: 2-4) and activity (months: 2-5). Our study adds to the growing evidence of postnatal windows of development during which children are more susceptible to neurotoxicants like PCBs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

    PubMed

    Ikeda, Naho; Shoji, Hiromichi; Suganuma, Hiroki; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki

    2016-05-01

    Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period. © 2015 Japan Pediatric Society.

  15. Bisphenol A Exposure Disrupts Genomic Imprinting in the Mouse

    PubMed Central

    Susiarjo, Martha; Sasson, Isaac; Mesaros, Clementina; Bartolomei, Marisa S.

    2013-01-01

    Exposure to endocrine disruptors is associated with developmental defects. One compound of concern, to which humans are widely exposed, is bisphenol A (BPA). In model organisms, BPA exposure is linked to metabolic disorders, infertility, cancer, and behavior anomalies. Recently, BPA exposure has been linked to DNA methylation changes, indicating that epigenetic mechanisms may be relevant. We investigated effects of exposure on genomic imprinting in the mouse as imprinted genes are regulated by differential DNA methylation and aberrant imprinting disrupts fetal, placental, and postnatal development. Through allele-specific and quantitative real-time PCR analysis, we demonstrated that maternal BPA exposure during late stages of oocyte development and early stages of embryonic development significantly disrupted imprinted gene expression in embryonic day (E) 9.5 and 12.5 embryos and placentas. The affected genes included Snrpn, Ube3a, Igf2, Kcnq1ot1, Cdkn1c, and Ascl2; mutations and aberrant regulation of these genes are associated with imprinting disorders in humans. Furthermore, the majority of affected genes were expressed abnormally in the placenta. DNA methylation studies showed that BPA exposure significantly altered the methylation levels of differentially methylated regions (DMRs) including the Snrpn imprinting control region (ICR) and Igf2 DMR1. Moreover, exposure significantly reduced genome-wide methylation levels in the placenta, but not the embryo. Histological and immunohistochemical examinations revealed that these epigenetic defects were associated with abnormal placental development. In contrast to this early exposure paradigm, exposure outside of the epigenetic reprogramming window did not cause significant imprinting perturbations. Our data suggest that early exposure to common environmental compounds has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta. PMID

  16. Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence.

    PubMed

    Vaiserman, Alexander M

    2017-03-05

    Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed.

  17. Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence

    PubMed Central

    Vaiserman, Alexander M.

    2017-01-01

    Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies (‘natural experiments’). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed. PMID:28273874

  18. Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development.

    PubMed

    Kozul-Horvath, Courtney D; Zandbergen, Fokko; Jackson, Brian P; Enelow, Richard I; Hamilton, Joshua W

    2012-01-01

    Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations.

  19. Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

    PubMed

    Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

    2017-09-11

    Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

  20. Early-Life Phthalate Exposure and Adiposity at 8 Years of Age

    PubMed Central

    Papandonatos, George D.; Calafat, Antonia M.; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P.; Yolton, Kimberly; Braun, Joseph M.

    2017-01-01

    Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 PMID:28935615

  1. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodentmore » model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.« less

  2. Domain specific effects of postnatal toenail methylmercury exposure on child behaviour.

    PubMed

    Karatela, Shamshad; Paterson, Janis; Ward, Neil I

    2017-05-01

    Very little is known about the relationship between postnatal methylmercury concentrations (via toenails as bioindicator) and behavioural characteristics of Pacific Island children living in New Zealand. The aim of this study was to explore the association between total mercury exposure and different domains of behavioural problems in Pacific children. A sample of nine-year-old Pacific Island children resident in Auckland, New Zealand participated in this study. Total mercury was determined in biological samples (toenail clippings) on behavioural problems as identified by mothers (using the child behaviour checklist). Specific behavioural domains, particularly aggression, rule breaking, attention and social problems were studied in relation to mercury exposure using toenails. The determination of mercury concentration in toenail clippings, after acid digestion was carried out using inductively coupled plasma mass spectrometry. The observational study was conducted between July 2010 and July 2011 in which 278 eligible nine-year-old Pacific Island children were enrolled (Girls n=58%; boys n=42%). showed that 21% of the children had total toenail mercury concentrations (1.5μg/g to 6μg/g) higher than the United State Environmental Protection Agency recommended levels (RfD; 1μg/g Hg) for optimal health in children. Aggressive behaviour was associated with total toenail mercury exposure after adjusting for gender, ethnicity and income levels (OR: 2.15 95% CI 1.45, 3.18 p-value <0.05; OR 1.38 95% CI 0.83, 1.2 p value <0.05, respectively). Overall, this research contributes to the understanding of total toenail mercury concentrations for Pacific people in New Zealand using toenail clippings as biomarkers in terms of associations with child behavioural problems. Mercury in toenails demonstrated a moderate association with a specific behavioural domain - aggressive behaviour. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Infant frontal EEG asymmetry in relation with postnatal maternal depression and parenting behavior.

    PubMed

    Wen, D J; Soe, N N; Sim, L W; Sanmugam, S; Kwek, K; Chong, Y-S; Gluckman, P D; Meaney, M J; Rifkin-Graboi, A; Qiu, A

    2017-03-14

    Right frontal electroencephalogram (EEG) asymmetry associates with negative affect and depressed mood, which, among children, are predicted by maternal depression and poor parenting. This study examined associations of maternal depression and maternal sensitivity with infant frontal EEG asymmetry based on 111 mother-6-month-infant dyads. There were no significant effects of postnatal maternal depression or maternal sensitivity, or their interaction, on infant EEG frontal asymmetry. However, in a subsample for which the infant spent at least 50% of his/her day time hours with his/her mother, both lower maternal sensitivity and higher maternal depression predicted greater relative right frontal EEG asymmetry. Our study further showed that greater relative right frontal EEG asymmetry of 6-month-old infants predicted their greater negative emotionality at 12 months of age. Our study suggested that among infants with sufficient postnatal maternal exposure, both maternal sensitivity and mental health are important influences on early brain development.

  4. Early postnatal weight gain as a predictor for the development of retinopathy of prematurity.

    PubMed

    Biniwale, Manoj; Weiner, Angela; Sardesai, Smeeta; Cayabyab, Rowena; Barton, Lorayne; Ramanathan, Rangasamy

    2017-10-01

    The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.

  5. Ozone and allergen exposure during postnatal development alters the frequency and airway distribution of CD25+ cells in infant rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, Lisa A.; California National Primate Research Center, University of California, Davis, CA 95616; Gerriets, Joan E.

    2009-04-01

    The epidemiologic link between air pollutant exposure and asthma has been supported by experimental findings, but the mechanisms are not understood. In this study, we evaluated the impact of combined ozone and house dust mite (HDM) exposure on the immunophenotype of peripheral blood and airway lymphocytes from rhesus macaque monkeys during the postnatal period of development. Starting at 30 days of age, monkeys were exposed to 11 cycles of filtered air, ozone, HDM aerosol, or ozone + HDM aerosol. Each cycle consisted of ozone delivered at 0.5 ppm for 5 days (8 h/day), followed by 9 days of filtered air;more » animals received HDM aerosol during the last 3 days of each ozone exposure period. Between 2-3 months of age, animals co-exposed to ozone + HDM exhibited a decline in total circulating leukocyte numbers and increased total circulating lymphocyte frequency. At 3 months of age, blood CD4+/CD25+ lymphocytes were increased with ozone + HDM. At 6 months of age, CD4+/CD25+ and CD8+/CD25+ lymphocyte populations increased in both blood and lavage of ozone + HDM animals. Overall volume of CD25+ cells within airway mucosa increased with HDM exposure. Ozone did not have an additive effect on volume of mucosal CD25+ cells in HDM-exposed animals, but did alter the anatomical distribution of this cell type throughout the proximal and distal airways. We conclude that a window of postnatal development is sensitive to air pollutant and allergen exposure, resulting in immunomodulation of peripheral blood and airway lymphocyte frequency and trafficking.« less

  6. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    PubMed Central

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

  7. Maternal exposure to fine particulate air pollution induces epithelial-to-mesenchymal transition resulting in postnatal pulmonary dysfunction mediated by transforming growth factor-β/Smad3 signaling.

    PubMed

    Tang, Wenting; Du, Lili; Sun, Wen; Yu, Zhiqiang; He, Fang; Chen, Jingsi; Li, Xiaomei; Li, Xiuying; Yu, Lin; Chen, Dunjin

    2017-02-05

    Fine particles from air pollution, also called particulate matter, less than 2.5 micrometers in diameter (PM2.5), are a threat to child health. Epidemiological investigations have related maternal exposure to PM2.5 to postnatal respiratory symptoms, such as frequent wheezing, chronic cough, and lung function decrements. However, only few experimental animal studies have been performed to study the effects of PM2.5.The aim of this study was to investigate the effects of maternal exposure to PM2.5 on postnatal pulmonary dysfunction in a rat model and to examine the mechanism of PM2.5-induced morphological pulmonary changes.Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5mg/kg) once every three days from day 0 to 18 of pregnancy. After delivery, pups were sacrificed on postnatal day (PND)1 and 28. The effects of transforming growth factor-beta (TGF-β) on epithelial-mesenchymal transition (EMT) were determined by immunohistochemistry, Western blotting, and quantitative RT-PCR. The offspring underwent pulmonary function measurements on PND28, lung tissues were histopathologically examined, and markers of oxidative stress were measured. Maternally PM2.5-exposed offspring pups displayed significant decreases in lung volume parameters, compliance, and airflow during expiration on PND28. The PM2.5-exposed group showed interstitial proliferation in lung histology, significant oxidative stress in lungs, and up-regulation of TGF-β-induced EMT via increased vimentin and α-smooth muscle actin and decreased E-cadherin levels on PND1 and PND28.These results suggest that EMT up-regulation mediated by the TGF-β/Smad3 pathway plays a role in postnatal pulmonary dysfunction associated with maternal exposure to PM2.5. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Early intervention to protect the mother-infant relationship following postnatal depression: study protocol for a randomised controlled trial.

    PubMed

    Milgrom, Jeannette; Holt, Charlene

    2014-10-03

    postnatal depression group treatment programme. Primary outcome measures are the Parenting Stress Index (self-report measure) and the Parent-child Early Relational Assessment (observational measure coded by a blinded observer). Measurements are taken at baseline, after the postnatal depression programme, post-HUGS/Playtime, and at 6 months post-HUGS/Playtime. This research addresses the need for specific treatment for mother-infant interactional difficulties following postnatal depression. There is a need to investigate interventions in randomised trials to prevent detrimental effects on child development and make available evidence-based treatments. Australia and New Zealand Clinical Trials Register: ACTRN12612001110875. Date Registered: 17 October 2012.

  9. Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

    PubMed

    Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

    2008-12-01

    Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

  10. The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats

    PubMed Central

    2013-01-01

    Background Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze.Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base

  11. Postnatal TLR2 activation impairs learning and memory in adulthood.

    PubMed

    Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

    2015-08-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Intestinal absorption and renal reabsorption of calcium throughout postnatal development

    PubMed Central

    Beggs, Megan R

    2017-01-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  13. COGNITIVE FUNCTION OF 6-YEAR OLD CHILDREN EXPOSED TO MOLD-CONTAMINATED HOMES IN EARLY POSTNATAL PERIOD. PROSPECTIVE BIRTH COHORT STUDY IN POLAND

    PubMed Central

    Jedrychowski, Wieslaw; Maugeri, Umberto; Stigter, Laura; Jankowski, Jeffrey; Butscher, Maria; Mroz, Elzbieta; Flak, Elzbieta; Skarupa, Anita; Sowa, Agata

    2013-01-01

    In the last decade, the neurologic effects of various air pollutants have been the focus of increasing attention. The main purpose of this study was to assess the potential impact of early childhood exposure to indoor molds on the subsequent cognitive function of 6-year old children. The results of this study are based on the six-year follow-up of 277 babies born at term to mothers participating in a prospective cohort study in Krakow, Poland. The study participants are all non-smoking pregnant women who were free of chronic diseases such as diabetes and hypertension. The presence of visible mold patches on indoor walls was monitored at regular time intervals over gestation and after birth up to the age of five. The Wechsler Intelligence Scale for Children (WISC-R) was administered to children at age 6. The exposure effect of living in mold-contaminated homes on the IQ scores of children was adjusted for major confounders, known to be important for the cognitive development of children such as maternal education, the child’s gender, breastfeeding practices in infancy, the presence of older siblings and the prenatal exposure to lead and environmental tobacco smoke (ETS). The adjusted IQ deficit attributed to longer exposures to indoor molds (> 2 years) was significantly lower on the IQ scale (beta coeff. = −9.16, 95%CI: −15.21, −3.10) and tripled the risk of low IQ scoring (OR= 3.53; 95%CI: 1.11 – 11.27) compared with references. While maternal education (beta coeff. = 0.61, 95%CI: 0.05, 1.17) and breastfeeding (beta coeff. = 4.0; 95%CI: 0.84, 7.17) showed a significant positive impact on cognitive function, prenatal ETS exposure (beta coeff. = −0.41; 95%CI: −0.79, −0.03) and the presence of older siblings (beta coefficient= −3.43; 95%CI: −5.67, −1.20) were associated with poorer cognitive function in children. In conclusion, the results of this study draw attention to the harmful effect of early postnatal exposure to indoor molds on children

  14. Associations of Baroreflex Sensitivity, Heart Rate Variability, and Initial Orthostatic Hypotension with Prenatal and Recent Postnatal Methylmercury Exposure in the Seychelles Child Development Study at Age 19 Years

    PubMed Central

    Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W.; Davidson, Philip W.; Myers, Gary J.; Bovet, Pascal

    2015-01-01

    Background: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Methods: Subjects in theSeychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects’ hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Results: Prenatal MeHg exposures were similar in boys and girls (6.7 ± 4.3, 6.7 ± 3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2 ± 5.8 vs 7.9 ± 4.3 ng/g, p = 0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8 ± 7 ms/mm Hg, PNN50: 24.9 ± 6.8%, rMSSD: 68 ± 22, LF/HF: 0.61 ± 0.28) in both sexes. After standing, 51.4% of subjects had a

  15. Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

    PubMed

    Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W; Davidson, Philip W; Myers, Gary J; Bovet, Pascal

    2015-03-23

    A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5

  16. Early Alcohol Exposure Disrupts Visual Cortex Plasticity in Mice

    PubMed Central

    Lantz, Crystal L.; Wang, Weili; Medina, Alexandre E.

    2012-01-01

    There is growing evidence that deficits in neuronal plasticity underlie the cognitive problems seen in fetal alcohol spectrum disorders (FASD). However, the mechanisms behind these deficits are not clear. Here we test the effects of early alcohol exposure on ocular dominance plasticity (ODP) in mice and the reversibility of these effects by phosphodiesterase (PDE) inhibitors. Mouse pups were exposed to 5 g/kg of 25% ethanol i.p. on postnatal days (P) 5, 7 and 9. This type of alcohol exposure mimics binge drinking during the third trimester equivalent of human gestation. To assess ocular dominance plasticity animals were monocularly deprived at P21 for 10 days, and tested using optical imaging of intrinsic signals. During the period of monocular deprivation animals were treated with vinpocetine (20mg/kg; PDE1 inhibitor), rolipram (1.25 mg/Kg; PDE4 inhibitor), vardenafil (3 mg/Kg; PDE5 inhibitor) or vehicle solution. Monocular deprivation resulted in the expected shift in ocular dominance of the binocular zone in saline controls but not in the ethanol group. While vinpocetine successfully restored ODP in the ethanol group, rolipram and vardenafil did not. However, when rolipram and vardenafil were given simultaneously ODP was restored. PDE4 and PDE5 are specific to cAMP and cGMP respectively, while PDE1 acts on both of these nucleotides. Our findings suggest that the combined activation of the cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in FASD models. PMID:22617459

  17. The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

    PubMed

    Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie; Glazer, Clara Helene; Giwercman, Aleksander; Ramlau-Hansen, Cecilia Høst; Hougaard, Karin Sørig; Høyer, Birgit Bjerre; Hærvig, Katia Keglberg; Petersen, Sesilje Bondo; Rylander, Lars; Specht, Ina Olmer; Toft, Gunnar; Bräuner, Elvira Vaclavik

    2016-12-01

    More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95

  18. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    PubMed

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  19. Prenatal Alcohol Exposure Increases Postnatal Acceptability of Nicotine Odor and Taste in Adolescent Rats

    PubMed Central

    Mantella, Nicole M.; Youngentob, Steven L.

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  20. DPOAEs in infants developmentally exposed to PCBs show two differently time spaced exposure sensitive windows.

    PubMed

    Koštiaková, Vladimíra; Moleti, Arturo; Wimmerová, Soňa; Jusko, Todd A; Palkovičová Murínová, Ľubica; Sisto, Renata; Richterová, Denisa; Kováč, Ján; Čonka, Kamil; Patayová, Henrieta; Tihányi, Juraj; Trnovec, Tomáš

    2016-10-01

    The study aim was to identify the timing of sensitive windows for ototoxicity related to perinatal exposure to PCBs. A total of 351 and 214 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 and 72 months, respectively, and distortion product otoacoustic emissions (DPOAEs) at 11 frequencies were recorded. Cord and child 6-, 16-, 45-, and 72- month blood samples were analyzed for PCB 153 concentration. The PCB 153 concentration-time profiles were approximated with a system model to calculate area under the PCB*time curves (AUCs) for specific time intervals (3 and 6 months for 45 and 72 months data, respectively). DPOAE amplitudes were correlated (Spearman) with cord serum PCB and AUCs, markers of prenatal and postnatal exposure, respectively. Two exposure critical windows were identified in infants, the first related to prenatal and early postnatal and the second to postnatal exposure to PCBs. Our data have shown tonotopicity, sexual dimorphism, and asymmetry in ototoxicity of PCBs. Copyright © 2016. Published by Elsevier Ltd.

  1. The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis

    PubMed Central

    Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie; Glazer, Clara Helene; Giwercman, Aleksander; Ramlau-Hansen, Cecilia Høst; Hougaard, Karin Sørig; Høyer, Birgit Bjerre; Hærvig, Katia Keglberg; Petersen, Sesilje Bondo; Rylander, Lars; Specht, Ina Olmer; Toft, Gunnar; Bräuner, Elvira Vaclavik

    2017-01-01

    BACKGROUND More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four

  2. Postnatal Innate Immune Development: From Birth to Adulthood

    PubMed Central

    Georgountzou, Anastasia; Papadopoulos, Nikolaos G.

    2017-01-01

    It is well established that adaptive immune responses are deficient in early life, contributing to increased mortality and morbidity. The developmental trajectories of different components of innate immunity are only recently being explored. Individual molecules, cells, or pathways of innate recognition and signaling, within different compartments/anatomical sites, demonstrate variable maturation patterns. Despite some discrepancies among published data, valuable information is emerging, showing that the developmental pattern of cytokine responses during early life is age and toll-like receptor specific, and may be modified by genetic and environmental factors. Interestingly, specific environmental exposures have been linked both to innate function modifications and the occurrence of chronic inflammatory disorders, such as respiratory allergies. As these conditions are on the rise, our knowledge on innate immune development and its modulating factors needs to be expanded. Improved understanding of the sequence of events associated with disease onset and persistence will lead toward meaningful interventions. This review describes the state-of-the-art on normal postnatal innate immune ontogeny and highlights research areas that are currently explored or should be further addressed. PMID:28848557

  3. Postnatal arsenic exposure and attention impairment in school children.

    PubMed

    Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

    2016-01-01

    additional evidence that postnatal arsenic exposure impairs neurological function in children. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Timing of Gestational Exposure to Zika Virus is Associated with Postnatal Growth Restriction in a Murine Model.

    PubMed

    Valentine, Gregory C; Seferovic, Maxim D; Fowler, Stephanie W; Major, Angela M; Gorchakov, Rodion; Berry, Rebecca; Swennes, Alton G; Murray, Kristy O; Suter, Melissa A; Aagaard, Kjersti M

    2018-06-11

    Vertical transmission of Zika virus (ZIKV) leads to infection of neuroprogenitor cells and destruction of brain parenchyma. Recent evidence suggests that the timing of infection as well as host factors may affect vertical transmission. As a result, congenital ZIKV infection may only become clinically apparent in the postnatal period. We sought to develop an outbred mouse model of ZIKV vertical transmission to determine if the timing of gestational ZIKV exposure yields phenotypic differences at birth and through adolescence. We hypothesized that later gestational inoculations would only become apparent in adolescence. To better recapitulate human exposures, timed pregnant Swiss-Webster dams (n=15) were subcutaneously inoculated with 1x10 4 PFU of first passage contemporary ZIKV HN16 strain or a mock injection on embryonic day 4, 8, or 12 with bioactive anti-interferon alpha receptor antibody administered in days preceding and proceeding inoculation. The antibody was given to prevent the robust type I interferon signaling cascade that make mice inherently resistant to ZIKV infection. At birth and adolescence (6 weeks of age) offspring were assessed for growth, brain weight and biparietal head diameters (BPD), and ZIKV viral levels by RT-PCR or in situ hybridization. Pups of ZIKV-infected dams infected at e4 and e8 but not e12 were growth restricted (p<0.003). Brain weights were significantly smaller at birth (p=0.01) for e8 ZIKV-exposed offspring. At 6 weeks of age, biparietal diameters (BPD) were smaller for all ZIKV exposed males and females (p<0.05), with e8 exposed males smallest by BPD and growth restriction measurements (weight >2 SD, p=0.0007). All pups and adolescent mice were assessed for ZIKV infection by RT-PCR. Analysis of all underweight pups reveled one to be positive for neuronal ZIKV infection by in situ hybridization, while a second moribund animal was diffusely positive at 8 days of age by ZIKV infectivity throughout the brain, kidneys and intestine

  5. Antenatal iron/folic acid supplements, but not postnatal care, prevents neonatal deaths in Indonesia: analysis of Indonesia Demographic and Health Surveys 2002/2003–2007 (a retrospective cohort study)

    PubMed Central

    Titaley, Christiana Rialine; Dibley, Michael John

    2012-01-01

    Objective This study aimed to assess the contribution of postnatal services to the risk of neonatal mortality, and the relative contributions of antenatal iron/folic acid supplements and postnatal care in preventing neonatal mortality in Indonesia. Design Retrospective cohort study. Setting and participants Data used in this study were the 2002–2007 Indonesia Demographic and Health Surveys, nationally representative surveys. The pooled data provided survival information of 26 591 most recent live-born infants within the 5-years prior to each interview. Primary outcomes Primary outcomes were early neonatal mortality, that is, deaths in the first week, and all neonatal mortality, that is, deaths in the first month of life. Exposures were antenatal iron/folic acid supplementation and postnatal care from days 1 to 7. Potential confounders were community, socio-economic status and birthing characteristics and perinatal healthcare. Cox regression was used to assess the association between study factors and neonatal mortality. Results Postnatal care services were not associated with newborn survival. Postnatal care on days 1–7 after birth did not reduce neonatal death (HR=1.00, 95% CI 0.55 to 1.83, p=1.00) and early postnatal care on day 1 was associated with an increased risk of early neonatal death (HR=1.27, 95% CI 0.69 to 2.32, p=0.44) possibly reflecting referral of ill newborns. Early postnatal care on day 1 was not protective for neonatal deaths on days 2–7 whether provided by doctors (HR 3.61, 95% CI 1.54 to 8.45, p<0.01), or by midwives or nurses (HR 1.38, 95% CI 0.53 to 3.57, p=0.512). In mothers who took iron/folic acid supplements during pregnancy, the risk of early neonatal death was reduced by 51% (HR=0.49, 95% CI 0.30 to 0.79, p<0.01). Conclusions We found no protective effect of postnatal care against neonatal deaths in Indonesia. However, important reductions in the risk of neonatal death were found for women who reported use of antenatal iron

  6. Exposure to a mildly aversive early life experience leads to prefrontal cortex deficits in the rat.

    PubMed

    Stamatakis, Antonios; Manatos, Vasileios; Kalpachidou, Theodora; Stylianopoulou, Fotini

    2016-11-01

    Aversive early life experiences in humans have been shown to result in deficits in the function of the prefrontal cortex (PFC). In an effort to elucidate possible neurobiological mechanisms involved, we investigated in rats, the effects of a mildly aversive early experience on PFC structure and function. The early experience involved exposure of rat pups during postnatal days (PND) 10-13 to a T-maze in which they search for their mother, but upon finding her are prohibited contact with her, thus being denied the expected reward (DER). We found that the DER experience resulted in adulthood in impaired PFC function, as assessed by two PFC-dependent behavioral tests [attention set-shifting task (ASST) and fear extinction]. In the ASST, DER animals showed deficits specifically in the intra-dimensional reversal shifts and a lower activation-as determined by c-Fos immunohistochemistry-of the medial orbital cortex (MO), a PFC subregion involved in this aspect of the task. Furthermore, the DER experience resulted in decreased glutamatergic neuron and dendritic spine density in the MO and infralimbic cortex (IL) in the adult brain. The decreased neuronal density was detected as early as PND12 and was accompanied by increased micro- and astroglia-density in the MO/IL.

  7. Massage therapy during early postnatal life promotes greater lean mass and bone growth, mineralization, and strength in juvenile and young adult rats.

    PubMed

    Chen, H; Miller, S; Shaw, J; Moyer-Mileur, L

    2009-01-01

    The objects of this study were to investigate the effects of massage therapy during early life on postnatal growth, body composition, and skeletal development in juvenile and young adult rats. Massage therapy was performed for 10 minutes daily from D6 to D10 of postnatal life in rat pups (MT, n=24). Body composition, bone area, mineral content, and bone mineral density were measured by dual energy X-ray absorptiometry (DXA); bone strength and intrinsic stiffness on femur shaft were tested by three-point bending; cortical and cancellous bone histomorphometric measurements were performed at D21 and D60. Results were compared to age- and gender-matched controls (C, n=24). D21 body weight, body length, lean mass, and bone area were significantly greater in the MT cohort. Greater bone mineral content was found in male MT rats; bone strength and intrinsic stiffness were greater in D60 MT groups. At D60 MT treatment promoted bone mineralization by increasing trabecular mineral apposition rate in male and endosteal mineral surface in females, and also improved micro-architecture by greater trabeculae width in males and decreasing trabecular separation in females. In summary, massage therapy during early life elicited immediate and prolonged anabolic effects on postnatal growth, lean mass and skeletal developmental in a gender-specific manner in juvenile and young adult rats.

  8. Medical students' attitudes towards early clinical exposure in Iran.

    PubMed

    Khabaz Mafinejad, Mahboobeh; Mirzazadeh, Azim; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

    2016-06-19

    This study was carried out to investigate the medical students' attitudes towards early clinical exposure at Tehran University of Medical Sciences. A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students' attitudes toward early clinical exposure. Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students' responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: "integration of theory and practice", "interaction with others and professional development" and "desire and motivation for learning medicine". Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students' understanding of the role they will play in the future as a physician.

  9. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers.

    PubMed

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-11-01

    The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l -1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (-11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (-69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  10. Early-life estrogen exposure and uterine pathogenesis: ?A model for gene-environment interactions

    EPA Science Inventory

    Aberrant cellular differentiation early in life can contribute to increased cancer risk later in life. In a classic model of this effect, female mice exposed on postnatal day (PND) 1-5 to the synthetic estrogen diethylstilbestrol (DES) have a high incidence of uterine carcinoma. ...

  11. Early age noise exposure increases loudness perception - A novel animal model of hyperacusis.

    PubMed

    Alkharabsheh, Ana'am; Xiong, Fen; Xiong, Binbin; Manohar, Senthilvelan; Chen, Guangdi; Salvi, Richard; Sun, Wei

    2017-04-01

    The neural mechanisms that give rise to hyperacusis, a reduction in loudness tolerance, are largely unknown. Some reports suggest that hyperacusis is linked to childhood hearing loss. However, the evidence for this is largely circumstantial. In order to rigorously test this hypothesis, we studied loudness changes in rats caused by intense noise exposure (12 kHz narrow band noise, 115 dB SPL, 4 h) at postnatal 16 days. Rats without noise exposure were used as controls. The exposed noise group (n = 7) showed a mean 40-50 dB hearing loss compared to the control group (n = 8) at high frequencies (>= 8 kHz) and less hearing loss at lower frequencies. Loudness was evaluated using sound reaction time and loudness response functions in an operant conditioning-based behavioral task using narrow-band noise (40-110 dB SPL, centered at 2, 4 and 12 kHz). Interestingly, the sound reaction time of the noise group was significantly shorter than the control group at supra-threshold levels. The average reaction time was less than 100 ms in the noise group at 100 dB SPL, which was three times shorter than the control group. Our results indicate that early noise-induced hearing loss leads to a significant increase of loudness, a behavior indicative of hyperacusis. Our results are consistent with clinical reports suggesting that hearing loss at an early age is a significant risk factor for hyperacusis. Published by Elsevier B.V.

  12. Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Axelstad, Marta, E-mail: maap@food.dtu.dk; Boberg, Julie; Hougaard, Karin Sorig

    Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T{sub 4}), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. Onmore » postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T{sub 4}) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T{sub 4} deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both

  13. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    PubMed

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  14. Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia.

    PubMed

    Durán-Carabali, L E; Arcego, D M; Odorcyk, F K; Reichert, L; Cordeiro, J L; Sanches, E F; Freitas, L D; Dalmaz, C; Pagnussat, A; Netto, C A

    2018-05-01

    Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.

  15. Early postnatal response of the spinal nucleus of the bulbocavernosus and target muscles to testosterone in male gerbils.

    PubMed

    Hadi Mansouri, S; Siegford, Janice M; Ulibarri, Catherine

    2003-05-14

    This study examined the response of the spinal nucleus of the bulbocavernosus (SNB) and the bulbocavernosus (BC) muscle, to testosterone in male Mongolian gerbils (Meriones unguiculatus) during the early postnatal period. Male gerbil pups were given testosterone propionate (TP) or vehicle for 2 days, then perfused on postnatal day (PND) 3, 5, 10 or 15. The BC and levator ani (LA) muscles were removed, weighed, and sectioned. Cross-sections of BC muscle fibers were measured and muscle fiber morphology examined. Spinal cords were removed and coronally sectioned in order to count and measure the SNB motoneurons. Following TP treatment, male pups of all ages had significantly heavier BC-LA muscles and larger fibers in the BC muscle compared to age-matched controls. The increase in muscle weight following TP treatment was greatest at PND10, while fiber size increased to a similar degree at all ages suggesting that hyperplasia as well as hypertrophy was responsible for the increase in muscle mass at this time. SNB motoneurons increased significantly in number and size with age and TP treatment. We hypothesize that the increase in SNB motoneuron number during normal ontogeny that can be augmented by TP treatment and represents an unusual means of establishing sexual dimorphism in the nervous system of a mammal through cell recruitment to the motor pool of a postnatal animal.

  16. Early-Life Exposure to Non-Nutritive Sweeteners and the Developmental Origins of Childhood Obesity: Global Evidence from Human and Rodent Studies.

    PubMed

    Archibald, Alyssa J; Dolinsky, Vernon W; Azad, Meghan B

    2018-02-10

    Non-nutritive sweeteners (NNS) are increasingly consumed by children and pregnant women around the world, yet their long-term health impact is unclear. Here, we review an emerging body of evidence suggesting that early-life exposure to NNS may adversely affect body composition and cardio-metabolic health. Some observational studies suggest that children consuming NNS are at increased risk for obesity-related outcomes; however, others find no association or provide evidence of confounding. Fewer studies have examined prenatal NNS exposure, with mixed results from different analytical approaches. There is a paucity of RCTs evaluating NNS in children, yielding inconsistent results that can be difficult to interpret due to study design limitations (e.g., choice of comparator, multifaceted interventions). The majority of this research has been conducted in high-income countries. Some rodent studies demonstrate adverse metabolic effects from NNS, but most have used extreme doses that are not relevant to humans, and few have distinguished prenatal from postnatal exposure. Most studies focus on synthetic NNS in beverages, with few examining plant-derived NNS or NNS in foods. Overall, there is limited and inconsistent evidence regarding the impact of early-life NNS exposure on the developmental programming of obesity and cardio-metabolic health. Further research and mechanistic studies are needed to elucidate these effects and inform dietary recommendations for expectant mothers and children worldwide.

  17. Role of Neurotrophins on Postnatal Neurogenesis in the Thalamus: Prenatal Exposure to Ethanol

    PubMed Central

    Mooney, Sandra M.; Miller, Michael W.

    2011-01-01

    A second wave of neuronal generation occurs in the ventrobasal nucleus of the rat thalamus (VB) during the first three postnatal weeks. The present study tested the hypotheses (1) that postnatal neurogenesis in the VB is neurotrophin-regulated and (2) that ethanol-induced changes in this proliferation are mediated by neurotrophins. The first studies examined the effects of neurotrophins on the numbers of cycling cells in ex vivo preparations of the VB from three-day-old rats. The proportion of cycling (Ki-67-positive) VB cells was higher in cultured thalamic slices treated with neurotrophins than in controls. Interestingly, this increase occurred with nerve growth factor (NGF) alone or with a combination of NGF and brain-derived neurotrophic factor (BDNF), but not with BDNF alone. Based on these data, the VBs from young offspring of pregnant rats fed an ethanol-containing or an isocaloric non-alcoholic liquid diet were examined between postnatal day (P) 1 and P31. Studies used enzyme-linked immunosorbent assays and immunoblots to explore the effects of ethanol on the expression of neurotrophins, their receptors, and representative signaling proteins. Ethanol altered the expression of neurotrophins and receptors throughout the first postnatal month. Expression of NGF increased, but there was no change in the expression of BDNF. The high affinity receptors (TrkA and TrkB) were unchanged but ethanol decreased expression of the low affinity receptor, p75. One downstream signaling protein, extracellular signal-regulated kinase (ERK), decreased but Akt expression was unchanged. Thus, postnatal cell proliferation in the VB of young rat pups is neurotrophin-responsive and is affected by ethanol. PMID:21277941

  18. Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

    PubMed

    Doyle, Lex W; Cheong, Jeanie L; Ehrenkranz, Richard A; Halliday, Henry L

    2017-10-24

    Bronchopulmonary dysplasia remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to prevent or treat bronchopulmonary dysplasia because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of systemic postnatal corticosteroids commenced within the first seven days of life for preterm infants at risk of developing bronchopulmonary dysplasia. For the 2017 update, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21 February 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 2013 to 21 February 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. For this review, we selected RCTs examining systemic postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants. Most studies evaluated the use of dexamethasone, but we also included studies that assessed hydrocortisone, even when used primarily for management of hypotension. We used the GRADE approach to assess the quality of evidence.We extracted and analysed data regarding clinical outcomes that included mortality, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, failure to extubate, complications during primary hospitalisation, and long-term health outcomes. We included 32 RCTs enrolling a total of 4395 participants. The overall risk of bias of included studies was probably low, as all were RCTs, and most trials used rigorous methods. Investigators reported significant benefits for the following outcomes overall: lower rates of failure to extubate, decreased

  19. Medical students’ attitudes towards early clinical exposure in Iran

    PubMed Central

    Khabaz Mafinejad, Mahboobeh; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

    2016-01-01

    Objectives This study was carried out to investigate the medical students’ attitudes towards early clinical exposure at Tehran University of Medical Sciences. Methods A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students’ attitudes toward early clinical exposure. Results Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students’ responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: “integration of theory and practice”, “interaction with others and professional development” and “desire and motivation for learning medicine”. Conclusions Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students’ understanding of the role they will play in the future as a physician. PMID:27318794

  20. Postnatal hyperoxia or DEHP exposure leads to growth restriction and delayed lung development in newborn rats.

    PubMed

    Liang, Zhong-Jie; Wu, Qiu-Ping; Chen, Bei-Tao; Lin, Zhen-Lang; Lin, Jing; Chen, Shang-Qin

    2018-02-01

    Di-(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in many medical devices. We previously showed that maternal DEHP exposure led to restricted growth and delayed lung maturation in newborn rats. As oxygen toxicity continues to be a major risk factor for bronchopulmonary dysplasia, the aim of this study was to examine the effect of hyperoxia, DEHP or DEHP combined with hyperoxia on the growth and lung maturation of newborn rats. Newborn rats received DEHP injection, hyperoxia exposure or DEHP injection combined with hyperoxia exposure for one week or two weeks. A control group received an equal volume of vehicle and was maintained in room air. Hyperoxia and hyperoxia + DEHP exposure for one week led to growth failure in newborn rats. Pups in the hyperoxia group showed catch-up growth after being maintained in room air for an additional 7 days but this was not the case with the latter group, which continued to receive DEHP. Hyperoxia and DEHP both delayed lung development, as evidenced by decreased radial alveolar count. Quantitative RT-PCR showed that hyperoxia decreased the transcripts of VEGF, VEGFR-2 and eNOS on days 7 and 14, and DEHP exposure alone also led to decreased expression of VEGF gene in 14-day-old rat pups. Postnatal hyperoxia and/or DEHP exposure lead to growth restriction and delayed lung alveolar development. The VEGF gene expression was altered and may be involved as one of the possible molecular mechanisms. Copyright © 2017. Published by Elsevier B.V.

  1. Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stringari, James; Nunes, Adriana K.C.; Franco, Jeferson L.

    2008-02-15

    During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinkingmore » water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F{sub 2}-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F{sub 2}-isoprostanes levels at all time points. Significant negative correlations were found between F{sub 2}-isoprostanes and GSH, as well as between F{sub 2}-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral

  2. Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

    PubMed Central

    Stringari, James; Nunes, Adriana KC; Franco, Jeferson L; Bohrer, Denise; Garcia, Solange C; Dafre, Alcir L; Milatovic, Dejan; Souza, Diogo O; Rocha, João BT; Aschner, Michael; Farina, Marcelo

    2010-01-01

    During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/L, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PNDs) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F2-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F2-isoprostanes levels at all time points. Significant negative correlations were found between F2-isoprostanes and GSH, as well as between F2-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even

  3. Endogenous Opioids as Substrates for Ethanol Intake in the Neonatal Rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period

    PubMed Central

    Bordner, Kelly; Deak, Terrence

    2015-01-01

    Background Despite considerable knowledge that prenatal ethanol exposure can lead to devastating effects on the developing fetus, alcohol consumption by pregnant women remains strikingly prevalent. Both clinical and basic research has suggested that, in addition to possible physical, behavioral, and cognitive deficits, gestational exposure to alcohol may lead to an increased risk for the development of later alcohol-related use and abuse disorders. The current work sought to characterize alterations in endogenous opioid signaling peptides and gene expression produced by ethanol exposure during the last days of gestation. Methods Experimental subjects were 4-, 8-, and 12-day old infant rats obtained from pregnant females that were given daily intubations of 0, 1, or 2 g/kg ethanol during the last few days of gestation (GD17-20). Using real-time RT-PCR, western blotting analysis, and enzyme immunoassays, we examined mRNA and protein for three opioid receptors and ligands in the nucleus accumbens, ventral tegmental area, and hypothalamus. Results Three main trends emerged - (1) mRNA for the majority of factors were found to upregulate across each of the three postnatal ages assessed, indicative of escalating ontogenetic expression of opioid-related genes; (2) prenatal ethanol significantly reduced many opioid peptides, suggesting a possible mechanism by which prenatal exposure can affect future responsiveness towards ethanol; and (3) the nucleus accumbens emerged as a key site for ethanol-dependent effects, suggesting a potential target for additional assessment and intervention towards understanding the ethanol's ability to program the developing brain. Conclusion We provide a global assessment of relatively long-term changes in both opioid gene expression and protein following exposure to only moderate amounts of ethanol during a relatively short window in the prenatal period. These results suggest that, while continuing to undergo ontogenetic changes, the infant

  4. Endogenous opioids as substrates for ethanol intake in the neonatal rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period.

    PubMed

    Bordner, Kelly; Deak, Terrence

    2015-09-01

    Despite considerable knowledge that prenatal ethanol exposure can lead to devastating effects on the developing fetus, alcohol consumption by pregnant women remains strikingly prevalent. Both clinical and basic research has suggested that, in addition to possible physical, behavioral, and cognitive deficits, gestational exposure to alcohol may lead to an increased risk for the development of later alcohol-related use and abuse disorders. The current work sought to characterize alterations in endogenous opioid signaling peptides and gene expression produced by ethanol exposure during the last days of gestation. Experimental subjects were 4-, 8-, and 12-day old infant rats obtained from pregnant females that were given daily intubations of 0, 1, or 2g/kg ethanol during the last few days of gestation (GDs 17-20). Using real-time RT-PCR, western blotting analysis, and enzyme immunoassays, we examined mRNA and protein for three opioid receptors and ligands in the nucleus accumbens, ventral tegmental area, and hypothalamus. Three main trends emerged - (1) mRNA for the majority of factors was found to upregulate across each of the three postnatal ages assessed, indicative of escalating ontogenetic expression of opioid-related genes; (2) prenatal ethanol significantly reduced many opioid peptides, suggesting a possible mechanism by which prenatal exposure can affect future responsiveness towards ethanol; and (3) the nucleus accumbens emerged as a key site for ethanol-dependent effects, suggesting a potential target for additional assessment and intervention towards understanding the ethanol's ability to program the developing brain. We provide a global assessment of relatively long-term changes in both opioid gene expression and protein following exposure to only moderate amounts of ethanol during a relatively short window in the prenatal period. These results suggest that, while continuing to undergo ontogenetic changes, the infant brain is sensitive to prenatal ethanol

  5. Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

    PubMed

    Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

    2018-05-09

    Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  6. Monoamine Oxidases Regulate Telencephalic Neural Progenitors in Late Embryonic and Early Postnatal Development

    PubMed Central

    Cheng, Aiwu; Scott, Anna L.; Ladenheim, Bruce; Chen, Kevin; Ouyang, Xin; Lathia, Justin D.; Mughal, Mohamed; Cadet, Jean Lud; Mattson, Mark P.; Shih, Jean C.

    2010-01-01

    Monoamine neurotransmitters play major roles in regulating a range of brain functions in adults and increasing evidence suggests roles for monoamines in brain development. Here we show that mice lacking the monoamine metabolic enzymes MAO A and MAO B (MAO AB-deficient mice) exhibit diminished proliferation of neural stem cells (NSC) in the developing telencephalon beginning in late gestation [embryonic day (E) 17.5], a deficit that persists in neonatal and adult mice. These mice showed significantly increased monoamine levels and anxiety-like behaviors as adults. Assessments of markers of intermediate progenitor cells (IPC) and mitosis showed that NSC in the subventricular zone (SVZ), but not in the ventricular zone, are reduced in MAO AB-deficient mice. A developmental time course of monoamines in frontal cortical tissues revealed increased serotonin levels as early as E14.5, and a further large increase was found between E17.5 and postnatal day 2. Administration of an inhibitor of serotonin synthesis (parachlorophenylalanine) between E14.5 and E19.5 restored the IPC numbers and SVZ thickness, suggesting the role of serotonin in the suppression of IPC proliferation. Studies of neurosphere cultures prepared from the telencephalon at different embryonic and postnatal ages showed that serotonin stimulates proliferation in wild-type, but not in MAO AB-deficient, NSC. Together, these results suggest that a MAO-dependent long-lasting alteration in the proliferation capacity of NSC occurs late in embryonic development and is mediated by serotonin. Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain. PMID:20702706

  7. Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice

    PubMed Central

    Hougaard, Karin S; Jensen, Keld A; Nordly, Pernille; Taxvig, Camilla; Vogel, Ulla; Saber, Anne T; Wallin, Håkan

    2008-01-01

    Background Results from epidemiological studies indicate that particulate air pollution constitutes a hazard for human health. Recent studies suggest that diesel exhaust possesses endocrine activity and therefore may affect reproductive outcome. This study in mice aimed to investigate whether exposure to diesel exhaust particles (DEP; NIST 2975) would affect gestation, postnatal development, activity, learning and memory, and biomarkers of transplacental toxicity. Pregnant mice (C57BL/6; BomTac) were exposed to 19 mg/m3 DEP (~1·106 particles/cm3; mass median diameter ≅ 240 nm) on gestational days 9–19, for 1 h/day. Results Gestational parameters were similar in control and diesel groups. Shortly after birth, body weights of DEP offspring were slightly lower than in controls. This difference increased during lactation, so by weaning the DEP exposed offspring weighed significantly less than the control progeny. Only slight effects of exposure were observed on cognitive function in female DEP offspring and on biomarkers of exposure to particles or genotoxic substances. Conclusion In utero exposure to DEP decreased weight gain during lactation. Cognitive function and levels of biomarkers of exposure to particles or to genotoxic substances were generally similar in exposed and control offspring. The particle size and chemical composition of the DEP and differences in exposure methods (fresh, whole exhaust versus aged, resuspended DEP) may play a significant role on the biological effects observed in this compared to other studies. PMID:18331653

  8. Genocide Exposure and Subsequent Suicide Risk: A Population-Based Study

    PubMed Central

    Levine, Stephen Z.; Levav, Itzhak; Yoffe, Rinat; Becher, Yifat; Pugachova, Inna

    2016-01-01

    The association between periods of genocide-related exposures and suicide risk remains unknown. Our study tests that association using a national population-based study design. The source population comprised of all persons born during1922-1945 in Nazi-occupied or dominated European nations, that immigrated to Israel by 1965, were identified in the Population Register (N = 220,665), and followed up for suicide to 2014, totaling 16,953,602 person-years. The population was disaggregated to compare a trauma gradient among groups that immigrated before (indirect, n = 20,612, 9%); during (partial direct, n = 17,037, 8%); or after (full direct, n = 183,016, 83%) exposure to the Nazi era. Also, the direct exposure groups were examined regarding pre- or post-natal exposure periods. Cox regression models were used to compute Hazard Ratios (HR) of suicide risk to compare the exposure groups, adjusting for confounding by gender, residential SES and history of psychiatric hospitalization. In the total population, only the partial direct exposure subgroup was at greater risk compared to the indirect exposure group (HR = 1.73, 95% CI, 1.10, 2.73; P < .05). That effect replicated in six sensitivity analyses. In addition, sensitivity analyses showed that exposure at ages 13 plus among females, and follow-up by years since immigration were associated with a greater risk; whereas in utero exposure among persons with no psychiatric hospitalization and early postnatal exposure among males were at a reduced risk. Tentative mechanisms impute biopsychosocial vulnerability and natural selection during early critical periods among males, and feelings of guilt and entrapment or defeat among females. PMID:26901411

  9. Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants.

    PubMed

    Vollmer, Brigitte; Seibold-Weiger, Karin; Schmitz-Salue, Christine; Hamprecht, Klaus; Goelz, Rangmar; Krageloh-Mann, Ingeborg; Speer, Christian P

    2004-04-01

    In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.

  10. The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis

    PubMed Central

    Perkins, Amy E.; Fadel, Jim R.; Kelly, Sandra J.

    2015-01-01

    Fetal alcohol spectrum disorders (FASD) affect 2–5% of children. FASD have been shown to cause damage to multiple brain regions, but damage to the hippocampus specifically may explain deficits in learning and memory that are hallmark symptoms of FASD. The acetylcholine neurotransmitter system is a major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intragastric intubation to developing male rat pups (postnatal day [PD] 2–10; ethanol-treated [ET]), with controls receiving a sham intubation (IC) or no treatment (NC). In Experiment 1, in vivo microdialysis was used to measure acetylcholine efflux in adolescents (PD 32–35). During microdialysis, the effects of a high K+/Ca2+ aCSF solution (PD 32–33) and an acute galantamine (acetylcholinesterase [AChE] inhibitor) injection (2.0 mg/kg; PD 34–35) on acetylcholine efflux were measured. Alcohol-exposed animals did not differ in acetylcholine efflux at baseline. However, alcohol-exposed animals had a decrease in K+/Ca2+-induced acetylcholine efflux compared to non-treated controls, and an enhanced acetylcholine response to galantamine compared to both control groups. Experiment 2 tested whether chronic administration of galantamine (2.0 mg/kg; PD 11–30) could attenuate alcohol-induced learning deficits in the context pre-exposure facilitation effect (CPFE; PD 30–32). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Immunohistochemistry was used to measure expression of choline acetyltransferase (ChAT; medial septum), vesicular acetylcholine transporter (vAChT; ventral CA1), and the alpha7 nicotinic acetylcholine receptor (α7 nAChR; ventral CA1) following microdialysis (Exp. 1) or chronic galantamine and behavioral testing (Exp. 2). Neither alcohol exposure nor behavioral testing significantly altered the density of vAChT or α7 nAChRs in the ventral CA1 region of the

  11. Postnatal dietary fatty acid composition permanently affects the structure of hypothalamic pathways controlling energy balance in mice.

    PubMed

    Schipper, Lidewij; Bouyer, Karine; Oosting, Annemarie; Simerly, Richard B; van der Beek, Eline M

    2013-12-01

    We previously reported that dietary lipid quality during early life can have long-lasting effects on metabolic health and adiposity. Exposure to a postnatal diet with low dietary omega-6 (n-6) or high omega-3 (n-3) fatty acid (FA) content resulted in reduced body fat accumulation when challenged with a moderate Western-style diet (WSD) beginning in adolescence. We determined whether this programming effect is accompanied by changes in hypothalamic neural projections or modifications in the postnatal leptin surge, which would indicate the altered development of hypothalamic circuits that control energy balance. Neonatal mice were subjected to a control diet (CTR) or experimental diet with altered relative n-6 and n-3 FA contents [ie, a diet with a relative reduction in n-6 fatty acid (LOW n-6) or a diet with a relative increase in n-3 fatty acid (HIGH n-3) compared with the CTR from postnatal day (PN) 2 to 42]. Compared with CTR mice, mice fed a LOW n-6 or HIGH n-3 during postnatal life showed significant reductions in the density of both orexigenic and anorexigenic neural projections to the paraventricular nucleus of the hypothalamus at PN 28. These impairments persisted into adulthood and were still apparent after the WSD challenge between PNs 42 and 98. However, the neuroanatomical changes were not associated with changes in the postnatal leptin surge. Although the exact mechanism remains to be elucidated, our data indicate that the quality of dietary FA during postnatal life affects the development of the central regulatory circuits that control energy balance and may do so through a leptin-independent mechanism.

  12. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour

    PubMed Central

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C.; Hughes, Ieuan A.; Acerini, Carlo L.

    2016-01-01

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. PMID:26833843

  13. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    PubMed

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. © 2016 The Author(s).

  14. Pre- and post-natal exposure to antibiotics and the development of eczema, recurrent wheezing and atopic sensitization in children up to the age of 4 years.

    PubMed

    Dom, S; Droste, J H J; Sariachvili, M A; Hagendorens, M M; Oostveen, E; Bridts, C H; Stevens, W J; Wieringa, M H; Weyler, J J

    2010-09-01

    Little data are available on the relationship between indirect antibiotic exposure of the child in utero or during lactation and allergic diseases. On the other hand, several studies have been conducted on the association with direct post-natal antibiotic exposure, but the results are conflicting. The aim of this study was to investigate pre- and post-natal antibiotic exposure and the subsequent development of eczema, recurrent wheeze and atopic sensitization in children up to the age of 4 years. We conducted an aetiologic study in 773 children based on a prospective birth cohort project in which environmental and health information were collected using questionnaires. Antibiotic exposure was assessed as maternal antibiotic intake during pregnancy and during lactation and as medication intake of the child. The chronology of exposures and outcomes was taken into account during the data processing. At the age of 1 and 4 years, a blood sample was taken for the quantification of specific IgE. Prenatal antibiotic exposure was significantly positively associated with eczema, whereas no association was found with recurrent wheeze and atopic sensitization. We found a positive, although statistically not significant, association between antibiotic exposure through breastfeeding and recurrent wheeze. Neither eczema nor atopic sensitization was significantly associated with antibiotic exposure through breastfeeding. Finally, we observed a negative association between the use of antibiotics in the first year of life and eczema and atopic sensitization, and also between antibiotic use after the first year of life and recurrent wheeze, eczema and atopic sensitization. Indirect exposure to antibiotics (in utero and during lactation) increases the risk for allergic symptoms in children, while direct exposure to antibiotics appears to be protective. The biological mechanisms underlying these findings still need to be elucidated.

  15. The effects of delivery route and anesthesia type on early postnatal weight loss in newborns: the role of vasoactive hormones.

    PubMed

    Okumus, Nurullah; Atalay, Yildiz; Onal, Eray E; Turkyilmaz, Canan; Senel, Saliha; Gunaydin, Berrin; Pasaoglu, Hatice; Koc, Esin; Ergenekon, Ebru; Unal, Suna

    2011-01-01

    To investigate the effects of delivery route and maternal anesthesia type and the roles of vasoactive hormones on early postnatal weight loss in term newborns. Ninety-four term infants delivered vaginally (group 1, n=31), cesarean section (C/S) with general anesthesia (GA) (group 2, n=29), and C/S with epidural anesthesia (EA) (group 3, n=34) were included in this study. All infants were weighed at birth and on the second day of life and intravenous (IV) fluid infused to the mothers for the last 6 h prior to delivery was recorded. Serum electrolytes, osmolality, N-terminal proANP (NT-proANP), brain natriuretic peptide (BNP), aldosterone and plasma antidiuretic hormone (ADH) concentrations were measured at cord blood and on the second day of life. Our research showed that postnatal weight loss of infants was higher in C/S than vaginal deliveries (5.7% vs. 1.3%) (p < 0.0001) and in EA group than GA group (6.8% vs. 4.3%) (p < 0.0001). Postnatal weight losses were correlated with IV fluid volume infused to the mothers for the last 6 h prior to delivery (R = 0.814, p = 0.000) and with serum NT-proANP (R = 0.418, p = 0.000), BNP (R = 0.454, p = 0.000), and ADH (R = 0.509, p = 0.000) but not with aldosterone concentrations (p > 0.05). Large amounts of IV fluid given to the mothers who were applied EA prior to the delivery affect their offsprings' postnatal weight loss via certain vasoactive hormones.

  16. Understanding How Postnatal Depression Screening and Early Intervention Work in the Real World - A Singaporean Perspective.

    PubMed

    Lee, Theresa My; Bautista, Dianne; Chen, Helen Y

    2016-10-01

    Postnatal depression is a major public health problem with clearly established adverse effects in child outcomes. This study examines the 4-year outcomes of a screening and early intervention programme, in relation to improvement in symptoms, functioning and health quality of life. Women were prospectively recruited up to 6 months postdelivery, using the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool. High-scorers (EPDS >13), were offered psychiatric consultation, and those with borderline scores (EPDS 10-12) were provided counselling, and offered follow-up phone counselling by the assigned case manager. Outcome measures were obtained at baseline, and at 6 months or discharge if earlier, for levels of symptoms, functioning, and health quality of life. From 2008 to 2012, 5245 women were screened, with 307 (5.9%) women with EPDS >13 receiving intervention. Of these, 70.0% had depression, 4.6% anxiety and 3.4% psychosis. In the depression subgroup, the net change was improvement of 93.4% EPDS symptom scores, 92.2% Global Assessment of Functioning (GAF) scores, and 88.3% visual analogue scale (EQ VAS) health quality of life scores. Outcome scores across diagnostic categories demonstrated median changes of 10 points on EPDS, 20 points on GAF, and 25 points on EQ VAS, reflecting 73.9%, 36.4% and 41.7% change from baseline scores. Women with psychosis showed the biggest (80.0%) relative change in GAF functioning scores from baseline to discharge but had the lowest median change in EPDS symptom scores. A screening and intervention programme rightly-sited within an obstetric setting can improve clinical outcomes because of early detection and intervention.

  17. Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice

    PubMed Central

    Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

    2015-01-01

    Depression is a serious mental disorder that affects a person’s mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression. PMID:25875952

  18. Postnatal loss of hap1 reduces hippocampal neurogenesis and causes adult depressive-like behavior in mice.

    PubMed

    Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

    2015-04-01

    Depression is a serious mental disorder that affects a person's mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression.

  19. Methylxanthines during pregnancy and early postnatal life.

    PubMed

    Adén, Ulrika

    2011-01-01

    World-wide, many fetuses and infants are exposed to methylxanthines via maternal consumption of coffee and other beverages containing these substances. Methylxanthines (caffeine, theophylline and aminophylline) are also commonly used as a medication for apnea of prematurity.The metabolism of methylxanthines is impaired in pregnant women, fetuses and neonates, leading to accumulating levels thereof. Methylxanthines readily passes the placenta barrier and enters all tissues and thus may affect the fetus/newborn at any time during pregnancy or postnatal life, given that the effector systems are mature.At clinically relevant doses, the major effector system for methylxanthines is adenosine receptors. Animal studies suggest that adenosine receptors in the cardiovascular, respiratory and immune system are developed at birth, but that cerebral adenosine receptors are not fully functional. Furthermore animal studies have shown protective positive effects of methylxanthines in situations of hypoxia/ischemia in neonates. Similarly, a positive long-term effect on lung function and CNS development was found in human preterm infants treated with high doses of caffeine for apneas. There is now evidence that the overall benefits from methylxanthine therapy for apnea of prematurity outweigh potential short-term risks.On the other hand it is important to note that experimental studies have indicated that long-term effects of caffeine during pregnancy and postnatally may include altered behavior and altered respiratory control in the offspring, although there is currently no human data to support this.Some epidemiology studies have reported negative effects on pregnancy and perinatal outcomes related to maternal ingestion of high doses of caffeine, but the results are inconclusive. The evidence base for adverse effects of caffeine in first third of pregnancy are stronger than for later parts of pregnancy and there is currently insufficient evidence to advise women to restrict

  20. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yue; Xie, Changchun; Murphy, Susan K.

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  1. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE PAGES

    Li, Yue; Xie, Changchun; Murphy, Susan K.; ...

    2015-06-26

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  2. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martinez–Arguelles, D.B.; Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4; McIntosh, M.

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressuremore » in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.« less

  3. Effects of prenatal and postnatal depression, and maternal stroking, at the glucocorticoid receptor gene.

    PubMed

    Murgatroyd, C; Quinn, J P; Sharp, H M; Pickles, A; Hill, J

    2015-05-05

    In animal models, prenatal and postnatal stress is associated with elevated hypothalamic-pituitary axis (HPA) reactivity mediated via altered glucocorticoid receptor (GR) gene expression. Postnatal tactile stimulation is associated with reduced HPA reactivity mediated via increased GR gene expression. In this first study in humans to examine the joint effects of prenatal and postnatal environmental exposures, we report that GR gene (NR3C1) 1-F promoter methylation in infants is elevated in the presence of increased maternal postnatal depression following low prenatal depression, and that this effect is reversed by self-reported stroking of the infants by their mothers over the first weeks of life.

  4. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep

    PubMed Central

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

  5. Prenatal and postnatal exposure to DDT by breast milk analysis in Canary Islands.

    PubMed

    Vall, Oriol; Gomez-Culebras, Mario; Puig, Carme; Rodriguez-Carrasco, Ernesto; Gomez Baltazar, Arelis; Canchucaja, Lizzeth; Joya, Xavier; Garcia-Algar, Oscar

    2014-01-01

    The use of p,p'-dichlorodiphenyltrichloroethane (DDT) has been banned since the late 1970s due to its toxicity. However, its long half-life makes it persistent in the environment and, consequently, almost everyone has DDT residues in the body. Human milk constitutes an ideal non-conventional matrix to investigate environmental chronic exposure to organochlorine compounds (OCs) residues. The study aimed to identify potential population risk factors of exposure to DDT due to the proximity to countries where it is still used. Seventy-two consecutive lactating women were prospectively included in Tenerife, Canary Islands (Spain). A validated questionnaire was used to obtain socioeconomic, demographics data, and daily habits during pregnancy. DDT levels in breast milk were measured by gas chromatography with-electron capture detector (GC-ECD). Anthropometrics measurements in newborns were obtained. Thirty-four out of 72 (47.2%) of the analysed milk samples presented detectable levels of DDT (mean: 0.92 ng/g), ranging between 0.08 to 16.96 ng/g. The socio-demographic variables did not significantly differ between detectable DDT and non-detectable DDT groups. We found positive association between DDT levels and vegetables (OR (95%CI): 1.23 (1.01-1.50)) and poultry meat (OR (95%CI): 2.05 (1.16-3.60)) consumption, and also between the presence of DDT in breast milk and gestational age (OR (95%CI): 0.59 (0.40-0.90)). DDT is present in breast milk of women at the time of delivery. Residual levels and the spread from countries still using DDT explain DDT detection from vegetables and from animal origin food. The presence of this compound in breast milk represents a pre- and postnatal exposure hazard for foetuses and infants due to chronic bioaccumulation and poor elimination, with possible deleterious effects on health. This data should be used to raise awareness of the risks of OCs exposure and to help establish health policies in order to avoid its use worldwide and thus, to

  6. Prenatal and Postnatal Exposure to DDT by Breast Milk Analysis in Canary Islands

    PubMed Central

    Vall, Oriol; Gomez-Culebras, Mario; Puig, Carme; Rodriguez-Carrasco, Ernesto; Gomez Baltazar, Arelis; Canchucaja, Lizzeth; Joya, Xavier; Garcia-Algar, Oscar

    2014-01-01

    Introduction The use of p,p′-dichlorodiphenyltrichloroethane (DDT) has been banned since the late 1970s due to its toxicity. However, its long half-life makes it persistent in the environment and, consequently, almost everyone has DDT residues in the body. Human milk constitutes an ideal non-conventional matrix to investigate environmental chronic exposure to organochlorine compounds (OCs) residues. The study aimed to identify potential population risk factors of exposure to DDT due to the proximity to countries where it is still used. Methods Seventy-two consecutive lactating women were prospectively included in Tenerife, Canary Islands (Spain). A validated questionnaire was used to obtain socioeconomic, demographics data, and daily habits during pregnancy. DDT levels in breast milk were measured by gas chromatography with-electron capture detector (GC-ECD). Anthropometrics measurements in newborns were obtained. Results Thirty-four out of 72 (47.2%) of the analysed milk samples presented detectable levels of DDT (mean: 0.92 ng/g), ranging between 0.08 to 16.96 ng/g. The socio-demographic variables did not significantly differ between detectable DDT and non-detectable DDT groups. We found positive association between DDT levels and vegetables (OR (95%CI): 1.23 (1.01–1.50)) and poultry meat (OR (95%CI): 2.05 (1.16–3.60)) consumption, and also between the presence of DDT in breast milk and gestational age (OR (95%CI): 0.59 (0.40–0.90)). Conclusions DDT is present in breast milk of women at the time of delivery. Residual levels and the spread from countries still using DDT explain DDT detection from vegetables and from animal origin food. The presence of this compound in breast milk represents a pre- and postnatal exposure hazard for foetuses and infants due to chronic bioaccumulation and poor elimination, with possible deleterious effects on health. This data should be used to raise awareness of the risks of OCs exposure and to help establish health policies

  7. Prenatal Exposure to Phenols and Growth in Boys

    PubMed Central

    Philippat, Claire; Botton, Jérémie; Calafat, Antonia M.; Ye, Xiaoyun; Charles, Marie-Aline; Slama, Rémy

    2016-01-01

    Background Phenols interact with nuclear receptors implicated in growth and adipogenesis regulation. Only a few studies have explored their effects on growth in humans. Objectives We studied the associations of maternal exposure to phenols during pregnancy with prenatal and postnatal growth of male newborns. Methods Within a cohort of women recruited during pregnancy, we selected 520 mother–son pairs and quantified 9 phenols in spot urine samples collected during pregnancy. We used ultrasonography during pregnancy, together with birth measurements, to assess fetal growth. We modeled individual postnatal growth trajectories from repeated measures of weight and height in the first 3 years of life. Results Triclosan concentration was negatively associated with growth parameters measured at the third ultrasound examination but not earlier in pregnancy. At birth, this phenol tended to be negatively associated with head circumference (−1.2 mm for an interquartile range [IQR] increase in ln-transformed triclosan concentration [95% confidence interval = −2.6 to 0.3]) but not with weight or height. Parabens were positively associated with weight at birth. This positive association remained for 3 years for methylparaben (β = 193 g [−4 to 389]) for an IQR increase in ln-transformed concentrations. Conclusion We relied on only 1 spot urine sample to assess exposure; because of the high variability in phenol urinary concentrations reported during pregnancy, using only 1 sample may result in exposure misclassification, in particular for bisphenol A. Our study suggested associations between prenatal exposure to parabens and triclosan and prenatal or early postnatal growth. PMID:25061923

  8. Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

    PubMed

    Claus Henn, Birgit; Austin, Christine; Coull, Brent A; Schnaas, Lourdes; Gennings, Chris; Horton, Megan K; Hernández-Ávila, Mauricio; Hu, Howard; Téllez-Rojo, Martha Maria; Wright, Robert O; Arora, Manish

    2018-02-01

    Associations between manganese (Mn) and neurodevelopment may depend on dose and exposure timing, but most studies cannot measure exposure variability over time well. We apply temporally informative tooth-matrix biomarkers to uncover windows of susceptibility in early life when Mn is associated with visual motor ability in childhood. We also explore effect modification by lead (Pb) and child sex. Participants were drawn from the ELEMENT (Early Life Exposures in MExico and NeuroToxicology) longitudinal birth cohort studies. We reconstructed dose and timing of prenatal and early postnatal Mn and Pb exposures for 138 children by analyzing deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. Neurodevelopment was assessed between 6 and 16 years of age using the Wide Range Assessment of Visual Motor Abilities (WRAVMA). Mn associations with total WRAVMA scores and subscales were estimated with multivariable generalized additive mixed models. We examined Mn interactions with Pb and child sex in stratified models. Levels of dentine Mn were highest in the second trimester and declined steeply over the prenatal period, with a slower rate of decline after birth. Mn was positively associated with visual spatial and total WRAVMA scores in the second trimester, among children with lower (< median) tooth Pb levels: one standard deviation (SD) increase in ln-transformed dentine Mn at 150 days before birth was associated with a 0.15 [95% CI: 0.04, 0.26] SD increase in total score. This positive association was not observed at high Pb levels. In contrast to the prenatal period, significant negative associations were found in the postnatal period from ~ 6 to 12 months of age, among boys only: one SD increase in ln-transformed dentine Mn was associated with a 0.11 [95% CI: - 0.001, - 0.22] to 0.16 [95% CI: - 0.04, - 0.28] SD decrease in visual spatial score. Using tooth-matrix biomarkers with fine scale temporal profiles of exposure, we found discrete

  9. Influence of prenatal and postnatal growth on intellectual functioning in school-aged children.

    PubMed

    Pongcharoen, Tippawan; Ramakrishnan, Usha; DiGirolamo, Ann M; Winichagoon, Pattanee; Flores, Rafael; Singkhornard, Jintana; Martorell, Reynaldo

    2012-05-01

    To assess the relative influence of size at birth, infant growth, and late postnatal growth on intellectual functioning at 9 years of age. A follow-up, cross-sectional study. Three districts in Khon Kaen province, northeast Thailand. A total of 560 children, or 92% of former participants of a trial of iron and/or zinc supplementation during infancy. Prenatal (size at birth), early infancy (birth to 4 months), late infancy (4 months to 1 year), and late postnatal (1 to 9 years) growth. Multiple-stage least squares analyses were used to generate uncorrelated residuals of postnatal growth. Intellectual functioning was measured at 9 years using the Wechsler Intelligence Scale for Children and the Raven's Colored Progressive Matrices (Pearson). Analyses included adjustment for maternal, household, and school characteristics. Significant relationships were found between growth and IQ (Wechsler Intelligence Scale for children, third edition, Thai version), but only up to 1 year of age; overall, growth was not related to the Raven's Colored Progressive Matrices. The strongest and most consistent relationships were with length (birth, early infancy, and late infancy); for weight, only early infancy gain was consistently related to IQ. Head circumference at birth was not collected routinely; head circumference at 4 months (but not head circumference growth thereafter) was related to IQ. Late postnatal growth was not associated with any outcome. Physical growth in early infancy (and, to a lesser extent, physical growth in late infancy and at birth) is associated with IQ at 9 years of age. Early infancy may be a critical window for human development.

  10. Notch Signaling in Postnatal Pituitary Expansion: Proliferation, Progenitors, and Cell Specification

    PubMed Central

    Nantie, Leah B.; Himes, Ashley D.; Getz, Dan R.

    2014-01-01

    Mutations in PROP1 account for up to half of the cases of combined pituitary hormone deficiency that result from known causes. Despite this, few signaling molecules and pathways that influence PROP1 expression have been identified. Notch signaling has been linked to Prop1 expression, but the developmental periods during which Notch signaling influences Prop1 and overall pituitary development remain unclear. To test the requirement for Notch signaling in establishing the normal pituitary hormone milieu, we generated mice with early embryonic conditional loss of Notch2 (conditional knockout) and examined the consequences of chemical Notch inhibition during early postnatal pituitary maturation. We show that loss of Notch2 has little influence on early embryonic pituitary proliferation but is crucial for postnatal progenitor maintenance and proliferation. In addition, we show that Notch signaling is necessary embryonically and postnatally for Prop1 expression and robust Pit1 lineage hormone cell expansion, as well as repression of the corticotrope lineage. Taken together, our studies identify temporal and cell type–specific roles for Notch signaling and highlight the importance of this pathway throughout pituitary development. PMID:24673559

  11. Trans-Agency Early-Life Exposures and Cancer Working Group

    Cancer.gov

    The Trans-Agency Early-Life Exposures and Cancer Working Group promotes integration of early-life events and exposures into public health cancer research, control, prevention, and policy strategies to reduce the cancer burden in the United States and globally.

  12. Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

    PubMed

    Trofimov, S S; Voronina, T A; Guzevatykh, L S

    2005-06-01

    We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

  13. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jusko, Todd A., E-mail: juskota@niehs.nih.gov; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA; De Roos, Anneclaire J.

    2010-05-15

    Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid weremore » assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.« less

  14. Multigenerational effects of bisphenol A or ethinyl estradiol exposure on F2 California mice (Peromyscus californicus) pup vocalizations

    PubMed Central

    Johnson, Sarah A.; Farrington, Michelle J.; Murphy, Claire R.; McAllister, Leif A.; Kaur, Sarabjit; Chun, Catherine; Ortega, Madison T.; Marshall, Brittney L.; Hoffmann, Frauke; Ellersieck, Mark R.; Schenk, A. Katrin

    2018-01-01

    Rodent pups use vocalizations to communicate with one or both parents in biparental species, such as California mice (Peromyscus californicus). Previous studies have shown California mice developmentally exposed to endocrine disrupting chemicals, bisphenol A (BPA) or ethinyl estradiol (EE), demonstrate later compromised parental behaviors. Reductions in F1 parental behaviors might also be due to decreased emissions of F2 pup vocalizations. Thus, vocalizations of F2 male and female California mice pups born to F1 parents developmentally exposed to BPA, EE, or controls were examined. Postnatal days (PND) 2–4 were considered early postnatal period, PND 7 and 14 were defined as mid-postnatal period, and PND 21 and 28 were classified as late postnatal period. EE pups showed increased latency to emit the first syllable compared to controls. BPA female pups had decreased syllable duration compared to control and EE female pups during the early postnatal period but enhanced responses compared to controls at late postnatal period; whereas, male BPA and EE pups showed greater syllable duration compared to controls during early postnatal period. In mid-postnatal period, F2 BPA and EE pups emitted greater number of phrases than F2 control pups. Results indicate aspects of vocalizations were disrupted in F2 pups born to F1 parents developmentally exposed to BPA or EE, but their responses were not always identical, suggesting BPA might not activate estrogen receptors to the same extent as EE. Changes in vocalization patterns by F2 pups may be due to multigenerational exposure to BPA or EE and/or reduced parental care received. PMID:29912934

  15. Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

    PubMed

    Wahle, P; Meyer, G

    1989-04-08

    The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of

  16. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    PubMed Central

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  17. In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice.

    PubMed

    Ramsey, Kathryn A; Larcombe, Alexander N; Sly, Peter D; Zosky, Graeme R

    2013-02-18

    Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100 μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations.

  18. In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

    PubMed Central

    2013-01-01

    Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

  19. Early Exposure to Intermediate-Frequency Magnetic Fields Alters Brain Biomarkers without Histopathological Changes in Adult Mice

    PubMed Central

    Win-Shwe, Tin-Tin; Ohtani, Shin; Ushiyama, Akira; Kunugita, Naoki

    2015-01-01

    Recently we have reported that intermediate-frequency magnetic field (IF-MF) exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT) for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1), inflammatory mediators (COX2, IL-1 β,TNF-α), and the oxidative stress marker heme-oxygenase (HO)-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes. PMID:25913185

  20. Influences of pre- and postnatal nutritional exposures on vascular/endocrine systems in animals.

    PubMed Central

    Hoet, J J; Ozanne, S; Reusens, B

    2000-01-01

    Human epidemiological and animal studies have revealed the long-term effects of malnutrition during gestation and early life on the health of the offspring. The aim of the current review is to survey the different means of achieving fetal malnutrition and its consequences, mainly in animals, and to identify key areas in which to direct future research. We address the impact of various models of a maternal protein-restricted diet and global maternal caloric restriction (either through the reduction of nutrient supply or through mechanic devices), the influence of maternal diabetes, and other maternal causes of fetal damage (maternal infections and toxic food components). More specifically, we enumerate data on how the different insults at different prenatal and early postnatal periods affect and program the development and the function of organs involved in diabetes, hypertension, and cardiovascular disease. Particular emphasis is given to the endocrine pancreas, but insulin-sensitive tissues, kidneys, and vasculature are also analyzed. Where available, the protective effects of maternal food supplementation for fetal organ development and function are discussed. Specific attention is paid to the amino acids profile, and the preventive role of taurine is discussed. Tentative indications about critical time windows for fetal development under different deleterious conditions are presented whenever possible. We also discuss future research and intervention. PMID:10852855

  1. Microglial disruption in young mice with early chronic lead exposure☆

    PubMed Central

    Sobin, Christina; Montoya, Mayra Gisel Flores; Parisi, Natali; Schaub, Tanner; Cervantes, Miguel; Armijos, Rodrigo X.

    2013-01-01

    The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31 μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals. PMID:23598043

  2. [Postnatal diagnosis of gastric volvulus revealing congenital diaphragmatic hernia].

    PubMed

    Aprahamian, A; Nouyrigat, V; Grévent, D; Hervieux, E; Chéron, G

    2017-05-01

    Postnatally diagnosed congenital diaphragmatic hernias (CDH) are rare and have a better prognosis than those diagnosed prenatally. Postnatal symptoms can be respiratory, digestive, or mixed. Gastric volvulus can reveal CDH. Symptoms are pain, abdominal distension, and/or vomiting. Upper gastrointestinal barium X-ray radiography provides the diagnosis. Prognosis is related to early surgical management in complicated forms with intestinal occlusion or sub-occlusion. We report on an infant who presented with vomiting, which revealed gastric volvulus associated with a CDH. Progression was favorable after surgical treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Prenatal chemical exposures and child language development.

    PubMed

    Dzwilewski, Kelsey L C; Schantz, Susan L

    2015-01-01

    The goal of this review is to summarize the evidence that prenatal and/or early postnatal exposure to certain chemicals, both manmade (insulating materials, flame retardants, pesticides) and naturally occurring (e.g., lead, mercury), may be associated with delays or impairments in language development. We focus primarily on a subset of more extensively studied chemicals-polychlorinated biphenyls (PCBs), lead, and methyl mercury-for which a reasonable body of literature on neurodevelopmental outcomes is available. We also briefly summarize the smaller body of evidence for other chemicals including polybrominated diphenyl ether flame retardants (PBDEs) and organophosphate pesticides. Very few studies have used specific assessments of language development and function. Therefore, we included discussion of aspects of cognitive development such as overall intellectual functioning and verbal abilities that rely on language, as well as aspects of cognition such as verbal and auditory working memory that are critical underpinnings of language development. A high percentage of prospective birth cohort studies of PCBs, lead, and mercury have reported exposure-related reductions in overall IQ and/or verbal IQ that persist into middle or late childhood. Given these findings, it is important that clinicians and researchers in communication sciences and disorders are aware of the potential for environmental chemicals to impact language development. The goal of this review is to summarize the evidence that prenatal and/or early postnatal exposure to certain chemicals may be associated with delays or impairments in language development. Readers will gain an understanding of the literature suggesting that early exposure to polychlorinated biphenyls (PCBs), lead, and mercury may be associated with decrements in cognitive domains that depend on language or are critical for language development. We also briefly summarize the smaller body of evidence regarding polybrominated diphenyl

  4. Pre- and postnatal exposure to intimate partner violence among South African HIV-infected mothers and infant developmental functioning at 12 months of age.

    PubMed

    Rodriguez, Violeta J; Peltzer, Karl; Matseke, Gladys; Weiss, Stephen M; Shine, Agnes; Jones, Deborah L

    2018-05-23

    In rural South Africa, pregnant HIV-infected women report high rates of psychological (55%) and physical (20%) intimate partner violence (IPV). IPV increases the risk of infant developmental delays. Such delays may have negative socioemotional and cognitive outcomes throughout the lifespan. This paper assesses the relationship between IPV and infant development in rural South Africa. The present investigation was a cross-sectional add-on follow-up designed retrospectively. A randomly selected sub-sample of mothers from the main randomized controlled trial (n = 72) were asked to participate with their infants at 12 months of age; all women invited agreed to participate. Women were 18.35 ± 5.47 weeks pregnant; demographics, HIV disclosure status, and pre- and postnatal IPV measured via the Conflict Tactics Scale during pregnancy at baseline and 12 months post-partum were assessed. Infant HIV serostatus and developmental functioning at 12 months of age were assessed. Women were a mean age of 29 ± 2 years. One third had completed at least 12 years of education and had a monthly income of ~ US$76. At 12 months post-partum, 6% of infants tested HIV seropositive. Postnatal physical IPV was associated with delays in cognitive and receptive language development p < 0.05, but only in unadjusted analyses. This study identified an association between early IPV exposure and infant cognitive and receptive communication delays. Given the small sample size, findings support replication. Longitudinal studies are needed to confirm temporal order and identify appropriate timing for interventions in HIV-exposed infants.

  5. Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors

    PubMed Central

    Soe, Ni Ni; Wen, Daniel J.; Poh, Joann S.; Li, Yue; Broekman, Birit F. P.; Chen, Helen; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D.; Meaney, Michael J.; Rifkin-Graboi, Anne; Qiu, Anqi

    2016-01-01

    This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children’s externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls. PMID:27073881

  6. Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Daunton, N. G.; Wade, C. E.

    2001-01-01

    A major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Recent spaceflight and centrifugation studies demonstrate that reproduction and ontogenesis in mammals are amenable to study under gravitational conditions that deviate considerably from those typically experienced on Earth (1 x g). In the present study, we tested the hypothesis that maternal reproductive experience determines neonatal outcome following gestation and birth under increased (hyper) gravity. Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g centrifugation from Gestational Day 11 either through birth or through the first postnatal week. On the day of birth, litter sizes were identical across gravity and parity conditions, although significantly fewer live neonates were observed among hypergravity-reared litters born to primigravid dams than among those born to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the hypergravity groups, neonatal mortality was comparable across parity conditions from Postnatal Day 1 through Day 7, at which time litter sizes stabilized. Maternal reproductive experience ameliorated neonatal losses during the first 24 h after birth but not on subsequent days, and neonatal mortality was associated with changes in maternal care patterns. These results indicate that repeated maternal reproductive experience affords protection against neonatal losses during exposure to increased gravity. Differential mortality of neonates born to primigravid versus bigravid dams denotes gravitational load as one environmental mechanism enabling the expression of parity-related variations in birth outcome.

  7. Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    De Long, Nicole E.; Barry, Eric J.; Pinelli, Christopher

    Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetinemore » exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty

  8. Association of outdoor air pollution and indoor renovation with early childhood ear infection in China.

    PubMed

    Deng, Qihong; Lu, Chan; Jiang, Wei; Zhao, Jinping; Deng, Linjing; Xiang, Yuguang

    2017-02-01

    Otitis media (OM) is a common infection in early childhood with repeated attacks that lead to long-term complications and sequelae, but its risk factors still remain unclear. To examine the risk of childhood OM for different indoor and outdoor air pollutants during different timing windows, with a purpose to identify critical windows of exposure and key components of air pollution in the development of OM. We conducted a retrospective cohort study of 1617 children aged 3-4 years in Changsha, China (2011-2012). Children's life-time prevalence of OM and exposure to indoor air pollution related to home renovation activities were surveyed by a questionnaire administered by the parents. Children's exposure to outdoor air pollution, including nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ), was estimated using the measured concentrations at municipal monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of childhood OM for prenatal and postnatal exposure to indoor and outdoor air pollution were examined by using logistic regression model. Life-time prevalence of OM in preschool children (7.3%) was associated not only with prenatal exposure to industrial air pollutant with adjusted OR (95% CI) = 1.44 (1.09-1.88) for a 27 μg/m 3 increase in SO 2 but also with postnatal exposure to indoor renovations with OR (95% CI) = 1.62 (1.05-2.49) for new furniture and 1.81 (1.12-2.91) for redecoration, particularly in girls. Combined exposure to outdoor SO 2 and indoor renovation significantly increased OM risk. Furthermore, we found that exposure to outdoor SO 2 and indoor renovation were significantly associated with the onset but not repeated attacks of OM. Prenatal exposure to outdoor industrial air pollution and postnatal exposure to indoor renovation are independently associated with early childhood OM in China and may cause the OM onset. Copyright © 2016 Elsevier Ltd. All

  9. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China

    PubMed Central

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-01-01

    Abstract The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84–8.92), 5.08 (95% CI: 1.12–8.41), 4.71 (95% CI: 1.78–7.66), 6.13 (95% CI: 2.83–9.44), and 5.81 (95% CI: 2.61–9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children. PMID:27495020

  10. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China.

    PubMed

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-08-01

    The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84-8.92), 5.08 (95% CI: 1.12-8.41), 4.71 (95% CI: 1.78-7.66), 6.13 (95% CI: 2.83-9.44), and 5.81 (95% CI: 2.61-9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children.

  11. Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice

    PubMed Central

    Bortolato, Marco; Godar, Sean C.; Tambaro, Simone; Li, Felix G.; Devoto, Paola; Coba, Marcelo P.; Chen, Kevin; Shih, Jean C.

    2013-01-01

    Monoamine oxidase (MAO) A, the major enzyme catalyzing the oxidative degradation of serotonin (5-hydroxytryptamine, 5-HT), plays a key role in emotional regulation. In humans and mice, MAO-A deficiency results in high 5-HT levels, antisocial, aggressive, and perseverative behaviors. We previously showed that the elevation in brain 5-HT levels in MAO-A knockout (KO) mice is particularly marked during the first two weeks of postnatal life. Building on this finding, we hypothesized that the reduction of 5-HT levels during these early stages may lead to enduring attenuations of the aggression and other behavioral aberrances observed in MAO-A KO mice. To test this possibility, MAO-A KO mice were treated with daily injections of a 5-HT synthesis blocker, the tryptophan hydroxylase inhibitor p-chloro-phenylalanine (pCPA, 300 mg/kg/day, IP), from postnatal day 1 through 7. As expected, this regimen significantly reduced 5-HT forebrain levels in MAO-A KO pups. These neurochemical changes persisted throughout adulthood, and resulted in significant reductions in marble-burying behavior, as well as increases in spontaneous alternations within a T-maze. Conversely, pCPA-treated MAO-A KO mice did not exhibit significant changes in anxiety-like behaviors in a novel open-field and elevated plus-maze; furthermore, this regimen did not modify their social deficits, aggressive behaviors and impairments in tactile sensitivity. Treatment with pCPA from postnatal day 8 through 14 elicited similar, yet milder, behavioral effects on marble-burying behavior. These results suggest that early developmental enhancements in 5-HT levels have long-term effects on the modulation of behavioral flexibility associated with MAO-A deficiency. PMID:23871843

  12. Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.

    PubMed

    Graham, Bronwyn M; Richardson, Rick

    2010-06-01

    Fibroblast growth factor-2 (FGF2) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute FGF2, administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering FGF2 on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to FGF2 affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of FGF2 on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of FGF2 (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to FGF2 increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to FGF2 did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate FGF2 as a critical signal involved in the development of learning and memory.

  13. Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

    PubMed

    Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

  14. Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dasari, Sameera; Yuan, Yukun, E-mail: yuanyuku@msu.ed

    2009-11-01

    Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 msmore » inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca{sup 2+}]{sub e} or application of the GABA{sub A} receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.« less

  15. Effects of Prenatal and Postnatal Parent Depressive Symptoms on Adopted Child HPA Regulation: Independent and Moderated Influences

    ERIC Educational Resources Information Center

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Harold, Gordon T.; Reiss, David

    2013-01-01

    This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck…

  16. Maternal nutrient restriction during late gestation and early postnatal growth in sheep differentially reset the control of energy metabolism in the gastric mucosa.

    PubMed

    Sebert, S P; Dellschaft, N S; Chan, L L Y; Street, H; Henry, M; Francois, C; Sharma, V; Fainberg, H P; Patel, N; Roda, J; Keisler, D; Budge, H; Symonds, M E

    2011-07-01

    Fetal growth restriction followed by accelerated postnatal growth contributes to impaired metabolic function in adulthood. The extent to which these outcomes may be mediated centrally within the hypothalamus, as opposed to in the periphery within the digestive tract, remains unknown. In a sheep model, we achieved intrauterine growth restriction experimentally by maternal nutrient restriction (R) that involved a 40% reduction in food intake through late gestation. R offspring were then either reared singly to accelerate postnatal growth (RA) or as twins and compared with controls also reared singly. From weaning, all offspring were maintained indoors until adulthood. A reduced litter size accelerated postnatal growth for only the first month of lactation. Independently from postnatal weight gain and later fat mass, R animals developed insulin resistance as adults. However, restricted accelerated offspring compared with both the control accelerated and restricted restricted offspring ate less and had higher fasting plasma leptin as adults, an adaptation which was accompanied by changes in energy sensing and cell proliferation within the abomasum. Additionally, although fetal restriction down-regulated gene expression of mammalian target of rapamycin and carnitine palmitoyltransferase 1-dependent pathways in the abomasum, RA offspring compensated for this by exhibiting greater activity of AMP-activated kinase-dependent pathways. This study demonstrates a role for perinatal nutrition in the peripheral control of food intake and in energy sensing in the gastric mucosal and emphasizes the importance of diet in early life in regulating energy metabolism during adulthood.

  17. Uptake and predictors of early postnatal follow–up care amongst mother–baby pairs in South Africa: Results from three population–based surveys, 2010–2013

    PubMed Central

    Larsen, Anna; Cheyip, Mireille; Aynalem, Getahun; Dinh, Thu–ha; Jackson, Debra; Ngandu, Nobubelo; Chirinda, Witness; Mogashoa, Mary; Kindra, Gupreet; Lombard, Carl; Goga, Ameena

    2017-01-01

    infant HIV exposure (exposed vs unexposed aOR = 1.2, 95% CI = 1.1–1.2) were the key factors associated with receiving recommended PNC visits. Conclusions Approximately 40% of neonates did not receive three or more postnatal care visits in the first 6 weeks of life from 2010–2013. To improve uptake of early PNC, early antenatal booking, more frequent antenatal care attendance, and attention to HIV negative women is needed. PMID:29302327

  18. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

    PubMed

    Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

    2017-05-01

    Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

  19. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

    PubMed Central

    Balaraman, Sridevi; Idrus, Nirelia M.; Miranda, Rajesh C.; Thomas, Jennifer D.

    2017-01-01

    Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol’s developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol’s long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4–9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4–21. On PD 22, subjects were sacrificed, and RNA isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was normalized with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p<0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p<0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

  20. Developmental programming: interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep

    PubMed Central

    Koneva, LA; Vyas, AK; McEachin, RC; Puttabyatappa, M; H-S, Wang; Sartor, MA; Padmanabhan, V

    2017-01-01

    Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85–141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. PMID:28079927

  1. Literature review. Outcomes associated with postnatal exposure to polychlorinated biphenyls (PCBs) via breast milk.

    PubMed

    Jorissen, Joanne

    2007-10-01

    Forty years ago manufacturers commonly used polychlorinated biphenyls (PCBs) in a wide variety of products. In the late 1970s, following research demonstrating neurotoxicity in animals, even at low levels, PCBs were banned internationally. Today PCBs are widespread environmental contaminants and may be isolated from breast milk of women worldwide. This article provides an overview of the current research on the relationship between PCBs in breast milk and their effects on breastfed children with regard to neurological effects, growth and maturity, potential mitigating effects of breastfeeding, and immunologic effects. The vast majority of results from this body of research indicate that despite higher PCB loads, breastfed children continue to fare better than their formula-fed peers. At this point, there is no evidence of a threshold among the general population beyond which the risks of breastfeeding outweigh the benefits, nor is there any evidence demonstrating a clinically significant negative effect of postnatal exposure to PCBs via breast milk. To date the majority of studies conclude that despite substantially higher PCB loads among breastfed infants, breastfeeding is still preferable to formula feeding.

  2. Postnatal treatment using curcumin supplements to amend the damage in VPA-induced rodent models of autism.

    PubMed

    Al-Askar, Maha; Bhat, Ramesa Shafi; Selim, Manar; Al-Ayadhi, Laila; El-Ansary, Afaf

    2017-05-10

    Valproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism. The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12.5th day of gestation. At 7 days from their birth, the animals were supplemented with a specific dose of curcumin. Forty neonatal male Western Albino rats were divided into four groups. Rats in group I received only phosphate-buffered saline, rats in group II were the prenatal VPA exposure newborns, rats in group III underwent prenatal VPA exposure supplemented with postnatal curcumin, and rats in group IV were given only postnatal curcumin supplements. VPA rats exhibited delayed maturation and lower body and brain weights with numerous signs of brain toxicity, such as depletion of IFN-γ, serotonin, glutamine, reduced glutathione, glutathione S-transferase, lipid peroxidase with an increase in CYP450, IL-6, glutamate, and oxidized glutathione. A curcumin supplement moderately corrected these dysfunctions and was especially noticeable in improving delayed maturation and abnormal weight. Curcumin plays a significant therapeutic role in attenuating brain damage that has been induced by prenatal VPA exposure in rats; however, its therapeutic role as a dietary supplement still must be certified for use in humans.

  3. Bone-specific gene expression patterns and whole bone tissue of female mice are programmed by early life exposure to soy isoflavones and folic acid.

    PubMed

    Kaludjerovic, Jovana; Ward, Wendy E

    2015-10-01

    Female mice exposed to soy isoflavones (ISO) during early postnatal life have improved bone outcomes at adulthood. Since long-lasting effects may be mediated by DNA methylation, we hypothesized that providing supplemental folic acid (FA), a methyl donor, during early life, would enhance the positive effect of ISO to bone health. Bone-specific gene expression patterns were studied to understand potential mechanisms. CD-1 dams (n=36) were randomized to adequate or supplemental levels of FA (2 or 8 mg/kg diet) during pregnancy and lactation, and offspring received corn oil or ISO (7 mg/kg body weight/d) from postnatal day 1 to 10. From weaning, pups were fed an adequate FA diet and were studied to 4 months of age. Female offspring exposed to supplemental FA+ISO had higher bone mineral density (BMD), trabecular connectivity and peak load at the lumbar spine compared to females exposed to adequate FA. Female offspring exposed to adequate FA+ISO or supplemental FA had higher (P<.05) BMD and greater resistance to fracture at the lumbar spine and the femur; higher trabecular connectivity at the lumbar spine; and lower expression of DNA methyltransferase 3a (Dnmt3a) and neuropeptide Y (NPY) in the femur compared to mice exposed to adequate FA. In addition, only mice exposed to adequate FA+ISO had microstructural improvements at the femur neck and higher serum osteoprotegrin (OPG) and insulin growth factor-I (IGF-I). In summary, exposure to supplemental FA did not enhance the positive effect of ISO in bone. However, exposure to adequate FA+ISO or supplemental FA improved bone at least in part by suppressing Dnmt3a and NPY. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Altered spatial learning and delay discounting in a rat model of human third trimester binge ethanol exposure

    PubMed Central

    Bañuelos, Cristina; Gilbert, Ryan J.; Montgomery, Karienn S.; Fincher, Annette S.; Wang, Haiying; Frye, Gerald D.; Setlow, Barry; Bizon, Jennifer L.

    2012-01-01

    Ethanol exposure during perinatal development can cause cognitive abnormalities including difficulties in learning, attention, and memory, as well as heightened impulsivity. The purpose of this study was to assess performance in spatial learning and impulsive choice tasks in rats subjected to an intragastric intubation model of binge ethanol exposure during human third trimester-equivalent brain development. Male and female Sprague–Dawley rat pups were intubated with ethanol (5.25 g/kg/day) on postnatal days 4–9. At adolescence (between postnatal days 35–38), these rats and sham intubated within-litter controls were trained in both spatial and cued versions of the Morris water maze. A subset of the male rats was subsequently tested on a delay-discounting task to assess impulsive choice. Ethanol-exposed rats were spatially impaired relative to controls, but performed comparably to controls on the cued version of the water maze. Ethanol-exposed rats also showed greater preference for large delayed rewards on the delay discounting task, but no evidence for altered reward sensitivity or perseverative behavior. These data demonstrate that early postnatal intermittent binge-like ethanol exposure has prolonged, detrimental, but selective effects on cognition, suggesting that even relatively brief ethanol exposure late in human pregnancy can be deleterious for cognitive function. PMID:22129556

  5. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    PubMed

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Developmental Programming: Postnatal Estradiol Modulation of Prenatally Organized Reproductive Neuroendocrine Function in Sheep

    PubMed Central

    Puttabyatappa, Muraly; Cardoso, Rodolfo C.; Herkimer, Carol; Veiga-Lopez, Almudena; Padmanabhan, Vasantha

    2016-01-01

    Gestational testosterone (T) excess, acting via both the androgenic and estrogenic pathways, advances puberty and disrupts the neuroendocrine estradiol (E) feedback and periovulatory hormonal dynamics in female sheep. These prenatally programmed defects may be subject to postnatal modifications by continued organizational and/or activational effects of steroids. The present study investigated 1) the organizational contribution of prenatal estrogen excess and 2) the impact of postnatal exposure to E in modulating the effects of prenatal androgen excess (T and dihydrotestosterone [DHT]) on puberty, neuroendocrine feedback mechanisms, and periovulatory hormonal dynamics in sheep. Pregnant Suffolk sheep were treated with T, DHT, E, or E plus DHT (ED) from days 30 to 90 of gestation. A subset of the control (C), T, and DHT female offspring received a constant-release E implant postnatally. Findings revealed that 1) prenatal E-treatment failed to reproduce the neuroendocrine disruptions predicted to be programmed by the estrogenic pathway and 2) prenatal ED-treatment did not adequately replicate the reproductive neuroendocrine defects induced by prenatal T excess. More importantly, continuous postnatal E-treatment, while delaying the onset of puberty and reducing the inhibitory effects of E on tonic luteinizing hormone (LH) release, failed to amplify the E positive feedback and periovulatory defects induced by prenatal T-treatment. Our results indicate that disruptions in E positive feedback mechanisms and periovulatory gonadotropin secretion induced by prenatal T-treatment are programmed predominantly during the prenatal life with postnatal exposure to E excess not contributing further to these disruptions. PMID:27222598

  7. Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism.

    PubMed

    Chen, Minjie; Liang, Shuai; Zhou, Huifen; Xu, Yanyi; Qin, Xiaobo; Hu, Ziying; Wang, Xiaoke; Qiu, Lianglin; Wang, Wanjun; Zhang, Yuhao; Ying, Zhekang

    2017-01-18

    Obesity is one of the leading threats to global public health. It is consequent to abnormal energy metabolism. Currently, it has been well established that maternal exposure to environmental stressors that cause inappropriate fetal development may have long-term adverse effects on offspring energy metabolism in an exposure timing-dependent manner, known as developmental programming of health and diseases paradigm. Rapidly increasing evidence has indicated that maternal exposure to ambient fine particles (PM 2.5 ) correlates to abnormal fetal development. In the present study, we therefore assessed whether maternal exposure to diesel exhaust PM 2.5 (DEP), the major component of ambient PM 2.5 in urban areas, programs offspring energy metabolism, and further examined how the timing of exposure impacts this programming. The growth trajectory of offspring shows that although prenatal maternal exposure to DEP did not impact the birth weight of offspring, it significantly decreased offspring body weight from postnatal week 2 until the end of observation. This weight loss effect of prenatal maternal exposure to DEP coincided with decreased food intake but not alteration in brown adipose tissue (BAT) morphology. The hypophagic effect of prenatal maternal exposure to DEP was in concord with decreased hypothalamic expression of an orexigenic peptide NPY, suggesting that the prenatal maternal exposure to DEP impacts offspring energy balance primarily through programming of food intake. Paradoxically, the reduced body weight resulted from prenatal maternal exposure to DEP was accompanied by increased mass of epididymal adipose tissue, which was due to hyperplasia as morphological analysis did not observe any hypertrophy. In direct contrast, the postnatal mothering by DEP-exposed dams increased offspring body weight during lactation and adulthood, paralleled by markedly increased fat accumulation and decreased UCP1 expression in BAT but not alteration in food intake. The weight

  8. Postnatal care in the community: report of an evaluation of birthing women's assessments of a postnatal home-care programme.

    PubMed

    Zadoroznyj, Maria

    2007-01-01

    For more than a decade, there has been a strong trend in many Western countries to decrease the length of time that women spend in hospital following childbirth. The research evidence regarding the consequences of early discharge for mothers and babies is mixed. Recent evidence has suggested that early discharge may not be randomly distributed across all sociodemographic groups of birthing women, and that the structures of home care have an important influence on maternal and child outcomes. In the context of decreasing lengths of hospital stay, the aim of the present study was to evaluate a new postnatal home support worker introduced into a geographically defined catchment area of a metropolitan hospital in South Australia. The evaluation included a formative process component to monitor recruitment strategies into the programme, as well as summative evaluation of a number of projected programme outcomes. The research methods used included interviews with antenatal women (n = 20) about their knowledge of and attitudes to the programme, and interviews with postnatal women (n = 63) about their transition home experience and assessment of the programme. Secondary analysis of client satisfaction surveys (n = 163) and aggregate breast-feeding data was also conducted. The results concur with previous research findings regarding the importance of rest and practical, home-based support in the postnatal period to maternal well-being, successful bonding and transition to motherhood. The results demonstrate the importance of well-structured home support services to maternal satisfaction and maternal well-being through the provision of physical, social and emotional care and support in the home.

  9. LACK OF EFFECT OF PERINATAL EXPOSURE TO A POLYBROMINATED DEPHENYL OTHER MIXTURE (DE-71) ON THE HABITUATION OF MOTOR ACTIVITY IN ADULT RATS.

    EPA Science Inventory

    Polybrominated diphenyl ethers (PBDEs) are used as flame retardants and are becoming increasingly evident in environmental media, wildlife and human breast milk. Published research in mice has shown that early postnatal exposure to some PBDEs attenuates the habituation of motor ...

  10. Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios.

    PubMed

    Tun, Hein M; Konya, Theodore; Takaro, Tim K; Brook, Jeffrey R; Chari, Radha; Field, Catherine J; Guttman, David S; Becker, Allan B; Mandhane, Piush J; Turvey, Stuart E; Subbarao, Padmaja; Sears, Malcolm R; Scott, James A; Kozyrskyj, Anita L

    2017-04-06

    Early-life exposure to household pets has the capacity to reduce risk for overweight and allergic disease, especially following caesarean delivery. Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health. To investigate the impact of pre- and postnatal pet exposure on infant gut microbiota following various birth scenarios, this study employed a large subsample of 746 infants from the Canadian Healthy Infant Longitudinal Development Study (CHILD) cohort, whose mothers were enrolled during pregnancy between 2009 and 2012. Participating mothers were asked to report on household pet ownership at recruitment during the second or third trimester and 3 months postpartum. Infant gut microbiota were profiled with 16S rRNA sequencing from faecal samples collected at the mean age of 3.3 months. Two categories of pet exposure (i) only during pregnancy and (ii) pre- and postnatally were compared to no pet exposure under different birth scenarios. Over half of studied infants were exposed to at least one furry pet in the prenatal and/or postnatal periods, of which 8% were exposed in pregnancy alone and 46.8% had exposure during both time periods. As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P < 0.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P < 0.001, FDRp = 0.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods. All of these associations were independent of maternal

  11. Sulforaphane attenuates postnatal proteasome inhibition and improves spatial learning in adult mice.

    PubMed

    Sunkaria, Aditya; Bhardwaj, Supriya; Yadav, Aarti; Halder, Avishek; Sandhir, Rajat

    2018-01-01

    Proteasomes are known to degrade proteins involved in various processes like metabolism, signal transduction, cell-cycle regulation, inflammation, and apoptosis. Evidence showed that protein degradation has a strong influence on developing neurons as well as synaptic plasticity. Here, we have shown that sulforaphane (SFN) could prevent the deleterious effects of postnatal proteasomal inhibition on spatial reference and working memory of adult mice. One day old Balb/c mice received intracerebroventricular injections of MG132 and SFN. Sham received an equal volume of aCSF. We observed that SFN pre-administration could attenuate MG132 mediated decrease in proteasome and calpain activities. In vitro findings revealed that SFN could induce proteasomal activity by enhancing the expression of catalytic subunit-β5. SFN pre-administration prevented the hippocampus based spatial memory impairments during adulthood, mediated by postnatal MG132 exposure. Histological examination showed deleterious effects of MG132 on pyramidal neurons and granule cell neurons in DG and CA3 sub-regions respectively. Furthermore, SFN pre-administration has shown to attenuate the effect of MG132 on proteasome subunit-β5 expression and also induce the Nrf2 nuclear translocation. In addition, SFN pre-administered mice have also shown to induce expression of pCaMKII, pCreb, and mature/pro-Bdnf, molecules which play a crucial role in spatial learning and memory consolidation. Our findings have shown that proteasomes play an important role in hippocampal synaptic plasticity during the early postnatal period and SFN pre-administration could enhance the proteasomal activity as well as improve spatial learning and memory consolidation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Prenatal exposure to chromium induces early reproductive senescence by increasing germ cell apoptosis and advancing germ cell cyst breakdown in the F1 offspring.

    PubMed

    Sivakumar, Kirthiram K; Stanley, Jone A; Arosh, Joe A; Pepling, Melissa E; Burghardt, Robert C; Banu, Sakhila K

    2014-04-01

    Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world's leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25 ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27-Bax-caspase-3 proteins and by increasing p53-SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny. Published by Elsevier Inc.

  13. Prenatal exposure to chromium induces early reproductive senescence by increasing germ cell apoptosis and advancing germ cell cyst breakdown in the F1 offspring

    PubMed Central

    Sivakumar, Kirthiram K.; Stanley, Jone A.; Arosh, Joe A.; Pepling, Melissa E.; Burghardt, Robert C.; Banu, Sakhila K.

    2014-01-01

    Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world’s leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25 ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27–Bax–caspase-3 proteins and by increasing p53–SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny. PMID:24530425

  14. First-time fathers' postnatal experiences and support needs: A descriptive qualitative study.

    PubMed

    Shorey, Shefaly; Dennis, Cindy-Lee; Bridge, Shiho; Chong, Yap Seng; Holroyd, Eleanor; He, Hong-Gu

    2017-12-01

    To explore first-time fathers' postnatal experiences and support needs in the early postpartum period. The postnatal period is a stressful transition period for new fathers. It is imperative to understand their needs and experiences to provide appropriate support for them. The majority of previous studies were based in Western countries and explored fathers' needs during pregnancy and childbirth, with few studies conducted in the postnatal period. In Singapore, a multiracial society with differing paternal cultural values from its Western counterparts, there is considerable need to examine the experiences and needs of first-time fathers. A descriptive qualitative design was used. Data were collected from November 2015-January 2016. Fifteen first-time fathers were recruited from two postnatal wards of a public hospital, using a purposive sampling method. A semi-structured interview guide was used to conduct face-to-face interviews. A thematic analysis was conducted and ethics approval was sought for this study. Four overarching themes and seventeen subthemes were generated. The four overarching themes were: (1) No sense of reality to sense of responsibility; (2) Unprepared and challenged; (3) Support: needs, sources, experience and attitude; and (4) Future help for fathers. Fathers undergo a transition phase where they have unmet support needs during the early postnatal period. Understanding and addressing these needs may facilitate smooth transition to fatherhood. This study's findings can be used to involve fathers and design future supportive educational programs to promote positive parenting experiences and family dynamics. © 2017 John Wiley & Sons Ltd.

  15. Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

    PubMed Central

    Gong, Linji; Ma, Yuanyuan; Xu, Haiwei; Gu, Zhanjun; Zhu, Jingci; Fan, Xiaotang

    2018-01-01

    Introduction Silica nanoparticles (SiO2-NPs) are currently among the most widely used nanomaterials, but their potentially adverse effects on brain development remain unknown. The developing brain is extremely sensitive to NP neurotoxicity during the early postnatal period. Materials and methods Herein, we investigated the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3, respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor proliferation at P8 and long-term neurobehavior in adults. Results SiO2-NP exposure resulted in inflammatory cell infiltration in lung tissue, microglia over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal precursor proliferation in the DG-subgranular zone at P8. Moreover, after exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and slight anxiety-like behaviors in adulthood, but this exposure did not induce locomotor activity impairment, depression-like behavior, or short-term memory impairment. Discussion These findings suggest that early-age SiO2-NP exposure induced inflammation and inhibited precursor proliferation in the DG in a dose-dependent manner, which might be related to the social dysfunction observed in adulthood.

  16. Parsing the Effects Violence Exposure in Early Childhood: Modeling Developmental Pathways

    PubMed Central

    Carter, Alice S.; Ford, Julian D.

    2012-01-01

    Objective To prospectively examine pathways from early childhood violence exposure and trauma-related symptoms to school-age emotional health. Methods A longitudinal, birth cohort (N = 437) was assessed with parent reports of lifetime violence exposure and trauma-related symptoms at 3 years of age and later, internalizing and externalizing symptoms, and social competence at school age. Results Early family and neighborhood violence correlated significantly with early trauma-related symptoms and also significantly predicted school-age internalizing and externalizing symptoms and poorer competence, independent of sociodemographic risk and past-year violence exposure. Longitudinal pathways were significantly mediated by arousal and avoidance symptoms at 3 years of age, which increased risk for clinically significant emotional problems and lower competence at school age (adjusted odds ratios = 3.1–6.1, p < 0.01). Conclusions Trauma-related symptoms may mediate developmental pathways from early violence exposure to later emotional health. Interventions that prevent or reduce early trauma-related symptoms may ameliorate the long-term deleterious impact of violence exposure. PMID:21903730

  17. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits

    PubMed Central

    Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

    2016-01-01

    Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

  18. Prevalence and risk factors for postnatal depression in Sabah, Malaysia: a cohort study.

    PubMed

    Mohamad Yusuff, Aza Sherin; Tang, Li; Binns, Colin W; Lee, Andy H

    2015-03-01

    Postnatal depression can have serious consequences for both the mother and infant. However, epidemiological data required to implement appropriate early prevention are still lacking in Malaysia. To investigate the prevalence of postnatal depression within six months postpartum and associated risk factors among women in Sabah, Malaysia. A prospective cohort study of 2072 women was conducted in Sabah during 2009-2010. Participants were recruited at 36-38 weeks of gestation and followed up at 1, 3 and 6 months postpartum. The presence of depressive symptoms was assessed using the validated Malay version of the Edinburgh Postnatal Depression Scale. Logistic regression analyses were performed to ascertain risk factors associated with postnatal depression. Overall, 14.3% of mothers (95% confidence interval (CI) 12.5-16.2%) had experienced depression within the first six months postpartum. Women depressed during pregnancy (odds ratio (OR) 3.71, 95% CI 2.46-5.60) and those with consistent worries about the newborn (OR 1.68, 95% CI 1.16-2.42) were more likely to suffer from depression after childbirth. Women whose husband assisted with infant care (OR 0.43, 95% CI 0.20-0.97) and mothers who were satisfied with their marital relationship (OR 0.27, 95% CI 0.09-0.81) appeared to incur a reduced risk of postnatal depression. A substantial proportion of mothers suffered from postnatal depression in Sabah, Malaysia. Screening and intervention programmes targeting vulnerable subgroups of women during antenatal and early postpartum periods are recommended to deal with the problem. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  19. PERSPECTIVES ON THE CONCERN FOR AND MANAGEMENT OF PRENATAL CHEMICAL EXPOSURE AND POSTNATAL EFFECTS

    EPA Science Inventory

    This paper was presented as the introduction to a session on the history and epidemiology of prenatal chemical exposure. lthough teratology and developmental toxicology had its experimental beginnings in the early part of this century, the potential for human developmental toxici...

  20. Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep.

    PubMed

    Koneva, L A; Vyas, A K; McEachin, R C; Puttabyatappa, M; Wang, H-S; Sartor, M A; Padmanabhan, V

    2017-01-01

    Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22-59.

    PubMed

    Türedi, Sibel; Kerimoğlu, Gökçen; Mercantepe, Tolga; Odacı, Ersan

    2017-09-01

    To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22-59, inclusive. Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1 h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values. The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004, respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004, respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM. We conclude that continuous exposure to the effect of 900-MHz EMF for 1 h a day on postnatal days 22-59, inclusive, causes an

  2. Preservation of chromosomal integrity in murine spermatozoa derived from gonocytes and spermatogonial stem cells surviving prenatal and postnatal exposure to γ-rays in mice.

    PubMed

    Watanabe, Hiroyuki; Kohda, Atsushi; Komura, Jun-Ichiro; Tateno, Hiroyuki

    2017-07-01

    Pre- and postnatal male mice were acutely (659-690 mGy/min) and continuously (0.303 mGy/min) exposed to 2 Gy γ-rays to evaluate spermatogenic potential and chromosome damage in their germ cells as adults. Acute irradiation on Days 15.5, 16.5, and 17.5 post-coitus affected testicular development, as a result of massive quiescent gonocyte loss; the majority of the seminiferous tubules in these testes were devoid of germ cells. Acute irradiation on Days 18.5 and 19.5 post-coitus had less effect on testicular development and spermatogenesis, even though germ cells were quiescent gonocytes on these days. Adverse effects on testicular development and spermatogenesis were observed following continuous irradiation between Days 14.5 and 19.5 post-coitus. Exposure to acute and continuous postnatal irradiation after the differentiation of spermatogonial stem cells and spermatogonia resulted in nearly all of the seminiferous tubules exhibiting spermatogenesis. Neither acute nor continuous irradiation was responsible for the increased number of multivalent chromosomes in primary-spermatocyte descendents of the exposed gonocytes. In contrast, a significant increase in cells with multivalent chromosomes was observed following acute irradiation on Days 4 and 11 post-partum. No significant increases in unstable structural chromosomal aberrations or aneuploidy in spermatozoa were observed, regardless of cell stage at irradiation or the radiation dose-rate. Thus, murine germ cells that survive prenatal and postnatal irradiation can restore spermatogenesis and produce viable spermatozoa without chromosome damage. These findings may provide a better understanding of reproductive potential following accidental, environmental, or therapeutic irradiation during the prenatal and postnatal periods in humans. © 2017 Wiley Periodicals, Inc.

  3. The human early-life exposome (HELIX): project rationale and design.

    PubMed

    Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

    2014-06-01

    Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

  4. Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep.

    PubMed

    Puttabyatappa, Muraly; Cardoso, Rodolfo C; Herkimer, Carol; Veiga-Lopez, Almudena; Padmanabhan, Vasantha

    2016-08-01

    Gestational testosterone (TS) excess, acting via both the androgenic and estrogenic pathways, advances puberty and disrupts the neuroendocrine estradiol (E2) feedback and periovulatory hormonal dynamics in female sheep. These prenatally programmed defects may be subject to postnatal modifications by continued organizational and/or activational effects of steroids. This study investigated (1) the organizational contribution of prenatal estrogen excess and (2) the impact of postnatal exposure to E2 in modulating the effects of prenatal androgen excess (TS and dihydrotestosterone (DHT)) on puberty, neuroendocrine feedback mechanisms, and periovulatory hormonal dynamics in sheep. Pregnant Suffolk sheep were treated with TS, DHT, E2, or E2 plus DHT (ED) from days 30 to 90 of gestation. A subset of the control (C), TS, and DHT female offspring received a constant-release E2 implant postnatally. Findings revealed that (1) prenatal E2-treatment failed to reproduce the neuroendocrine disruptions predicted to be programmed by the estrogenic pathway and (2) prenatal E2D-treatment did not adequately replicate the reproductive neuroendocrine defects induced by prenatal TS excess. More importantly, continuous postnatal E2-treatment, while delaying the onset of puberty and reducing the inhibitory effects of E2 on tonic luteinizing hormone (LH) release, failed to amplify the E2-positive feedback and periovulatory defects induced by prenatal TS-treatment. Our results indicate that disruptions in E2-positive feedback mechanisms and periovulatory gonadotropin secretion induced by prenatal TS-treatment are programmed predominantly during the prenatal life with postnatal exposure to E2 excess not contributing further to these disruptions. © 2016 Society for Reproduction and Fertility.

  5. Association between maternal depressive symptoms in the early post-natal period and responsiveness in feeding at child age 2 years.

    PubMed

    Mallan, Kimberley M; Daniels, Lynne A; Wilson, Jacinda L; Jansen, Elena; Nicholson, Jan M

    2015-10-01

    Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04-0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001-0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005-0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01-0.29, P = 0.03) feeding practices (ΔR(2) values: 0.02-0.03, P < 0.05). This study provides evidence for the proposed link between maternal post-natal depressive symptoms and lower responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship. © 2014 John Wiley & Sons Ltd.

  6. Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors.

    PubMed

    Wen, Hui-Ju; Chiang, Tung-Liang; Lin, Shio-Jean; Guo, Yue Leon

    2015-05-01

    Symptoms of atopic disease start early in human life. Predicting risk for childhood asthma by early-life exposure would contribute to disease prevention. A birth cohort study was conducted to investigate early-life risk factors for childhood asthma and to develop a predictive model for the development of asthma. National representative samples of newborn babies were obtained by multistage stratified systematic sampling from the 2005 Taiwan Birth Registry. Information on potential risk factors and children's health was collected by home interview when babies were 6 months old and 5 yr old, respectively. Backward stepwise regression analysis was used to identify the risk factors of childhood asthma for predictive models that were used to calculate the probability of childhood asthma. A total of 19,192 children completed the study satisfactorily. Physician-diagnosed asthma was reported in 6.6% of 5-yr-old children. Pre-pregnancy factors (parental atopy and socioeconomic status), perinatal factors (place of residence, exposure to indoor mold and painting/renovations during pregnancy), and postnatal factors (maternal postpartum depression and the presence of atopic dermatitis before 6 months of age) were chosen for the predictive models, and the highest predicted probability of asthma in 5-yr-old children was 68.1% in boys and 78.1% in girls; the lowest probability in boys and girls was 4.1% and 3.2%, respectively. This investigation provides a technique for predicting risk of childhood asthma that can be used to developing a preventive strategy against asthma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Attitudes and adjustment to the parental role in mothers following treatment for postnatal depression.

    PubMed

    Wan, Ming Wai; Sharp, Deborah J; Howard, Louise M; Abel, Kathryn M

    2011-06-01

    Few intervention studies of postnatal depression (PND) have evaluated accompanying changes in parenting, in spite of mounting evidence that exposure to chronic depression is detrimental to infant development. This study examined maternal attitudes and adjustment over the first postnatal year within a treatment trial. The aim was to examine whether maternal adjustment improved with earlier remission, and with combined medical and psychological treatment. As part of a multicentre pragmatic randomised controlled trial of treatment for PND, mothers completed a measure of maternal adjustment and attitudes and the Edinburgh Postnatal Depression Scale at an initial home visit (week 0) and three follow-ups (weeks 4, 18 and 44). Maternal attitudes and adjustment improved with PND remission; earlier remission conferred no additional benefit by 44-week follow-up. In line with previous studies, no particular treatment modality (antidepressant or health-visitor delivered non-directive counselling), or combination of treatments, was more effective for improving adjustment to parenthood. However, the earlier start of antidepressant treatment provided a short-term advantage for improving attitudes and reducing perceived stress. As a result of the study's pragmatic trial design, there was high treatment non-compliance and no 'pure' control group. More depressed mothers may have been less likely to complete the maternal adjustment and attitudes measure. Effective treatment of PND is important not only for the mother's wellbeing but also for healthy adjustment to parenthood. Provision of treatment choice and early antidepressant treatment are suggested for optimising maternal attitudes and adjustment. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Early life allergen and air pollutant exposures alter longitudinal blood immune profiles in infant rhesus monkeys.

    PubMed

    Crowley, Candace M; Fontaine, Justin H; Gerriets, Joan E; Schelegle, Edward S; Hyde, Dallas M; Miller, Lisa A

    2017-08-01

    Early life is a critical period for the progressive establishment of immunity in response to environmental stimuli; the impact of airborne challenges on this process is not well defined. In a longitudinal fashion, we determined the effect of episodic house dust mite (HDM) aerosol and ozone inhalation, both separately and combined, on peripheral blood immune cell phenotypes and cytokine expression from 4 to 25weeks of age in an infant rhesus monkey model of childhood development. Immune profiles in peripheral blood were compared with lung lavage at 25weeks of age. Independent of exposure, peripheral blood cell counts fluctuated with chronologic age of animals, while IFNγ and IL-4 mRNA levels increased over time in a linear fashion. At 12weeks of age, total WBC, lymphocyte numbers, FoxP3 mRNA and IL-12 mRNA were dramatically reduced relative to earlier time points, but increased to a steady state with age. Exposure effects were observed for monocyte numbers, as well as CCR3, FoxP3, and IL-12 mRNA levels in peripheral blood. Significant differences in cell surface marker and cytokine expression were detected following in vitro HDM or PMA/ionomycin stimulation of PBMC isolated from animals exposed to either HDM or ozone. Lavage revealed a mixed immune phenotype of FoxP3, IFNγ and eosinophilia in association with combined HDM plus ozone exposure, which was not observed in blood. Collectively, our findings show that airborne challenges during postnatal development elicit measureable cell and cytokine changes in peripheral blood over time, but exposure-induced immune profiles are not mirrored in the lung. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Maternal postnatal mental health and later emotional-behavioural development of children: the mediating role of parenting behaviour.

    PubMed

    Giallo, R; Cooklin, A; Wade, C; D'Esposito, F; Nicholson, J M

    2014-05-01

    Maternal postnatal mental health difficulties have been associated with poor outcomes for children. One mechanism by which parent mental health can impact on children's outcomes is via its effects on parenting behaviour. The longitudinal relationships between maternal postnatal distress, parenting warmth, hostility and child well-being at age seven were examined for 2200 families participating in a population-based longitudinal study of Australian children. The relationship between postnatal distress and children's later emotional-behavioural development was mediated by parenting hostility, but not parenting warmth, even after accounting for concurrent maternal mental health. Postnatal distress was more strongly associated with lower parenting warmth for mothers without a past history of depression compared with mothers with a past history of depression. These findings underscore the contribution of early maternal well-being to later parenting and child outcomes, highlighting the importance of mental health and parenting support in the early parenting years. Implications for policy and practice are discussed. © 2013 John Wiley & Sons Ltd.

  10. Prenatal hydronephrosis: postnatal evaluation and management.

    PubMed

    Vemulakonda, Vijaya; Yiee, Jenny; Wilcox, Duncan T

    2014-08-01

    Congenital hydronephrosis is one of the most common anomalies identified on antenatal ultrasound. The underlying etiology of congenital hydronephrosis is multifold, ranging from transient hydronephrosis in utero to clinically significant congenital anomalies of the kidney and urinary tract. While traditional management of hydronephrosis was aimed at relieving symptoms, the advent of routine prenatal ultrasound has led to a shift in the goal of treatment to prevention of renal injury in the asymptomatic patient. However, despite this focus on renal preservation, the diagnostic criteria for identification of children "at risk" for renal damage that can be alleviated by surgical treatment remain a subject of debate. Both antenatal and postnatal imaging studies have been evaluated as indicators for potential reversible renal damage and have been used as potential indicators of the need for surgical intervention. The aim of this review is to discuss the current literature regarding the role of postnatal clinical and radiographic evaluation to identify children who may benefit from early surgical intervention.

  11. Retinotopic Distribution of Structural and Functional Damages following Bright Light Exposure of Juvenile Rats

    PubMed Central

    Polosa, Anna; Liu, Wenwen; Lachapelle, Pierre

    2016-01-01

    In the present study, we aimed at better understanding the short (acute) and long term (chronic) degenerative processes characterizing the juvenile rat model of light-induced retinopathy. Electroretinograms, visual evoked potentials (VEP), retinal histology and western blots were obtained from juvenile albino Sprague-Dawley rats at preselected postnatal ages (from P30 to P400) following exposure to 10,000 lux from P14 to P28. Our results show that while immediately following the cessation of exposure, photoreceptor degeneration was concentrated within a well delineated area of the superior retina (i.e. the photoreceptor hole), with time, this hole continued to expand to form an almost photoreceptor-free region covering most of superior-inferior axis. By the end of the first year of life, only few photoreceptors remained in the far periphery of the superior hemiretina. Interestingly, despite a significant impairment of the outer retinal function, the retinal output (VEP) was maintained in the early phase of this retinopathy. Our findings thus suggest that postnatal exposure to a bright luminous environment triggers a degenerative process that continues to impair the retinal structure and function (mostly at the photoreceptor level) long after the cessation of the exposure regimen (more than 1 year documented herein). Given the slow degenerative process triggered following postnatal bright light exposure, we believe that our model represents an attractive alternative (to other more genetic models) to study the pathophysiology of photoreceptor-induced retinal degeneration as well as therapeutic strategies to counteract it. PMID:26784954

  12. Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring.

    PubMed

    Grote, Konstanze; Hobler, Carolin; Andrade, Anderson J M; Grande, Simone Wichert; Gericke, Christine; Talsness, Chris E; Appel, Klaus E; Chahoud, Ibrahim

    2007-09-05

    The organotin compound (OTC) triphenyltin (TPT) is used extensively as a herbicide, pesticide and fungicide in agriculture as well as, together with tributyltin (TBT), in marine antifouling paints. We studied the effects of in utero exposure to 2 or 6 mg triphenyltinchloride (TPTCl)/kgb.w. on pregnancy outcome and postnatal development in rat offspring. Gravid Wistar rats were treated per gavage from gestational day 6 until the end of lactation. In the 6 mg TPTCl dose group gestational mortality in dams as well as an increased incidence of anticipated and delayed parturition was observed. Furthermore, treatment resulted in a significant increase in perinatal mortality, a decrease in lactational body weight gain as well as in delayed physical maturation of offspring. Similarily, exposure to 2mg TPTCl/kgb.w. resulted in a significant increase in perinatal mortality and in delayed eye opening. Lactational body weight gain and other landmarks of physical maturation were unaffected in the low dose group. We conclude, that in utero exposure to TPTCl at the described dose levels severely affected pregnancy outcome and perinatal survival of offspring. These results were unexpected, as in two earlier studies with pubertal rats TPTCl at the same dose levels no signs of general toxicity were observed.

  13. Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

    PubMed

    Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

    2016-09-15

    Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Early and Later Life Stress Alter Brain Activity and Sleep in Rats

    PubMed Central

    Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2013-01-01

    Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

  15. The die is cast - Arsenic exposure in early life and disease susceptibility

    EPA Science Inventory

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  16. Update on Early Nutrition and Food Allergy in Children.

    PubMed

    Lee, Sun Eun; Kim, Hyeyoung

    2016-05-01

    With growing evidence of an increase in the prevalence, food allergy has been emerged as a new public health problem. As treatment and management of food allergy remain challenging, more attention has been paid to the importance of prevention of food allergy. Although the exact mechanism of recent epidemic is not fully understood, it is suggested that nutritional exposure in early life may play an important role in food allergy development. The underlying hypothesis is that nutritional status or food exposure in the critical period of fetal development can affect the programming of immune system and modify the risk of immunologic reactions to foods in postnatal life. We review accumulating epidemiological studies to examine an association between nutritional exposure during pregnancy or early infancy and food allergy development in children. We also discuss recent advances in the studies of the genetic and epigenetic regulation of food allergy and evaluate the role of early nutrition in food allergy development to provide a new perspective on the prevention of food allergy.

  17. Increased anxiety-related behavior in male and female adult rats following early and late adolescent exposure to 3,4-methylenedioxymethamphetamine (MDMA).

    PubMed

    Kolyaduke, Olga V; Hughes, Robert N

    2013-02-01

    Subsequent behavioral effects in adulthood of daily exposure to MDMA during early or late adolescence were assessed in both male and female rats. From either postnatal day (PND) 35 (early adolescence) or PND45 (late adolescence), PVG/c rats of each sex were exposed via intraperitoneal injections to saline or 10mg/kg MDMA for 10 consecutive days. They were regularly weighed during treatment and again on PND90. At this age, their anxiety-related behavior was determined from frequencies of ambulation, rearing, grooming, defecation and occupancy of the center and corners of an open field, as well as entries into and time spent in the light compartment of a light-dark box. Spatial and working memories were assessed by preferences for a novel Y-maze arm, and by recognition of a novel object. MDMA-exposed rats gained less weight during treatment than saline controls but were heavier on PND90 depending on their sex or age when treated. As shown by decreased open-field ambulation (for males only) and increased defecation plus fewer entries into the light compartment of the light-dark box and entries into both arms of a Y maze, MDMA exposure increased adult anxiety-related behavior particularly for rats treated during late adolescence. There was no evidence of any effects on either spatial or working memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Early Exposure to General Anesthesia Disrupts Spatial Organization of Presynaptic Vesicles in Nerve Terminals of the Developing Rat Subiculum.

    PubMed

    Lunardi, N; Oklopcic, A; Prillaman, M; Erisir, A; Jevtovic-Todorovic, V

    2015-10-01

    Exposure to general anesthesia (GA) during critical stages of brain development induces widespread neuronal apoptosis and causes long-lasting behavioral deficits in numerous animal species. Although several studies have focused on the morphological fate of neurons dying acutely by GA-induced developmental neuroapoptosis, the effects of an early exposure to GA on the surviving synapses remain unclear. The aim of this study is to study whether exposure to GA disrupts the fine regulation of the dynamic spatial organization and trafficking of synaptic vesicles in presynaptic terminals. We exposed postnatal day 7 (PND7) rat pups to a clinically relevant anesthetic combination of midazolam, nitrous oxide, and isoflurane and performed a detailed ultrastructural analysis of the synaptic vesicle architecture at presynaptic terminals in the subiculum of rats at PND 12. In addition to a significant decrease in the density of presynaptic vesicles, we observed a reduction of docked vesicles, as well as a reduction of vesicles located within 100 nm from the active zone, in animals 5 days after an initial exposure to GA. We also found that the synaptic vesicles of animals exposed to GA are located more distally with respect to the plasma membrane than those of sham control animals and that the distance between presynaptic vesicles is increased in GA-exposed animals compared to sham controls. We report that exposure of immature rats to GA during critical stages of brain development causes significant disruption of the strategic topography of presynaptic vesicles within the nerve terminals of the subiculum.

  19. Early Sign Language Exposure and Cochlear Implantation Benefits.

    PubMed

    Geers, Ann E; Mitchell, Christine M; Warner-Czyz, Andrea; Wang, Nae-Yuh; Eisenberg, Laurie S

    2017-07-01

    Most children with hearing loss who receive cochlear implants (CI) learn spoken language, and parents must choose early on whether to use sign language to accompany speech at home. We address whether parents' use of sign language before and after CI positively influences auditory-only speech recognition, speech intelligibility, spoken language, and reading outcomes. Three groups of children with CIs from a nationwide database who differed in the duration of early sign language exposure provided in their homes were compared in their progress through elementary grades. The groups did not differ in demographic, auditory, or linguistic characteristics before implantation. Children without early sign language exposure achieved better speech recognition skills over the first 3 years postimplant and exhibited a statistically significant advantage in spoken language and reading near the end of elementary grades over children exposed to sign language. Over 70% of children without sign language exposure achieved age-appropriate spoken language compared with only 39% of those exposed for 3 or more years. Early speech perception predicted speech intelligibility in middle elementary grades. Children without sign language exposure produced speech that was more intelligible (mean = 70%) than those exposed to sign language (mean = 51%). This study provides the most compelling support yet available in CI literature for the benefits of spoken language input for promoting verbal development in children implanted by 3 years of age. Contrary to earlier published assertions, there was no advantage to parents' use of sign language either before or after CI. Copyright © 2017 by the American Academy of Pediatrics.

  20. Burden of higher lead exposure in African-Americans starts in utero and persists into childhood.

    PubMed

    Cassidy-Bushrow, Andrea E; Sitarik, Alexandra R; Havstad, Suzanne; Park, Sung Kyun; Bielak, Lawrence F; Austin, Christine; Johnson, Christine Cole; Arora, Manish

    2017-11-01

    Recent public health lead crises in urban areas emphasize the need to better understand exposure to environmental toxicants, particularly in higher risk groups. Although African-American children have the highest prevalence of elevated blood lead levels in the United States, little is known about when this trajectory of disproportionate burden of lead exposure first emerges. Using tooth-matrix biomarkers that directly measure fetal and early childhood metal levels, the primary goal of this study was to determine if there were racial disparities in lead levels during fetal development and early childhood. Manganese, an essential nutrient that modifies the neurotoxic effects of lead, was also measured. Pregnant women served by the Henry Ford Health System and living in a predefined geographic area in and around Detroit, Michigan, were recruited during the second trimester or later into the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a population-based birth cohort. Offspring born between September 2003 and December 2007 were studied in childhood. Child race was parent-reported. Lead and manganese during the second and third trimesters, early postnatal life (birth through age 1year) and early childhood (age 1 through time of tooth shedding, which ranges from 6 to 12years) were measured via high-resolution microspatial mapping of dentin growth rings, a validated biomarker for prenatal and childhood metal exposure. African-American children (N=71) had 2.2 times higher lead levels in the second and third trimesters (both p<0.001) and 1.9 times higher lead levels postnatally in the first year of life (p=0.003) compared to white children (N=51). Lead levels in African-American children were also higher during childhood, but this effect was only marginally significant (p=0.066) and was attenuated after covariate adjustment. Additionally, we observed that African-American children had lower tooth‑manganese levels during the third

  1. Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P.

    PubMed

    Shvarev, Y N; Lagercrantz, H

    2006-10-01

    Developmental changes in the respiratory activity and its modulation by substance P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from the day of birth to day 3 (P0-P3). The respiratory network activity in the ventrolateral medulla was represented by two types of bursts: basic regular bursts with typical decrementing shape and biphasic bursts appearing after augmented biphasic discharges in inspiratory neurons. With advancing postnatal age the respiratory output was considerably modified; the basic rhythm became faster by 20%, whereas the biphasic burst rate, which was originally 15 times slower, declined further by 180% and the C4 burst duration significantly decreased by 20% due to reduced decay time without preceding changes in the central inspiratory drive. SP had an age-dependent excitatory effect on respiratory activity. In the basic rhythm, SP could induce transient rhythm cessations on P0-P2 but not on P3. For the biphasic burst frequency, the sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP-induced changes increased. In both types of bursts, SP prolonged C4 burst duration due to increasing decay time. This effect was three times greater on P3 and did not depend on the central inspiratory drive. Our results suggest that the potency of SP to regulate the respiratory activity elevates during the early postnatal period. The developmental changes in the respiratory activity appear to represent the transient stage in the maturation of rhythm and pattern generation mechanisms facilitating adaptive behavior of a quickly growing organism.

  2. Effects of adolescent methamphetamine and nicotine exposure on behavioral performance and MAP-2 immunoreactivity in the nucleus accumbens of adolescent mice.

    PubMed

    Buck, Jordan M; Morris, Alysse S; Weber, Sydney J; Raber, Jacob; Siegel, Jessica A

    2017-04-14

    The neurotoxic effects of methamphetamine (MA) exposure in the developing and adult brain can lead to behavioral alterations and cognitive deficits in adults. Previous increases in the rates of adolescent MA use necessitate that we understand the behavioral and cognitive effects of MA exposure during adolescence on the adolescent brain. Adolescents using MA exhibit high rates of nicotine (NIC) use, but the effects of concurrent MA and NIC in the adolescent brain have not been examined, and it is unknown if NIC mediates any of the effects of MA in the adolescent. In this study, the long-term effects of a neurotoxic dose of MA with or without NIC exposure during early adolescence (postnatal day 30-31) were examined later in adolescence (postnatal day 41-50) in male C57BL/6J mice. Effects on behavioral performance in the open field, Porsolt forced swim test, and conditioned place preference test, and cognitive performance in the novel object recognition test and Morris water maze were assessed. Additionally, the effects of MA and/or NIC on levels of microtubule associated-2 (MAP-2) protein in the nucleus accumbens and plasma corticosterone were examined. MA and NIC exposure during early adolescence separately decreased anxiety-like behavior in the open field test, which was not seen following co-administration of MA/NIC. There was no significant effect of early adolescent MA and/or NIC exposure on the intensity of MAP-2 immunoreactivity in the nucleus accumbens or on plasma corticosterone levels. These results show that early adolescent MA and NIC exposure separately decrease anxiety-like behavior in the open field, and that concurrent MA and NIC exposure does not induce the same behavioral change as either drug alone. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effects of prenatal exposure to WIFI signal (2.45GHz) on postnatal development and behavior in rat: Influence of maternal restraint.

    PubMed

    Othman, Haifa; Ammari, Mohamed; Sakly, Mohsen; Abdelmelek, Hafedh

    2017-05-30

    The present study was carried out to investigate the potential combined influence of maternal restraint stress and 2.45GHz WiFi signal exposure on postnatal development and behavior in the offspring of exposed rats. 24 pregnant albino Wistar rats were randomly assigned to four groups: Control, WiFi-exposed, restrained and both WiFi-exposed and restrained groups. Each of WiFi exposure and restraint occurred 2h/day along gestation till parturition. The pups were evaluated for physical development and neuromotor maturation. Moreover, elevated plus maze test, open field activity and stationary beam test were also determined on postnatal days 28, 30 and 31, respectively. After behavioral tests, the rats were anesthetized and their brains were removed for biochemical analysis. Our main findings showed no detrimental effects on gestation progress and outcomes at delivery in all groups. Subsequently, WiFi and restraint, per se and mainly in concert altered physical development of pups with slight differences between genders. Behaviorally, the gestational WiFi irradiation, restraint and especially the associated treatment affected the neuromotor maturation mainly in male progeny. At adult age, we noticed anxiety, motor deficit and exploratory behavior impairment in male offspring co-exposed to WiFi radiation and restraint, and in female progeny subjected to three treatments. The biochemical investigation showed that, all three treatments produced global oxidative stress in brain of both sexes. As for serum biochemistry, phosphorus, magnesium, glucose, triglycerides and calcium levels were disrupted. Taken together, prenatal WiFi radiation and restraint, alone and combined, provoked several behavioral and biochemical impairments at both juvenile and adult age of the offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal β Cell Proliferation.

    PubMed

    Zeng, Chun; Mulas, Francesca; Sui, Yinghui; Guan, Tiffany; Miller, Nathanael; Tan, Yuliang; Liu, Fenfen; Jin, Wen; Carrano, Andrea C; Huising, Mark O; Shirihai, Orian S; Yeo, Gene W; Sander, Maike

    2017-05-02

    Pancreatic β cell mass for appropriate blood glucose control is established during early postnatal life. β cell proliferative capacity declines postnatally, but the extrinsic cues and intracellular signals that cause this decline remain unknown. To obtain a high-resolution map of β cell transcriptome dynamics after birth, we generated single-cell RNA-seq data of β cells from multiple postnatal time points and ordered cells based on transcriptional similarity using a new analytical tool. This analysis captured signatures of immature, proliferative β cells and established high expression of amino acid metabolic, mitochondrial, and Srf/Jun/Fos transcription factor genes as their hallmark feature. Experimental validation revealed high metabolic activity in immature β cells and a role for reactive oxygen species and Srf/Jun/Fos transcription factors in driving postnatal β cell proliferation and mass expansion. Our work provides the first high-resolution molecular characterization of state changes in postnatal β cells and paves the way for the identification of novel therapeutic targets to stimulate β cell regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Neurodevelopment in Early Childhood Affected by Prenatal Lead Exposure and Iron Intake.

    PubMed

    Shah-Kulkarni, Surabhi; Ha, Mina; Kim, Byung-Mi; Kim, Eunjeong; Hong, Yun-Chul; Park, Hyesook; Kim, Yangho; Kim, Bung-Nyun; Chang, Namsoo; Oh, Se-Young; Kim, Young Ju; Kimʼs, Young Ju; Lee, Boeun; Ha, Eun-Hee

    2016-01-01

    No safe threshold level of lead exposure in children has been recognized. Also, the information on shielding effect of maternal dietary iron intake during pregnancy on the adverse effects of prenatal lead exposure on children's postnatal neurocognitive development is very limited. We examined the association of prenatal lead exposure and neurodevelopment in children at 6, 12, 24, and 36 months and the protective action of maternal dietary iron intake against the impact of lead exposure. The study participants comprise 965 pregnant women and their subsequent offspring of the total participants enrolled in the Mothers and Children's environmental health study: a prospective birth cohort study. Generalized linear model and linear mixed model analysis were performed to analyze the effect of prenatal lead exposure and mother's dietary iron intake on children's cognitive development at 6, 12, 24, and 36 months. Maternal late pregnancy lead was marginally associated with deficits in mental development index (MDI) of children at 6 months. Mothers having less than 75th percentile of dietary iron intake during pregnancy showed significant increase in the harmful effect of late pregnancy lead exposure on MDI at 6 months. Linear mixed model analyses showed the significant detrimental effect of prenatal lead exposure in late pregnancy on cognitive development up to 36 months in children of mothers having less dietary iron intake during pregnancy. Thus, our findings imply importance to reduce prenatal lead exposure and have adequate iron intake for better neurodevelopment in children.

  6. Neurodevelopment in Early Childhood Affected by Prenatal Lead Exposure and Iron Intake

    PubMed Central

    Shah-Kulkarni, Surabhi; Ha, Mina; Kim, Byung-Mi; Kim, Eunjeong; Hong, Yun-Chul; Park, Hyesook; Kim, Yangho; Kim, Bung-Nyun; Chang, Namsoo; Oh, Se-Young; Kim, Young Ju; Lee, Boeun; Ha, Eun-Hee

    2016-01-01

    Abstract No safe threshold level of lead exposure in children has been recognized. Also, the information on shielding effect of maternal dietary iron intake during pregnancy on the adverse effects of prenatal lead exposure on children's postnatal neurocognitive development is very limited. We examined the association of prenatal lead exposure and neurodevelopment in children at 6, 12, 24, and 36 months and the protective action of maternal dietary iron intake against the impact of lead exposure. The study participants comprise 965 pregnant women and their subsequent offspring of the total participants enrolled in the Mothers and Children's environmental health study: a prospective birth cohort study. Generalized linear model and linear mixed model analysis were performed to analyze the effect of prenatal lead exposure and mother's dietary iron intake on children's cognitive development at 6, 12, 24, and 36 months. Maternal late pregnancy lead was marginally associated with deficits in mental development index (MDI) of children at 6 months. Mothers having less than 75th percentile of dietary iron intake during pregnancy showed significant increase in the harmful effect of late pregnancy lead exposure on MDI at 6 months. Linear mixed model analyses showed the significant detrimental effect of prenatal lead exposure in late pregnancy on cognitive development up to 36 months in children of mothers having less dietary iron intake during pregnancy. Thus, our findings imply importance to reduce prenatal lead exposure and have adequate iron intake for better neurodevelopment in children. PMID:26825887

  7. Home-based versus hospital-based postnatal care: a randomised trial.

    PubMed

    Boulvain, Michel; Perneger, Thomas V; Othenin-Girard, Véronique; Petrou, Stavros; Berner, Michel; Irion, Olivier

    2004-08-01

    To compare a shortened hospital stay with midwife visits at home to usual hospital care after delivery. Randomised controlled trial. Maternity unit of a Swiss teaching hospital. Four hundred and fifty-nine women with a single uncomplicated pregnancy at low risk of caesarean section. Women were randomised to either home-based (n= 228) or hospital-based postnatal care (n= 231). Home-based postnatal care consisted of early discharge from hospital (24 to 48 hours after delivery) and home visits by a midwife; women in the hospital-based care group were hospitalised for four to five days. Breastfeeding 28 days postpartum, women's views of their care and readmission to hospital. Women in the home-based care group had shorter hospital stays (65 vs 106 hours, P < 0.001) and more midwife visits (4.8 vs 1.7, P < 0.001) than women in the hospital-based care group. Prevalence of breastfeeding at 28 days was similar between the groups (90%vs 87%, P= 0.30), but women in the home-based care group reported fewer problems with breastfeeding and greater satisfaction with the help received. There were no differences in satisfaction with care, women's hospital readmissions, postnatal depression scores and health status scores. A higher percentage of neonates in the home-based care group were readmitted to hospital during the first six months (12%vs 4.8%, P= 0.004). In low risk pregnancies, early discharge from hospital and midwife visits at home after delivery is an acceptable alternative to a longer duration of care in hospital. Mothers' preferences and economic considerations should be taken into account when choosing a policy of postnatal care.

  8. Postnatal Psychosocial Assessment and Clinical Decision-Making, a Descriptive Study.

    PubMed

    Sims, Deborah; Fowler, Cathrine

    2018-05-18

    The aim of this study is to describe experienced child and family health nurses' clinical decision-making during a postnatal psychosocial assessment. Maternal emotional wellbeing in the postnatal year optimises parenting and promotes infant development. Psychosocial assessment potentially enables early intervention and reduces the risk of a mental disorder occurring during this time of change. Assessment accuracy, and the interventions used are determined by the standard of nursing decision-making. A qualitative methodology was employed to explore decision-making behaviour when conducting a postnatal psychosocial assessment. This study was conducted in an Australian early parenting organisation. Twelve experienced child and family health nurses were interviewed. A detailed description of a postnatal psychosocial assessment process was obtained using a critical incident technique. Template analysis was used to determine the information domains the nurses accessed, and content analysis was used to determine the nurses' thinking strategies, to make clinical decisions from this assessment. The nurses described 24 domains of information and used 17 thinking strategies, in a variety of combinations. The four information domains most commonly used were parenting, assessment tools, women-determined issues and sleep. The seven thinking strategies most commonly used were searching for information, forming relationships between the information, recognising a pattern, drawing a conclusion, setting priorities, providing explanations for the information and judging the value of the information. The variety and complexity of the clinical decision-making involved in postnatal psychosocial assessment confirms that the nurses use information appropriately and within their scope of nursing practice. The standard of clinical decision-making determines the results of the assessment and the optimal access to care. Knowledge of the information domains and the decision-making strategies

  9. Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone.

    PubMed

    Lin, Jiamei; Wang, Shengqiang; Feng, Yunlin; Zhao, Weihong; Zhao, Weilu; Luo, Foquan; Feng, Namin

    2018-05-01

    Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30. Two hours before each MWM trial, histone deacetylase 2 (HDAC2) inhibitor, suberoylanilide hydroxamic acid (SAHA), Senegenin (SEN, traditional Chinese medicine), hippyragranin (HGN) antisense oligonucleotide (HGNA) or vehicle were given to the offspring. The protein levels of HDAC2, acetylated histone 3 (H3) and 4 (H4), cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), N-methyl-D-aspartate receptor (NMDAR) 2 subunit B (NR2B), HGN and synaptophysin in offspring's hippocampus were determined by Western blot or immunofluorescence test. It was discovered that infusion with propofol in maternal rats on E7 leads to impairment of learning and memory in offspring, increased the protein levels of HDAC2 and HGN, decreased the levels of acetylated H3 and H4 and phosphorylated CREB, NR2B and synaptophysin. HDAC2 inhibitor SAHA, Senegenin or HGN antisense oligonucleotide reversed all the changes. Thus, present results indicate exposure to propofol during the early gestation impairs offspring's learning and memory via inhibiting histone acetylation. SAHA, Senegenin and HGN antisense oligonucleotide might have therapeutic value for the adverse effect of propofol. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Early life exposures and the risk of adult glioma.

    PubMed

    Anic, Gabriella M; Madden, Melissa H; Sincich, Kelly; Thompson, Reid C; Nabors, L Burton; Olson, Jeffrey J; LaRocca, Renato V; Browning, James E; Pan, Edward; Egan, Kathleen M

    2013-09-01

    Exposure to common infections in early life may stimulate immune development and reduce the risk for developing cancer. Birth order and family size are proxies for the timing of exposure to childhood infections with several studies showing a reduced risk of glioma associated with a higher order of birth (and presumed younger age at infection). The aim of this study was to examine whether birth order, family size, and other early life exposures are associated with the risk of glioma in adults using data collected in a large clinic-based US case-control study including 889 glioma cases and 903 community controls. A structured interviewer-administered questionnaire was used to collect information on family structure, childhood exposures and other potential risk factors. Logistic regression was used to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between early life factors and glioma risk. Persons having any siblings were at significantly lower risk for glioma when compared to those reporting no siblings (OR=0.64; 95% CI 0.44-0.93; p=0.020). Compared to first-borns, individuals with older siblings had a significantly lower risk (OR=0.75; 95% CI 0.61-0.91; p=0.004). Birth weight, having been breast fed in infancy, and season of birth were not associated with glioma risk. The current findings lend further support to a growing body of evidence that early exposure to childhood infections reduces the risk of glioma onset in children and adults.

  11. Exposure Cessation During Adulthood Did Not Prevent Immunotoxicity Caused by Developmental Exposure to Low-Level Trichloroethylene in Drinking Water.

    PubMed

    Gilbert, Kathleen M; Bai, Shasha; Barnette, Dustyn; Blossom, Sarah J

    2017-06-01

    Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Targeted surveillance for postnatal hearing loss: a program evaluation.

    PubMed

    Beswick, Rachael; Driscoll, Carlie; Kei, Joseph; Glennon, Shirley

    2012-07-01

    The importance of monitoring hearing throughout early childhood cannot be understated. However, there is a lack of evidence available regarding the most effective method of monitoring hearing following the newborn screen. The goal of this study was to describe a targeted surveillance program using a risk factor registry to identify children with a postnatal hearing loss. All children who were born in Queensland, Australia between September 2004 and December 2009, received a bilateral 'pass' on newborn hearing screening, and had at least one risk factor, were referred for targeted surveillance and were included in this study. The cohort was assessed throughout early childhood in accordance with Queensland's diagnostic assessment protocols. During the study period, 7320 (2.8% of 261,328) children were referred for targeted surveillance, of which 56 were identified with a postnatal hearing loss (0.77%). Of these, half (50.0%) were identified with a mild hearing loss, and 64.3% were identified with a sensorineural hearing loss. In regards to risk factors, syndrome, craniofacial anomalies, and severe asphyxia had the highest yield of positive cases of postnatal hearing loss for children referred for targeted surveillance, whereas, low birth weight, bacterial meningitis, and professional concern had a particularly low yield. Limitations of the targeted surveillance program were noted and include: (1) a lost contact rate of 32.4%; (2) delays in first surveillance assessment; (3) a large number of children who required on-going monitoring; and (4) extensive diagnostic assessments were completed on children with normal hearing. Examination of the lost contact rate revealed indigenous children were more likely to be documented as lost contact. In addition, children with one risk factor only were significantly more likely to not attend a surveillance appointment. Positive cases of postnatal hearing loss were detected through the targeted surveillance program. However, the

  13. PROLACTIN REGULATES LIVER GROWTH DURING POSTNATAL DEVELOPMENT IN MICE.

    PubMed

    Moreno-Carranza, Bibiana; Bravo-Manríquez, Marco; Baez, Arelí; Ledesma-Colunga, María G; Ruiz-Herrera, Xarubet; Reyes-Ortega, Pamela; De Los Ríos, Ericka A; Macotela, Yazmín; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2018-02-21

    The liver grows during the early postnatal period first at slower and then at faster rates than the body to achieve the adult liver-to-body weight ratio (LBW), a constant reflecting liver health. The hormone prolactin (PRL) stimulates adult liver growth and regeneration and its levels are high in the circulation of newborn infants, but whether PRL plays a role on neonatal liver growth is unknown. Here, we show that the liver produces PRL and upregulates the PRL receptor in mice during the first 2 weeks after birth, when liver growth lags behind body growth. At postnatal week 4, the production of PRL by the liver ceases coinciding with the elevation of circulating PRL and the faster liver growth that catches up with body growth. PRL receptor null mice (Prlr-/-) show a significant decrease in the LBW at 1, 4, 6, and 10 postnatal weeks and reduced liver expression of proliferation (cyclin D1, Ccnd1) and angiogenesis (platelet/endothelial cell adhesion molecule 1, Pecam1) markers relative to Prlr+/+ mice. However, the LBW increases in Prlr-/- mice at postnatal week 2 concurring with the enhanced liver expression of Igf-1 and the liver upregulation and downregulation of suppressor of cytokine signaling 2 (Socs2) and Socs3, respectively. These findings indicate that PRL acts locally and systemically to restrict and stimulate postnatal liver growth. PRL inhibits liver and body growth by attenuating growth hormone-induced Igf-1 liver expression via Socs2 and Socs3-related mechanisms.

  14. Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea

    PubMed Central

    Brown, LaShardai N.; Xing, Yazhi; Noble, Kenyaria V.; Barth, Jeremy L.; Panganiban, Clarisse H.; Smythe, Nancy M.; Bridges, Mary C.; Zhu, Juhong; Lang, Hainan

    2017-01-01

    Hearing relies on the transmission of auditory information from sensory hair cells (HCs) to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs) in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement. Whether auditory glial cells are eliminated during auditory nerve refinement is unknown. Using early postnatal mice of either sex, we show that glial cell numbers decrease after the first postnatal week, corresponding temporally with nerve refinement in the developing auditory nerve. Additionally, expression of immune-related genes was upregulated and macrophage numbers increase in a manner coinciding with the reduction of glial cell numbers. Transient depletion of macrophages during early auditory nerve development, using transgenic CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells. Macrophage depletion caused abnormalities in myelin formation and transient edema of the stria vascularis. Macrophage-depleted mice also showed auditory function impairment that partially recovered in adulthood. These findings demonstrate that macrophages contribute to the regulation of glial cell number during postnatal development of the cochlea and that glial cells play a critical role in hearing onset and auditory nerve maturation. PMID:29375297

  15. Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

    PubMed

    Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

    2011-08-01

    Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  16. The influence of postnatal nutrition on reproductive tract and endometrial gland development in dairy calves.

    PubMed

    Wilson, Meghan L; McCoski, Sarah R; Geiger, Adam J; Akers, R Michael; Johnson, Sally E; Ealy, Alan D

    2017-04-01

    Uterine gland development occurs after birth in cattle and other mammals. The timeline of gland development has been described in various species, but little is known about how postnatal diet influences uterine gland development. This is especially concerning in dairy heifers, where a variety of milk replacer and whole milk nutrition options exist. Little work also exists in cattle to describe how early exposure to steroids influences reproductive tract and uterine gland development. The objective of this work was to determine the effects of early postnatal plane of nutrition and estrogen supplementation on uterine gland development in calves. In both studies, Holstein heifer calves were assigned to restricted milk replacer (R-MR) or enhanced milk replacer (EH-MR) diets. In study 1, calves (R-MR, n = 6; EH-MR, n = 5) were euthanized at 8 wk. In study 2, calves were weaned at 8 wk and administered estradiol (R-MR, n = 6; EH-MR, n = 6) or placebo (R-MR, n = 6; EH-MR, n = 5) for an additional 14 d before euthanasia. Average daily gain and final body weight was greater in both studies in heifers fed the enhanced diet. At 8 wk, EH-MR calves had a greater number of glands and a smaller average gland size, but total gland area was not different from the R-MR group. At 10 wk, uterine gland number and size were not affected by diet or estrogen. Expression profiles of several paracrine mediators of gland development were examined. Increases in transcript abundance for IGF1 and IGFBP3 and a decrease in abundance of WNT7A were detected in calves fed the enhanced diet at 8 wk of age. Plane of nutrition did not affect transcript profiles at 10 wk of age, but estradiol supplementation decreased MET and WNT7A transcript abundance. To conclude, heifer calves on a restricted diet exhibited a uterine morphology and transcript profile suggestive of delayed uterine gland development. These changes appear to be corrected by wk 10 of life. Also, this work provides evidence supporting the

  17. Duodenal Ca2+ absorption is not stimulated by calcitriol during early postnatal development of pigs.

    PubMed

    Schroeder, B; Dahl, M R; Breves, G

    1998-08-01

    The role of calcitriol in stimulating intestinal active Ca2+ absorption during postnatal life was studied in newborn, suckling, and weaned control (Con) piglets and piglets suffering from inherited calcitriol deficiency (Def piglets). In addition, a group of Def piglets was treated with vitamin D3 (Def-D3 piglets), which normalized plasma calcitriol levels. Regardless of age, duodenal calbindin-D9k concentrations ranged between 1,839 and 2,846 microg/g mucosa in Con piglets, between 821 and 1,219 microg/g mucosa in Def piglets, and between 2,960 and 3,692 microg/g mucosa in Def-D3 animals. In weaned animals, active Ca2+ absorption as calculated from in vitro 45Ca2+ flux rate measurements in Ussing chambers could be related to calbindin-D9k levels. Thus active Ca2+ absorption was completely absent in Def animals but was reconstituted in Def-D3 animals. In contrast, in newborn Def piglets active Ca2+ absorption functioned normally despite the low plasma calcitriol and mucosal calbindin-D9k levels and could not be affected by treatment with vitamin D3. Similar results were obtained from suckling Def piglets. The microtubule-disrupting agent colchicine caused significant inhibition of transepithelial net Ca2+ absorption in duodenal epithelia from newborn piglets without exerting an effect in suckling and weaned animals. Colchicine had no effect on Ca2+ uptake across the brush border membrane of mucosal enterocytes or on glucose-dependent electrogenic net ion flux rates in duodenal preparations from newborn Con piglets. In conclusion, our findings reveal intestinal active Ca2+ absorption during early postnatal life of pigs that involves calcitriol-independent mechanisms and that may include intact microtubule actions.

  18. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp; Liu, Jun-Qian; Ohta, Ken-ichi

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved bymore » separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.« less

  19. African ancestry, early life exposures, and respiratory morbidity in early childhood.

    PubMed

    Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

    2012-02-01

    Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and

  20. African ancestry, early life exposures, and respiratory morbidity in early childhood

    PubMed Central

    Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

    2012-01-01

    Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to

  1. Perinatal exposure to methadone affects central cholinergic activity in the weanling rat.

    PubMed

    Robinson, S E; Mo, Q; Maher, J R; Wallace, M J; Kunko, P M

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.

  2. Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep

    PubMed Central

    Volk, Kenneth A.; Roghair, Robert D.; Jung, Felicia; Scholz, Thomas D.; Lamb, Fred S.

    2010-01-01

    Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg·kg−1·day−1 for 48 h) was administered to pregnant ewes at 27–28-day gestation (term 145 days). Coronary arteries were isolated from 1- to 2-wk-old dex-exposed offspring and aged-matched controls. Compared with controls, coronary arteries from dex-exposed lambs demonstrated enhanced vasoconstriction to endothelin-1 and ACh that was abolished by endothelial removal or preincubation with the nitric oxide synthase inhibitor l-NNA, membrane-permeable superoxide dismutase + catalase, or apamin + charybdotoxin, but not indomethacin. The rate of coronary vascular smooth muscle cell (VSMC) proliferation was also significantly greater in dex-exposed lambs. Protein levels of the proliferating cell nuclear antigen were increased and α-smooth muscle actin decreased in dex-exposed coronary VSMC, consistent with a proliferative state. Finally, expression of the NADPH oxidase Nox 4, but not Nox 1, mRNA was also decreased in coronary VSMC from dex-exposed lambs. These findings suggest an important interaction exists between early-gestation glucocorticoid exposure and reactive oxygen species that is associated with alterations in endothelial function and coronary VSMC proliferation. These changes in coronary physiology are consistent with those associated with the development of atherosclerosis and may provide an important link between an adverse intrauterine environment and increased risk for coronary artery disease. PMID:20335378

  3. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure and insulin resistance in offspring rats.

    PubMed

    Hao, Xue-Qin; Du, Jing-Xia; Li, Yan; Li, Meng; Zhang, Shou-Yan

    2014-01-01

    Adult metabolic syndrome may in part have origins in fetal or early life. This study was designed to explore the effect of prenatal exposure to lipopolysaccharide and high-fat diet on metabolic syndrome in offspring rats. 32 pregnant rats were randomly divided into four groups, including Control group; LPS group (pregnant rats were injected with LPS 0.4 mg/kg intraperitoneally on the 8(th), 10(th) and 12(th) day of pregnancy); High-fat group (maternal rats had high-fat diet during pregnancy and lactation period, and their pups also had high-fat diet up to the third month of life); LPS + High-fat group (rats were exposed to the identical experimental scheme with LPS group and High-fat group). Blood pressure elevated in LPS group and High-fat group, reduced in LPS+High-fat group, accompanied by the increase of serum leptin level in LPS and High-fat group and increase of serum IL-6, TNF-a in High-fat group; both serum insulin and cholesterol increased in High-fat and LPS+High-fat group, as well as insulin in LPS group. HOMA-IR value increased in LPS, High-fat and LPS+High-fat group, and QUICKI decreased in these groups; H-E staining showed morphologically pathological changes in thoracic aorta and liver tissue in the three groups. Increased serum alanine and aspartate aminotransferase suggest impaired liver function in LPS+High-fat group. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure, insulin resistance and impaired liver function in three-month old offspring rats. The lowered blood pressure might benefit from the predictive adaptive response to prenatal inflammation.

  4. Early exposure to media violence and later child adjustment.

    PubMed

    Fitzpatrick, Caroline; Barnett, Tracie; Pagani, Linda S

    2012-05-01

    The extent to which early childhood exposure to violent media is associated with subsequent adverse child functioning remains disconcerting. In this study, we examine whether preschool child exposure to what parents generally characterize as violent television programming predicts a range of second-grade mental health outcomes. Participants are from the Quebec Longitudinal Study of Child Development (N = 1786). At 41 and 53 months, parents reported whether the child had viewed television shows and videos consisting of what they judged as violent content. According to parents, children watched on average 1.8 hours of mixed programming per day. Parent-reported child exposure to televised violence was associated with teacher-reported antisocial symptoms (β = 0.180, 95% confidence interval [CI]: 0.026-0.333), emotional distress (β = 0.224, 95% CI: 0.010-0.438), inattention (β = 0.349, 95% CI: 0.048-0.651), and lower global academic achievement (β = -0.127, 95% CI: -0.237-0.017) in second grade. Violent televiewing was also associated with less child-reported academic self-concept (β = -0.175, 95% CI: -0.296-0.053) and intrinsic motivation (β = -0.162, 95% CI: -0.016-0.307) in second grade. Effects remained significant after adjusting for preexisting child and family characteristics such as baseline child aggression. This prospective study suggests risks associated with early childhood violent media exposure for long-term mental health in children. These findings, suggesting diffusive relationships between early childhood violent media exposure and negative socioemotional and academic outcomes, empirically support the notion that access to early childhood violent television represents a threat to population health and should be discouraged by adult caregivers.

  5. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herring, M.J.; Putney, L.F.; St George, J.A.

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergenmore » (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)« less

  6. Brain-derived neurotrophic factor (BDNF) and TrkB in the piglet brainstem after post-natal nicotine and intermittent hypercapnic hypoxia.

    PubMed

    Tang, Samantha; Machaalani, Rita; Waters, Karen A

    2008-09-26

    Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play a significant role in the regulation of cell growth, survival and death during central nervous system development. The expression of BDNF and TrkB is affected by noxious insults. Two insults during the early post-natal period that are of interest to our laboratory are exposure to nicotine and to intermittent hypercapnic hypoxia (IHH). Piglet models were used to mimic the conditions associated with the risk factors for the sudden infant death syndrome (SIDS) including post-natal cigarette smoke exposure (nicotine model) and prone sleeping where the infant is subjected to re-breathing of expired gases (IHH model). We aimed to determine the effects of nicotine and IHH, alone or in combination, on pro- and rhBDNF and TrkB expression in the developing piglet brainstem. Four piglet groups were studied, with equal gender ratios in each: control (n=14), nicotine (n=14), IHH (n=10) and nic+IHH (n=14). Applying immunohistochemistry, and studying six nuclei of the caudal medulla, we found that compared to controls, TrkB was the only protein significantly decreased after nicotine and nic+IHH exposure regardless of gender. For pro-BDNF and rhBDNF however, observed changes were more evident in males than females exposed to nicotine and nic+IHH. The implications of these findings are that a prior nicotine exposure makes the developing brainstem susceptible to greater changes in the neurotrophic effects of BDNF and its receptor TrkB in the face of a hypoxic insult, and that the effects are greater in males than females.

  7. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    PubMed

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  8. Birth weight and postnatal growth in preterm born children are associated with cortisol in early infancy, but not at age 8 years.

    PubMed

    Ruys, Charlotte A; van der Voorn, Bibian; Lafeber, Harrie N; van de Lagemaat, Monique; Rotteveel, Joost; Finken, Martijn J J

    2017-08-01

    Preterm birth has been associated with altered hypothalamic-pituitary-adrenal (HPA-) axis activity as well as cardiometabolic diseases and neurodevelopmental impairments later in life. We assessed cortisol from term age to age 8 y in children born preterm, to explore the development of HPA-axis activity in association with intrauterine and early-postnatal growth until 6 mo. corrected age. In 152 children born at a gestational age ≤32 wks. and/or with a birth weight ≤1,500g, random serum cortisol was assessed at term age (n=150), 3 mo. (n=145) and 6 mo. corrected age (n=144), and age 8 y (n=59). Salivary cortisol was assessed at age 8 y (n=75): prior to bedtime, at awakening, 15min after awakening, and before lunch. Cortisol was analyzed in association with birth weight-standard deviation score (SDS), being born small for gestational age (SGA), and combinations of intrauterine and postnatal growth: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+ or AGA GR-) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA CUG+ or SGA CUG-) at 6 mo. corrected age. Cross-sectional associations at all time points were analyzed using linear regression, and longitudinal associations were analyzed using generalized estimating equations. Longitudinally, birth weight-SDS was associated with cortisol (β [95%CI]): lower cortisol over time was seen in infants with a birth weight ≤-2 SDS (-50.69 [-94.27; -7.11], p=0.02), infants born SGA (-29.70 [-60.58; 1.19], p=0.06), AGA GR+ infants (-55.10 [-106.02; -4.17], p=0.03) and SGA CUG- infants (-61.91 [-104.73; -19.10], p=0.01). In cross-sectional analyses at age 8 y, no associations were found between either serum or salivary cortisol and birth weight-SDS, SGA-status, or growth from birth to 6 mo. corrected age. In children born preterm, poor intrauterine and postnatal growth were associated with lower cortisol in early infancy, but not at age 8 y. Even though HPA-axis activity no longer

  9. Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

    PubMed

    Buklijas, Tatjana

    2014-09-01

    Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Comparing postnatal development of gonadal hormones and associated social behaviors in rats, mice, and humans.

    PubMed

    Bell, Margaret R

    2018-05-14

    Postnatal development includes dramatic changes in gonadal hormones and the many social behaviors they help regulate, both in rodents and humans. Parental care-seeking is the most salient social interaction in neonates and infants, play and pro-social behaviors are commonly studied in juveniles, and the development of aggression and sexual behavior begins in peripubertal stages but continues through late adolescence into adulthood. While parental behaviors are shown after reproductive success in adulthood, alloparenting behaviors are actually high in juveniles as well. These behaviors are sensitive to both early life organizational effects of gonadal hormones and later life activational regulation. However, changes in circulating gonadal hormones and the display of the above behaviors over development differs between rats, mice and humans. These endpoints are of interest to endocrinologist, toxicologists, neuroscientists because of their relevance to mental health disorders and their vulnerability to effects of endocrine disrupting chemical exposure. As such, the goal of this minireview is to succinctly describe and relate the postnatal development of gonadal hormones and social behaviors to each other, over time and across animal models. Ideally, this will help identify appropriate animal models and age ranges for continued study of both normative development and in contexts of environmental disruption.

  11. The die is cast: arsenic exposure in early life and disease susceptibility.

    PubMed

    Thomas, David J

    2013-12-16

    Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

  12. A BIOASSAY THAT IDENTIFIES POSTNATAL FUNCTIONAL DEFICITS IN MICE PRENATALLY EXPOSED TO XENOBIOTICS

    EPA Science Inventory

    Experimental strategies to evaluate adverse postnatal effects due to prenatal exposure exist for many organ systems. Often, however, there is insufficient information to suggest that a particular organ system(s) may be sensitive to the test agent. A single bioassay to identify ...

  13. Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling.

    PubMed

    Teegarden, S L; Scott, A N; Bale, T L

    2009-09-15

    Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho-dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, DeltaFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.

  14. Lack of the alanine-serine-cysteine transporter 1 causes tremors, seizures, and early postnatal death in mice.

    PubMed

    Xie, Xinmin; Dumas, Theodore; Tang, Lamont; Brennan, Thomas; Reeder, Thadd; Thomas, Winston; Klein, Robert D; Flores, Judith; O'Hara, Bruce F; Heller, H Craig; Franken, Paul

    2005-08-09

    The Na(+)-independent alanine-serine-cysteine transporter 1 (Asc-1) is exclusively expressed in neuronal structures throughout the central nervous system (CNS). Asc-1 transports small neutral amino acids with high affinity especially for D-serine and glycine (K(i): 8-12 microM), two endogenous glutamate co-agonists that activate N-methyl-D-aspartate (NMDA) receptors through interacting with the strychnine-insensitive glycine binding-site. By regulating D-serine (and possibly glycine) levels in the synaptic cleft, Asc-1 may play an important role in controlling neuronal excitability. We generated asc-1 gene knockout (asc-1(-/-)) mice to test this hypothesis. Behavioral phenotyping combined with electroencephalogram (EEG) recordings revealed that asc-1(-/-) mice developed tremors, ataxia, and seizures that resulted in early postnatal death. Both tremors and seizures were reduced by the NMDA receptor antagonist MK-801. Extracellular recordings from asc-1(-/-) brain slices indicated that the spontaneous seizure activity did not originate in the hippocampus, although, in this region, a relative increase in evoked synaptic responses was observed under nominal Mg(2+)-free conditions. Taken together with the known neurochemistry and neuronal distribution of the Asc-1 transporter, these results indicate that the mechanism underlying the behavioral hyperexcitability in mutant mice is likely due to overactivation of NMDA receptors, presumably resulting from elevated extracellular D-serine. Our study provides the first evidence to support the notion that Asc-1 transporter plays a critical role in regulating neuronal excitability, and indicate that the transporter is vital for normal CNS function and essential to postnatal survival of mice.

  15. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age.

    PubMed

    Jusko, Todd A; Sisto, Renata; Iosif, Ana-Maria; Moleti, Arturo; Wimmerová, Sonˇa; Lancz, Kinga; Tihányi, Juraj; Sovčiková, Eva; Drobná, Beata; Palkovičová, L'ubica; Jurečková, Dana; Thevenet-Morrison, Kelly; Verner, Marc-André; Sonneborn, Dean; Hertz-Picciotto, Irva; Trnovec, Tomáš

    2014-11-01

    Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p = 0.003). In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.

  16. Maternal exposure to ambient air temperature during pregnancy and early childhood pneumonia.

    PubMed

    Miao, Yufeng; Shen, Yong-Ming; Lu, Chan; Zeng, Ji; Deng, Qihong

    2017-10-01

    Pneumonia has been widely recognized as the leading cause of death in children worldwide, but its etiology still remains unclear. We examined the association between maternal exposure to ambient air temperature during pregnancy and lifetime pneumonia in the offspring. We conducted a cohort study of 2598 preschool children aged 3-6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed using questionnaire. We backwards estimated each child's exposure to air temperature during prenatal and postnatal periods. Multiple regression model was used to examine the association between childhood pneumonia and exposure to air temperature in terms of odd ratios (OR) and 95% confidence interval (CI). Prevalence of childhood pneumonia in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal exposure to air temperature, with adjusted OR (95% CI) = 1.77 (1.23-2.54) for an interquartile range (IQR) increase in temperature, particularly during the second trimester with adjusted OR (95% CI) = 2.26 (1.32-3.89). Boys are more susceptible to the risk of pneumonia due to air temperature than girls. We further observed that maternal exposure to extreme heat days during pregnancy increased the risk of pneumonia in the offspring. Maternal exposure to air temperature during pregnancy, particularly the second trimester, was associated with pneumonia in the children, providing the evidence for fetal origins of pneumonia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Early-life chemical exposures and risk of metabolic syndrome.

    PubMed

    De Long, Nicole E; Holloway, Alison C

    2017-01-01

    The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity.

  18. Quality of life, postnatal depression and baby gender.

    PubMed

    de Tychey, Claude; Briançon, Serge; Lighezzolo, Joëlle; Spitz, Elisabeth; Kabuth, Bernard; de Luigi, Valerie; Messembourg, Catherine; Girvan, Françoise; Rosati, Aurore; Thockler, Audrey; Vincent, Stephanie

    2008-02-01

    To study the impact of postnatal depression on the quality of life of young French mothers and to evaluate if the gender of their child influences this. Postnatal depression (PND) constitutes a major public health problem considering its high prevalence and consequences upon quality of life and parental skills. This research is a cross-sectional study during the postnatal period. This study was carried out during a two-month period. Data were collected by interview and questionnaires. The authors compared the prevalence rate of PND and life quality in a cohort of 181 women and measured the short-term impact of the child's birth. Postnatal depression strongly negatively influences all dimensions of life quality explored through the SF36, e.g. physical functioning (PF), physical Role (RP), bodily pain (BP), mental health (MH), emotional role (RE), social functioning (SF), vitality (VT), general health (GH), standardized physical component (PCS) and standardized mental component (MCS). The baby's gender (having a boy) also significantly reduces quality of life, irrespective of depressive state. There is a relationship between baby gender and PND. This research is the first to show that the birth of a boy reduces several dimensions of the mothers' quality of life. The importance of the impairment of quality of life in case of PND, as well as its effects on mother-child interaction, could justify prevention programs and early psychotherapeutic care. Further research needs to explore the effectiveness of programmes targeting the construction of parenting skills as a preventative measure against PND, especially for parents of boys.

  19. Neurobiology and Neurodevelopmental Impact of Childhood Traumatic Stress and Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    Henry, Jim; Sloane, Mark; Black-Pond, Connie

    2007-01-01

    Purpose: Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic…

  20. Postnatal development of echolocation abilities in a bottlenose dolphin (Tursiops truncatus): temporal organization.

    PubMed

    Favaro, Livio; Gnone, Guido; Pessani, Daniela

    2013-03-01

    In spite of all the information available on adult bottlenose dolphin (Tursiops truncatus) biosonar, the ontogeny of its echolocation abilities has been investigated very little. Earlier studies have reported that neonatal dolphins can produce both whistles and burst-pulsed sounds just after birth and that early-pulsed sounds are probably a precursor of echolocation click trains. The aim of this research is to investigate the development of echolocation signals in a captive calf, born in the facilities of the Acquario di Genova. A set of 81 impulsive sounds were collected from birth to the seventh postnatal week and six additional echolocation click trains were recorded when the dolphin was 1 year old. Moreover, behavioral observations, concurring with sound production, were carried out by means of a video camera. For each sound we measured five acoustic parameters: click train duration (CTD), number of clicks per train, minimum, maximum, and mean click repetition rate (CRR). CTD and number of clicks per train were found to increase with age. Maximum and mean CRR followed a decreasing trend with dolphin growth starting from the second postnatal week. The calf's first head scanning movement was recorded 21 days after birth. Our data suggest that in the bottlenose dolphin the early postnatal weeks are essential for the development of echolocation abilities and that the temporal features of the echolocation click trains remain relatively stable from the seventh postnatal week up to the first year of life. © 2013 Wiley Periodicals, Inc.

  1. Antenatal interpersonal sensitivity is more strongly associated than perinatal depressive symptoms with postnatal mother-infant interaction quality.

    PubMed

    Raine, Karen; Cockshaw, Wendell; Boyce, Philip; Thorpe, Karen

    2016-10-01

    Maternal mental health has enduring effects on children's life chances and is a substantial cost driver for child health, education and social services. A key linking mechanism is the quality of mother-infant interaction. A body of work associates maternal depressive symptoms across the antenatal and postnatal (perinatal) period with less-than-optimal mother-infant interaction. Our study aims to build on previous research in the field through exploring the association of a maternal personality trait, interpersonal sensitivity, measured in early pregnancy, with subsequent mother-infant interaction quality. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the association between antenatal interpersonal sensitivity and postnatal mother-infant interaction quality in the context of perinatal depressive symptoms. Interpersonal sensitivity was measured during early pregnancy and depressive symptoms in the antenatal year and across the first 21 months of the postnatal period. In a subsample of the ALSPAC, mother-infant interaction was measured at 12 months postnatal through a standard observation. For the subsample that had complete data at all time points (n = 706), hierarchical regression examined the contribution of interpersonal sensitivity to variance in mother-infant interaction quality. Perinatal depressive symptoms predicted little variance in mother-infant interaction. Antenatal interpersonal sensitivity explained a greater proportion of variance in mother-infant interaction quality. The personality trait, interpersonal sensitivity, measured in early pregnancy, is a more robust indicator of subsequent mother-infant-interaction quality than perinatal depressive symptoms, thus affording enhanced opportunity to identify vulnerable mother-infant relationships for targeted early intervention.

  2. Epigenetics, obesity and early-life cadmium or lead exposure

    PubMed Central

    Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

    2017-01-01

    Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures. PMID:27981852

  3. Epigenetics, obesity and early-life cadmium or lead exposure.

    PubMed

    Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

    2017-01-01

    Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

  4. Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

    PubMed

    Spiroski, A M; Oliver, M H; Jaquiery, A L; Prickett, T C R; Espiner, E A; Harding, J E; Bloomfield, F H

    2017-12-12

    Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 μg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter

  5. The impact of early repeated pain experiences on stress responsiveness and emotionality at maturity in rats.

    PubMed

    Page, Gayle G; Blakely, Wendy P; Kim, Miyong

    2005-01-01

    The intensive care necessary for premature newborns is characterized by multiple procedures, many of which are painful. Given emerging evidence that such early pain during this time of high brain plasticity may affect long-term neurodevelopmental and social-emotional functioning, this study explored the impact of early repeated pain on emotionality and stress responsivity at maturity. From birth through postnatal day 7, Fischer 344 pups underwent either paw needle prick every day versus every other day or daily paw touch, or were left unperturbed. Each paw received the designated perturbation once per day. At maturity, some animals underwent emotionality testing: either a 4-day series of open field exposures or a single elevated plus-maze (EPM) exposure. The paw prick groups exhibited less open field habituation and occupied the EPM open arms more. Two weeks later, all animals were either subjected to forced swim or not. At 1h post-swim, animals underwent either blood withdrawal for plasma corticosterone (CS) levels and ex vivo natural killer cell activity (NKCA) or were injected intravenously with radiolabeled NK-sensitive syngeneic MADB106 tumor cells and assessed for lung tumor retention. Sex was a major factor in the manifestation of perturbation-related differences in the biologic outcomes. Whereas postnatal pain differentially affected baseline tumor retention between males and females, only males exhibited perturbation-related differences in swim stress-induced increases in tumor retention and CS. Finally, male-female differences were evident in CS, NKCA, and tumor responses to swim stress. These findings suggest that early pain affects neurodevelopmental function in the mature organism; however, these relationships are complicated by sex differences, the postnatal pain schedule, and the outcome measured.

  6. Are There Effects of Intrauterine Cocaine Exposure on Delinquency during Early Adolescence? A Preliminary Report

    PubMed Central

    Gerteis, Jessie; Chartrand, Molinda; Martin, Brett; Cabral, Howard J.; Rose-Jacobs, Ruth; Crooks, Denise; Frank, Deborah A.

    2011-01-01

    Objective To ascertain whether level of intrauterine cocaine exposure (IUCE) is associated with early adolescent delinquent behavior, after accounting for prenatal exposures to other psychoactive substances and relevant psychosocial factors. Methods Ninety-three early adolescents (12.5–14.5 years old) participating since birth in a longitudinal study of IUCE reported delinquent acts via an audio computer assisted self interview (ACASI). Level of IUCE and exposure to cigarettes, alcohol, and marijuana were determined by maternal report, maternal and infant urine assays, and infant meconium assays at birth. Participants reported their exposure to violence on the Violence Exposure Scale for Children – Revised (VEX-R) at ages 8.5, 9.5, 11 years and during early adolescence, and the strictness of supervision by their caregivers during early adolescence. Results Of the 93 participants, 24 (26%) reported ≥3 delinquent behaviors during early adolescence. In the final multivariate model (including level of IUCE and cigarette exposure, childhood exposure to violence, and caregiver strictness/supervision) ≥ 3 delinquent behaviors were not significantly associated with level of IUCE but were significantly associated with intrauterine exposure to half a pack or more of cigarettes per day and higher levels of childhood exposure to violence, effects substantially unchanged after control for early adolescent violence exposure. Conclusions In this cohort, prospectively ascertained prenatal exposure to cigarettes and childhood exposure to violence are associated with self-reported delinquent behaviors during early adolescence. Contrary to initial popular predictions, intrauterine cocaine is not a strong predictor of adolescent delinquent behaviors in this cohort. PMID:21558951

  7. Beneficial effects of postnatal choline supplementation on long-Term neurocognitive deficit resulting from fetal-Neonatal iron deficiency.

    PubMed

    Kennedy, Bruce C; Tran, Phu V; Kohli, Maulika; Maertens, Jamie J; Gewirtz, Jonathan C; Georgieff, Michael K

    2018-01-15

    Early-life iron deficiency is a common nutrient condition worldwide and can result in cognitive impairment in adulthood despite iron treatment. In rodents, prenatal choline supplementation can diminish long-term hippocampal gene dysregulation and neurocognitive deficits caused by iron deficiency. Since fetal iron status is generally unknown in humans, we determined whether postnatal choline supplementation exerts similar beneficial effects. Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (3-6ppm Fe) from gestational day (G) 3 through postnatal day (P) 7, and an iron-sufficient (IS) diet (200ppm Fe) thereafter. Control pups were provided IS diet throughout. Choline (5ppm) was given to half the nursing dams and weanlings in each group from P11-P30. P65 rat cognitive performance was assessed by novel object recognition (NOR). Real-time PCR was performed to validate expression levels of synaptic plasticity genes known to be dysregulated by early-life iron deficiency. Postnatal choline supplementation prevented impairment of NOR memory in formerly iron-deficient (FID) adult rats but impaired NOR memory in IS controls. Gene expression analysis revealed a recovery of 4 out of 10 dysregulated genes compared to 8 of the same 10 genes that we previously demonstrated to recover following prenatal choline supplementation. Recognition memory deficits induced by early-life iron deficiency can be prevented by postnatal choline supplementation and disrupted expression of a subset of synaptic plasticity genes can be ameliorated. The positive response to postnatal choline represents a potential adjunctive therapeutic supplement to treat iron-deficient anemic children in order to spare long-term neurodevelopmental deficits. Copyright © 2017. Published by Elsevier B.V.

  8. Early nutrition programming of long-term health.

    PubMed

    Koletzko, Berthold; Brands, Brigitte; Poston, Lucilla; Godfrey, Keith; Demmelmair, Hans

    2012-08-01

    Increasing evidence from the EU Project EARNEST and many other investigators demonstrates that early nutrition and lifestyle have long-term effects on later health and the risk of common non-communicable diseases (known as 'developmental programming'). Because of the increasing public health importance and the transgenerational nature of the problem, obesity and associated disorders are the focus of the new EU funded project 'EarlyNutrition'. Currently, three key hypotheses have been defined: the fuel mediated 'in utero' hypothesis suggests that intrauterine exposure to an excess of fuels, most notably glucose, causes permanent changes of the fetus that lead to obesity in postnatal life; the accelerated postnatal weight gain hypothesis proposes an association between rapid weight gain in infancy and an increased risk of later obesity and adverse outcomes; and the mismatch hypothesis suggests that experiencing a developmental 'mismatch' between a sub-optimal perinatal and an obesogenic childhood environment is related to a particular predisposition to obesity and corresponding co-morbidities. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme to investigate those key hypotheses, project EarlyNutrition will provide the scientific foundations for evidence-based recommendations for optimal nutrition considering long-term health outcomes, with a focus on obesity and related disorders. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level of the relationships between early life nutritional status and the risk of later adiposity. This will help refine strategies for intervention in early life to prevent obesity.

  9. The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen Yanan; Tang, Bor Luen

    2006-03-03

    The amyloid precursor protein (APP) is the source of amyloid-beta (A{beta}) peptide, produced via its sequential cleavage {beta}- and {gamma}-secretases. Various biophysical forms of A{beta} (and the mutations of APP which results in their elevated levels) have been implicated in the etiology and early onset of Alzheimer's disease. APP's evolutionary conservation and the existence of APP-like isoforms (APLP1 and APLP2) which lack the A{beta} sequence, however, suggest that these might have important physiological functions that are unrelated to A{beta} production. Soluble N-terminal fragments of APP have been known to be neuroprotective, and the interaction of its cytoplasmic C-terminus with amore » myriad of proteins associates it with diverse processes such as axonal transport and transcriptional regulation. The notion for an essential postnatal function of APP has been demonstrated genetically, as mice deficient in both APP and APLP2 or all three APP isoforms exhibit early postnatal lethality and neuroanatomical abnormalities. Recent findings have also brought to light two possible functions of the APP family in Brain-regulation of neural progenitor cell proliferation and axonal outgrowth after injury. Interestingly, these two apparently related neurogenic/neuroregenerative functions of APP involve two separate domains of the molecule.« less

  10. Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny.

    PubMed

    Ling, Binbing; Aziz, Caroline; Wojnarowicz, Chris; Olkowski, Andrew; Alcorn, Jane

    2010-10-14

    Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

  11. Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

    PubMed Central

    Ling, Binbing; Aziz, Caroline; Wojnarowicz, Chris; Olkowski, Andrew; Alcorn, Jane

    2010-01-01

    Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age. PMID:27721360

  12. The Effects of Maternal Postnatal Depression and Child Sex on Academic Performance at Age 16 Years: A Developmental Approach

    ERIC Educational Resources Information Center

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Croudace, Tim; Cooper, Peter

    2010-01-01

    Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long-term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non-depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on…

  13. Effects of acute postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl on sperm function and hormone levels in adult rats.

    PubMed

    Hsu, Ping-Chi; Guo, Yueliang Leon; Li, Mei-Hui

    2004-02-01

    Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.

  14. Understanding exercise self-efficacy and barriers to leisure-time physical activity among postnatal women.

    PubMed

    Cramp, Anita G; Bray, Steven R

    2011-07-01

    Studies have demonstrated that postnatal women are at high risk for physical inactivity and generally show lower levels of leisure-time physical activity (LTPA) compared to prepregnancy. The overall purpose of the current study was to investigate social cognitive correlates of LTPA among postnatal women during a 6-month period following childbirth. A total of 230 women (mean age = 30.9) provided descriptive data regarding barriers to LTPA and completed measures of LTPA and self-efficacy (exercise and barrier) for at least one of the study data collection periods. A total of 1,520 barriers were content analyzed. Both exercise and barrier self-efficacy were positively associated with subsequent LTPA. Exercise self-efficacy at postnatal week 12 predicted LTPA from postnatal weeks 12 to 18 (β = .40, R (2) = .18) and exercise self-efficacy at postnatal week 24 predicted LTPA during weeks 24-30 (β = .49, R (2) = .30). Barrier self-efficacy at week 18 predicted LTPA from weeks 18 to 24 (β = .33, R (2) = .13). The results of the study identify a number of barriers to LTPA at multiple time points closely following childbirth which may hinder initiation, resumption or maintenance of LTPA. The results also suggest that higher levels of exercise and barrier self-efficacy are prospectively associated with higher levels of LTPA in the early postnatal period. Future interventions should be designed to investigate causal effects of developing participants' exercise and barrier self-efficacy for promoting and maintaining LTPA during the postnatal period.

  15. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep.

    PubMed

    Manikkam, Mohan; Crespi, Erica J; Doop, Douglas D; Herkimer, Carol; Lee, James S; Yu, Sunkyung; Brown, Morton B; Foster, Douglas L; Padmanabhan, Vasantha

    2004-02-01

    Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

  16. Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption.

    PubMed

    Perkins, Guy A; Scott, Ray; Perez, Alex; Ellisman, Mark H; Johnson, Jerry E; Fox, Donald A

    2012-01-01

    Postnatal lead exposure produces rod-selective and Bax-mediated apoptosis, decreased scotopic electroretinograms (ERGs), and scotopic and mesopic vision deficits in humans and/or experimental animals. Rod, but not cone, inner segment mitochondria were considered the primary site of action. However, photoreceptor synaptic mitochondria were not examined. Thus, our experiments investigated the structural and functional effects of environmentally relevant postnatal lead exposure on rod spherule and cone pedicle mitochondria and whether Bcl-xL overexpression provided neuroprotection. C57BL/6N mice pups were exposed to lead only during lactation via dams drinking water containing lead acetate. The blood [Pb] at weaning was 20.6±4.7 µg/dl, which decreased to the control value by 2 months. To assess synaptic mitochondrial structural differences and vulnerability to lead exposure, wild-type and transgenic mice overexpressing Bcl-xL in photoreceptors were used. Electron microscopy, three-dimensional electron tomography, and retinal and photoreceptor synaptic terminal oxygen consumption (QO(2)) studies were conducted in adult control, Bcl-xL, lead, and Bcl-xL/lead mice. The spherule and pedicle mitochondria in lead-treated mice were swollen, and the cristae structure was markedly changed. In the lead-treated mice, the mitochondrial cristae surface area and volume (abundance: measure correlated with ATP (ATP) synthesis) were decreased in the spherules and increased in the pedicles. Pedicles also had an increased number of crista segments per volume. In the lead-treated mice, the number of segments/crista and fraction of cristae with multiple segments (branching) similarly increased in spherule and pedicle mitochondria. Lead-induced remodeling of spherule mitochondria produced smaller cristae with more branching, whereas pedicle mitochondria had larger cristae with more branching and increased crista junction (CJ) diameter. Lead decreased dark- and light-adapted photoreceptor

  17. Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

    PubMed

    Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

    2017-11-01

    The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

  18. Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure.

    PubMed

    Grignard, Elise; Guéguen, Yann; Grison, Stéphane; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

    2010-05-01

    The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium ((137)Cs) exposure, the effects of chronic contamination with low doses of (137)Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17beta-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organisms may be affected at the molecular level by (137)Cs contamination at this post-accidental dose. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  19. Early-Life Soy Exposure and Gender-Role Play Behavior in Children

    PubMed Central

    Daniels, Julie L.; Edwards, Lloyd J.; Siega-Riz, Anna Maria; Rogan, Walter J.

    2011-01-01

    Background: Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. Objective: We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. Methods: We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. Results: Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (® = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. Conclusions: Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys. PMID:21813368

  20. Early-life soy exposure and gender-role play behavior in children.

    PubMed

    Adgent, Margaret A; Daniels, Julie L; Edwards, Lloyd J; Siega-Riz, Anna Maria; Rogan, Walter J

    2011-12-01

    Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (β = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys.

  1. Significant calendar period deviations in testicular germ cell tumors indicate that postnatal exposures are etiologically relevant.

    PubMed

    Speaks, Crystal; McGlynn, Katherine A; Cook, Michael B

    2012-10-01

    The current working model of type II testicular germ cell tumor (TGCT) pathogenesis states that carcinoma in situ arises during embryogenesis, is a necessary precursor, and always progresses to cancer. An implicit condition of this model is that only in utero exposures affect the development of TGCT in later life. In an age-period-cohort analysis, this working model contends an absence of calendar period deviations. We tested this contention using data from the SEER registries of the United States. We assessed age-period-cohort models of TGCTs, seminomas, and nonseminomas for the period 1973-2008. Analyses were restricted to whites diagnosed at ages 15-74 years. We tested whether calendar period deviations were significant in TGCT incidence trends adjusted for age deviations and cohort effects. This analysis included 32,250 TGCTs (18,475 seminomas and 13,775 nonseminomas). Seminoma incidence trends have increased with an average annual percentage change in log-linear rates (net drift) of 1.25 %, relative to just 0.14 % for nonseminoma. In more recent time periods, TGCT incidence trends have plateaued and then undergone a slight decrease. Calendar period deviations were highly statistically significant in models of TGCT (p = 1.24(-9)) and seminoma (p = 3.99(-14)), after adjustment for age deviations and cohort effects; results for nonseminoma (p = 0.02) indicated that the effects of calendar period were much more muted. Calendar period deviations play a significant role in incidence trends of TGCT, which indicates that postnatal exposures are etiologically relevant.

  2. Exposure to low doses of 137cesium and nicotine during postnatal development modifies anxiety levels, learning, and spatial memory performance in mice.

    PubMed

    Bellés, Montserrat; Heredia, Luis; Serra, Noemí; Domingo, José L; Linares, Victoria

    2016-11-01

    Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation ( 137 Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium ( 137 Cs) (4000 and 8000 Bq/kg) and/or Nic (100 μg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137 Cs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study

    PubMed Central

    Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

    2015-01-01

    Objective To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Study design Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Results Mean length-for-age z score was −0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m2; 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (−41.5 g per twofold increase in ferritin; 95% CI −78 to −5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of −0.06 per 20 nmol/L; 95% CI −0.11 to −0.01) was observed. Conclusions Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. PMID:25246090

  4. Multimethod Approach to the Early Postnatal Growth of the Mandible in Mice from a Zone of Robertsonian Polymorphism.

    PubMed

    Martínez-Vargas, Jessica; Muñoz-Muñoz, Francesc; López-Fuster, María José; Cubo, Jorge; Ventura, Jacint

    2018-04-18

    The western European house mouse (Mus musculus domesticus) shows high karyotypic diversity owing to Robertsonian translocations. Morphometric studies conducted with adult mice suggest that karyotype evolution due to these chromosomal reorganizations entails variation in the form and the patterns of morphological covariation of the mandible. However, information is much scarcer regarding the effect of these rearrangements on the growth pattern of the mouse mandible over early postnatal ontogeny. Here we compare mandible growth from the second to the eighth week of postnatal life between two ontogenetic series of mice from wild populations, with the standard karyotype and with Robertsonian translocations respectively, reared under the same conditions. A multi-method approach is used, including bone histology analyses of mandible surfaces and cross-sections, as well as geometric morphometric analyses of mandible form. The mandibles of both standard and Robertsonian mice display growth acceleration around weaning, anteroposterior direction of bone maturation, a predominance of bone deposition fields over ontogeny, and relatively greater expansion of the posterior mandible region correlated with the ontogenetic increase in mandible size. Nevertheless, differences exist between the two mouse groups regarding the timing of histological maturation of the mandible, the localization of certain bone remodeling fields, the temporospatial patterns of morphological variation, and the organization into two main modules. The dissimilarities in the process of mandible growth between the two groups of mice become more evident around sexual maturity, and could arise from alterations that Robertsonian translocations may exert on genes involved in the bone remodeling mechanism. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  5. Auditory hindbrain atrophy and anomalous calcium binding protein expression after neonatal exposure to monosodium glutamate.

    PubMed

    Foran, Lindsey; Blackburn, Kaitlyn; Kulesza, Randy J

    2017-03-06

    Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, elevated extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavor enhancer in many processed foods. Previous studies have shown that MSG administration during the early postnatal period results in neurodegenerative changes in several forebrain regions, characterized by neuronal loss and neuroendocrine abnormalities. Systemic delivery of MSG during the neonatal period and induction of glutamate neurotoxicity in the cochlea have both been shown to result in fewer neurons in the spiral ganglion. We hypothesized that an MSG-induced loss of neurons in the spiral ganglion would have a significant impact on the number of neurons in the cochlear nuclei and superior olivary complex (SOC). Indeed, we found that exposure to MSG from postnatal days 4 through 10 resulted in significantly fewer neurons in the cochlear nuclei and SOC and significant dysmorphology in surviving neurons. Moreover, we found that neonatal MSG exposure resulted in a significant decrease in the expression of both calretinin and calbindin. These results suggest that neonatal exposure to MSG interferes with early development of the auditory brainstem and impacts expression of calcium binding proteins, both of which may lead to diminished auditory function. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  7. Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.

    PubMed

    Paul, Katie B; Hedge, Joan M; Bansal, Ruby; Zoeller, R Thomas; Peter, Robert; DeVito, Michael J; Crofton, Kevin M

    2012-10-09

    This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the

  8. Increased Excitatory Synaptic Transmission of Dentate Granule Neurons in Mice Lacking PSD-95-Interacting Adhesion Molecule Neph2/Kirrel3 during the Early Postnatal Period.

    PubMed

    Roh, Junyeop D; Choi, Su-Yeon; Cho, Yi Sul; Choi, Tae-Yong; Park, Jong-Sil; Cutforth, Tyler; Chung, Woosuk; Park, Hanwool; Lee, Dongsoo; Kim, Myeong-Heui; Lee, Yeunkum; Mo, Seojung; Rhee, Jeong-Seop; Kim, Hyun; Ko, Jaewon; Choi, Se-Young; Bae, Yong Chul; Shen, Kang; Kim, Eunjoon; Han, Kihoon

    2017-01-01

    Copy number variants and point mutations of NEPH2 (also called KIRREL3 ) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2 -/- mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2 -/- mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations.

  9. Is the organisation and structure of hospital postnatal care a barrier to quality care? Findings from a state-wide review in Victoria, Australia.

    PubMed

    McLachlan, Helen L; Forster, Della A; Yelland, Jane; Rayner, Joanne; Lumley, Judith

    2008-09-01

    to describe the structure and organisation of hospital postnatal care in Victoria, Australia. postal survey sent to all public hospitals in Victoria (n=71) and key-informant interviews with midwives and medical practitioners (n=38). Victoria, Australia. providers of postnatal care in Victorian public hospitals. there is significant diversity across Victoria in the way postnatal units are structured and organised and in the way care is provided. There are differences in numerous practices, including maternal and neonatal observations and the length of time women spend in hospital after giving birth. Although the benefits of continuity of care are recognised by health care providers, continuity is difficult to provide in the postnatal period. Postnatal care is provided in busy, sometimes chaotic environments, with many barriers to providing effective care and few opportunities for women to rest and recover after childbirth. The findings in this study can, in part, be explained by the lack of evidence that has been available to guide early postnatal care. current structures such as standard postnatal documentation (clinical pathways) and fixed length of stay, may inhibit rather than support individualised care for women after childbirth. There is a need to move towards greater flexibility in providing of early postnatal care, including alternative models of service delivery; choice and flexibility in the length of stay after birth; a focus on the individual with far less emphasis on care being structured around organisational requirements; and building an evidence base to guide care.

  10. Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

    PubMed Central

    Girard, Beatrice; Peterson, Abbey; Malley, Susan; Vizzard, Margaret A.

    2016-01-01

    The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, continuous fill, conscious cystometry; (2) innervation and neurochemical coding of the suburothelial plexus of the urinary bladder using immunohistochemistry and semi-quantitative image analyses; (3) neuropeptide protein and transcript expression in urinary bladder of postnatal and adult NGF-OE mice using Q-PCR and ELISAs and (4) the effects of intravesical instillation of a neurokinin (NK)-1 receptor antagonist on bladder function in postnatal and adult NGF-OE mice using conscious cystometry. Postnatal NGF-OE mice exhibit age-dependent (R2= 0.996–0.998; p ≤ 0.01) increases in Sub and CGRP expression in the urothelium and significantly (p ≤ 0.01) increased peptidergic hyperinnervation of the suburothelial nerve plexus. By as early as P7, NGF-OE mice exhibit a vesicovesical reflex in response to intravesical instillation of saline whereas littermate WT mice require perigenital stimulation to elicit a micturition reflex until P13 when vesicovesical reflexes are first observed. Intravesical instillation of a NK-1 receptor antagonist, netupitant (0.1 μg/ml), significantly (p ≤ 0.01) increased void volume and the interval between micturition events with no effects on bladder pressure (baseline, threshold, peak) in postnatal NGF-OE mice; effects on WT mice were few. NGF-induced pleiotropic effects on neuropeptide (e.g., Sub P) expression in the urinary bladder

  11. Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis.

    PubMed

    Rochester, Johanna R; Bolden, Ashley L; Kwiatkowski, Carol F

    2018-05-01

    Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans. Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD. Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017. For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3 months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring. Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20 μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model. A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls. We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include

  12. Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

    PubMed Central

    Indrio, Flavia; Martini, Silvia; Francavilla, Ruggiero; Corvaglia, Luigi; Cristofori, Fernanda; Mastrolia, Salvatore Andrea; Neu, Josef; Rautava, Samuli; Russo Spena, Giovanna; Raimondi, Francesco; Loverro, Giuseppe

    2017-01-01

    Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects. PMID:28879172

  13. Postnatal aniracetam treatment improves prenatal ethanol induced attenuation of AMPA receptor-mediated synaptic transmission.

    PubMed

    Wijayawardhane, Nayana; Shonesy, Brian C; Vaglenova, Julia; Vaithianathan, Thirumalini; Carpenter, Mark; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu

    2007-06-01

    Aniracetam is a nootropic compound and an allosteric modulator of AMPA receptors (AMPARs) which mediate synaptic mechanisms of learning and memory. Here we analyzed impairments in AMPAR-mediated synaptic transmission caused by moderate prenatal ethanol exposure and investigated the effects of postnatal aniracetam treatment on these abnormalities. Pregnant Sprague-Dawley rats were gavaged with ethanol or isocaloric sucrose throughout pregnancy, and subsequently the offspring were treated with aniracetam on postnatal days (PND) 18 to 27. Hippocampal slices prepared from these pups on PND 28 to 34 were used for the whole-cell patch-clamp recordings of AMPAR-mediated spontaneous and miniature excitatory postsynaptic currents in CA1 pyramidal cells. Our results indicate that moderate ethanol exposure during pregnancy results in impaired hippocampal AMPAR-mediated neurotransmission, and critically timed aniracetam treatment can abrogate this deficiency. These results highlight the possibility that aniracetam treatment can restore synaptic transmission and ameliorate cognitive deficits associated with the fetal alcohol syndrome.

  14. In utero and acute exposure to benzene: investigation of DNA double-strand breaks and DNA recombination in mice.

    PubMed

    Lau, Annette; Belanger, Christine Lea; Winn, Louise M

    2009-05-31

    Benzene, a ubiquitous pollutant, has been identified as a human leukemogen and early exposure to environmental carcinogens such as benzene has been linked to childhood leukemia. It is known that genotoxic agents can increase the frequency of DNA double-strand breaks (DSBs), which can initiate DNA recombinational repair mechanisms. In this study we investigated the induction of micronuclei, the formation of gamma-H2A.X as a marker of DNA DSBs, and the induction of somatic DNA recombination events in hematopoietic tissue from pKZ1 transgenic mice exposed acutely or in utero to benzene. Adult male C57Bl/6N mice were treated with a single i.p. injection of benzene, and timed-pregnant females pKZ1 were treated with daily i.p. injections of 200 mg/kg or 400 mg/kg benzene through gestational days 7-15. Acute exposure to 400 mg/kg benzene resulted in a statistically significant increase in the percentage of micronucleated cells in adult male bone marrow cells and in fetal liver and post-natal day 9 bone marrow cells of mice exposed in utero. Immunoblotting techniques did not detect benzene-induced increases in the formation of gamma-H2A.X in bone marrow cells of adult male mice and in maternal bone marrow, fetal liver, and post-natal bone marrow cells after specific time-point exposures. Finally, no recombination events were detected in adult pKZ1 mouse tissue; however, in post-natal day 9 pups in utero exposure to 400 mg/kg of benzene caused a trend towards increasing recombination frequency although this did not reach statistical significance. These results demonstrate that in utero exposure increases the frequency of micronuclei and DNA recombination events in hematopoietic tissue of fetal and post-natal mice and may be an initiating event in the etiology of childhood leukemias. Further investigations into different types of DNA damage and repair pathways are warranted to fully elucidate the role of genotoxic mechanisms in the etiology of benzene-induced childhood

  15. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    PubMed

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  16. Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children.

    PubMed

    Wen, D J; Poh, J S; Ni, S N; Chong, Y-S; Chen, H; Kwek, K; Shek, L P; Gluckman, P D; Fortier, M V; Meaney, M J; Qiu, A

    2017-04-25

    Maternal depressive symptoms influence neurodevelopment in the offspring. Such effects may appear to be gender-dependent. The present study examined contributions of prenatal and postnatal maternal depressive symptoms to the volume and microstructure of the amygdala in 4.5-year-old boys and girls. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression was assessed at 3 months using the EPDS and at 1, 2, 3 and 4.5 years using the Beck's Depression Inventory-II. Structural magnetic resonance imaging and diffusion tensor imaging were performed with 4.5-year-old children to extract the volume and fractional anisotropy (FA) values of the amygdala. Our results showed that greater prenatal maternal depressive symptoms were associated with larger right amygdala volume in girls, but not in boys. Increased postnatal maternal depressive symptoms were associated with higher right amygdala FA in the overall sample and girls, but not in boys. These results support the role of variation in right amygdala structure in transmission of maternal depression to the offspring, particularly to girls. The differential effects of prenatal and postnatal maternal depressive symptoms on the volume and FA of the right amygdala suggest the importance of the timing of exposure to maternal depressive symptoms in brain development of girls. This further underscores the need for intervention targeting both prenatal and postnatal maternal depression to girls in preventing adverse child outcomes.

  17. Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children

    PubMed Central

    Wen, D J; Poh, J S; Ni, S N; Chong, Y-S; Chen, H; Kwek, K; Shek, L P; Gluckman, P D; Fortier, M V; Meaney, M J; Qiu, A

    2017-01-01

    Maternal depressive symptoms influence neurodevelopment in the offspring. Such effects may appear to be gender-dependent. The present study examined contributions of prenatal and postnatal maternal depressive symptoms to the volume and microstructure of the amygdala in 4.5-year-old boys and girls. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression was assessed at 3 months using the EPDS and at 1, 2, 3 and 4.5 years using the Beck's Depression Inventory-II. Structural magnetic resonance imaging and diffusion tensor imaging were performed with 4.5-year-old children to extract the volume and fractional anisotropy (FA) values of the amygdala. Our results showed that greater prenatal maternal depressive symptoms were associated with larger right amygdala volume in girls, but not in boys. Increased postnatal maternal depressive symptoms were associated with higher right amygdala FA in the overall sample and girls, but not in boys. These results support the role of variation in right amygdala structure in transmission of maternal depression to the offspring, particularly to girls. The differential effects of prenatal and postnatal maternal depressive symptoms on the volume and FA of the right amygdala suggest the importance of the timing of exposure to maternal depressive symptoms in brain development of girls. This further underscores the need for intervention targeting both prenatal and postnatal maternal depression to girls in preventing adverse child outcomes. PMID:28440816

  18. Neural stem cell apoptosis after low-methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits.

    PubMed

    Sokolowski, Katie; Obiorah, Maryann; Robinson, Kelsey; McCandlish, Elizabeth; Buckley, Brian; DiCicco-Bloom, Emanuel

    2013-12-01

    The developing brain is particularly sensitive to exposures to environmental contaminants. In contrast to the adult, the developing brain contains large numbers of dividing neuronal precursors, suggesting that they may be vulnerable targets. The postnatal day 7 (P7) rat hippocampus has populations of both mature neurons in the CA1-3 region as well as neural stem cells (NSC) in the dentate gyrus (DG) hilus, which actively produce new neurons that migrate to the granule cell layer (GCL). Using this well-characterized NSC population, we examined the impact of low levels of methylmercury (MeHg) on proliferation, neurogenesis, and subsequent adolescent learning and memory behavior. Assessing a range of exposures, we found that a single subcutaneous injection of 0.6 µg/g MeHg in P7 rats induced caspase activation in proliferating NSC of the hilus and GCL. This acute NSC death had lasting impact on the DG at P21, reducing cell numbers in the hilus by 22% and the GCL by 27%, as well as reductions in neural precursor proliferation by 25%. In contrast, non-proliferative CA1-3 pyramidal neuron cell number was unchanged. Furthermore, animals exposed to P7 MeHg exhibited an adolescent spatial memory deficit as assessed by Morris water maze. These results suggest that environmentally relevant levels of MeHg exposure may decrease NSC populations and, despite ongoing neurogenesis, the brain may not restore the hippocampal cell deficits, which may contribute to hippocampal-dependent memory deficits during adolescence. Copyright © 2013 Wiley Periodicals, Inc.

  19. A qualitative study of the acceptability of routine screening of postnatal women using the Edinburgh Postnatal Depression Scale.

    PubMed Central

    Shakespeare, Judy; Blake, Fiona; Garcia, Jo

    2003-01-01

    BACKGROUND: Screening for postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) has been widely recommended and implemented in primary care, although little is known about how acceptable it is to women. AIM: To explore the acceptability to women of postnatal screening by health visitors with the EPDS. DESIGN OF STUDY: Qualitative interview study. SETTING: Postnatal patients from 22 general practices within the area of Oxford City Primary Care Group. METHOD: Thirty-nine postnatal women from a purposive sample were interviewed, chosen on the basis of different general practices, EPDS results at eight weeks and eight months postnatal, and whether 'listening visits' were received. The interviews were analysed using the constant comparative method. RESULTS: Just over half of the women interviewed found screening with the EPDS less than acceptable, whatever their postnatal emotional health. The main themes identified were problems with the process of screening and, in particular, the venue, the personal intrusion of screening and stigma. The women interviewed had a clear preference for talking about how they felt, rather than filling out a questionnaire. CONCLUSION: For this sample, routine screening with the EPDS was less than acceptable for the majority of women. This is of concern, as universal screening with the EPDS for the detection of postnatal depression is already recommended and widespread in primary care. PMID:14601337

  20. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    PubMed

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

  1. Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression

    PubMed Central

    Saravia, Jordy; You, Dahui; Thevenot, Paul; Lee, Greg I.; Shrestha, Bishwas; Lomnicki, Slawo; Cormier, Stephania A.

    2013-01-01

    Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyperresponsiveness, Th2-inflammation, Muc5ac expression, eosinophilia, and HDM-specific Ig compared to HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was two-fold higher in CDPM+HDM mice compared to HDM-mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and Tregs, resulting in suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific-antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life. PMID:24172848

  2. Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

    PubMed Central

    Gilbert, Kathleen M.; Woodruff, William; Blossom, Sarah J.

    2014-01-01

    Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences. PMID:24696780

  3. Early exposure of rotating magnetic fields promotes central nervous regeneration in planarian Girardia sinensis.

    PubMed

    Chen, Qiang; Lin, Gui-miao; Wu, Nan; Tang, Sheng-wei; Zheng, Zhi-jia; Lin, Marie Chia-mi; Xu, Gai-xia; Liu, Hao; Deng, Yue-yue; Zhang, Xiao-yun; Chen, Si-ping; Wang, Xiao-mei; Niu, Han-ben

    2016-05-01

    Magnetic field exposure is an accepted safe and effective modality for nerve injury. However, it is clinically used only as a supplement or salvage therapy at the later stage of treatment. Here, we used a planarian Girardia sinensis decapitated model to investigate beneficial effects of early rotary non-uniform magnetic fields (RMFs) exposure on central nervous regeneration. Our results clearly indicated that magnetic stimulation induced from early RMFs exposure significantly promoted neural regeneration of planarians. This stimulating effect is frequency and intensity dependent. Optimum effects were obtained when decapitated planarians were cultured at 20 °C, starved for 3 days before head-cutting, and treated with 6 Hz 0.02 T RMFs. At early regeneration stage, RMFs exposure eliminated edema around the wound and facilitated subsequent formation of blastema. It also accelerated cell proliferation and recovery of neuron functionality. Early RMFs exposure up-regulated expression of neural regeneration related proteins, EGR4 and Netrin 2, and mature nerve cell marker proteins, NSE and NPY. These results suggest that RMFs therapy produced early and significant benefit in central nervous regeneration, and should be clinically used at the early stage of neural regeneration, with appropriate optimal frequency and intensity. © 2016 Wiley Periodicals, Inc.

  4. Dog and cat exposure and respective pet allergy in early childhood.

    PubMed

    Pyrhönen, Kaisa; Näyhä, Simo; Läärä, Esa

    2015-05-01

    The association of dog and cat exposure in early childhood with the incidence of respective allergies has remained controversial. The aim of the study was to obtain population-based evidence on the association of early exposure to dog or cat, or both, with dog and cat allergies. The study population was identified from the nationwide population register comprising all children aged 1-4 yr (N = 4779) born between 2001 and 2005 and living in the province of South Karelia, Finland. Cross-sectional questionnaire data on pet exposure in infancy and physician-diagnosed pet allergies were obtained from 3024 participants and merged with longitudinally accumulated data on sIgE and skin prick tests indicating allergic sensitization abstracted from all patient records in the area. The adjusted relative incidence of positive test results (with 95% confidence intervals) was 2.69 (1.45-5.02) for dog and 5.03 (2.47-10.2) for cat allergens among children exposed to a respective pet alone compared with children without such exposure. The corresponding adjusted prevalence odds ratios for diagnosed dog and cat allergies were 1.75 (0.77-3.79) and 5.13 (2.30-11.4), respectively. The association between pet exposure and the incidence of positive test results was independent of parents' allergies. Early exposure to dog and cat at home is associated with a higher incidence of respective pet allergy during the first four years of life. Further evidence from population-based studies with longer follow-up is required to justify any recommendation concerning early pet contacts with a view to preventing pet allergies later in life. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Neurobiology and neurodevelopmental impact of childhood traumatic stress and prenatal alcohol exposure.

    PubMed

    Henry, Jim; Sloane, Mark; Black-Pond, Connie

    2007-04-01

    Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic experience alone. Although the harmful effects of both have been well documented individually, there is no research documenting the concurrent effects of prenatal alcohol exposure and postnatal trauma on a child's developmental process. Transdisciplinary assessment of the children included the core disciplines of medicine, speech-language pathology, occupational therapy, social work, and psychology. Medical examination, standardized developmental and intelligence testing, projective tools, parent questionnaires, and psychosocial interviews provided information in the primary developmental areas. Findings indicated that children who had been exposed prenatally to alcohol along with postnatal traumatic experience had lower intelligence scores and more severe neurodevelopmental deficits in language, memory, visual processing, motor skills, and attention than did traumatized children without prenatal alcohol exposure, as well as greater oppositional/defiant behavior, inattention, hyperactivity, impulsivity, and social problems. Successful teacher and speech-language pathologist interventions with traumatized children with prenatal alcohol exposure demand a paradigm shift that requires the development of new perspectives and ongoing training.

  6. Identification of depression in women during pregnancy and the early postnatal period using the Whooley questions and the Edinburgh Postnatal Depression Scale: protocol for the Born and Bred in Yorkshire: PeriNatal Depression Diagnostic Accuracy (BaBY PaNDA) study.

    PubMed

    Littlewood, Elizabeth; Ali, Shehzad; Ansell, Pat; Dyson, Lisa; Gascoyne, Samantha; Hewitt, Catherine; Keding, Ada; Mann, Rachel; McMillan, Dean; Morgan, Deborah; Swan, Kelly; Waterhouse, Bev; Gilbody, Simon

    2016-06-13

    Perinatal depression is well recognised as a mental health condition but <50% of cases are identified by healthcare professionals in routine clinical practice. The Edinburgh Postnatal Depression Scale (EPDS) is often used to detect symptoms of postnatal depression in maternity and child services. The National Institute for Health and Care Excellence (NICE) recommends 2 'ultra-brief' case-finding questions (the Whooley questions) to aid identification of depression during the perinatal period, but this recommendation was made in the absence of any validation studies in a perinatal population. Limited research exists on the acceptability of these depression case-finding instruments and the cost-effectiveness of routine screening for perinatal depression. The diagnostic accuracy of the Whooley questions and the EPDS will be determined against a reference standard (the Client Interview Schedule-Revised) during pregnancy (around 20 weeks) and the early postnatal period (around 3-4 months post partum) in a sample of 379 women. Further outcome measures will assess a range of psychological comorbidities, health-related quality of life and resource utilisation. Women will be followed up 12 months postnatally. The sensitivity, specificity and predictive values of the Whooley questions and the EPDS will be calculated against the reference standard at 20 weeks pregnancy and 3-4 months post partum. Acceptability of the depression case-finding instruments to women and healthcare professionals will involve in-depth qualitative interviews. An existing decision analytic model will be adapted to determine the cost-effectiveness of routine screening for perinatal depression. This study is considered low risk for participants. Robust protocols will deal with cases where risk of depression, self-harm or suicide is identified. The protocol received favourable ethical opinion from the North East-York Research Ethics Committee (reference: 11/NE/0022). The study findings will be

  7. Children's Prenatal Exposure to Drugs: Implications for Early Childhood Educators.

    ERIC Educational Resources Information Center

    Mayfield, Phyllis K.; Chapman, J. Keith

    1998-01-01

    Examines the effects of drug use during pregnancy on early and later child development, the extent of women's drug use, and behavioral and learning characteristics of children prenatally exposed to drugs. Provides intervention guidelines for early childhood settings including children with prenatal drug exposure, focusing on recommendations for…

  8. Acute in utero exposure to lipopolysaccharide induces inflammation in the pre- and postnatal brain and alters the glial cytoarchitecture in the developing amygdala.

    PubMed

    O'Loughlin, Elaine; Pakan, Janelle M P; Yilmazer-Hanke, Deniz; McDermott, Kieran W

    2017-11-02

    Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism and schizophrenia, as well as seizure development. The amygdala is a brain region involved in the regulation of emotions, and amygdalar maldevelopment due to infection-induced MIA may lead to amygdala-related disorders. MIA priming of glial cells during development has been linked to abnormalities seen in later life; however, little is known about its effects on amygdalar biochemical and cytoarchitecture integrity. Time-mated C57BL6J mice were administered a single intraperitoneal injection of 50 μg/kg lipopolysaccharide (LPS) on embryonic day 12 (E12), and the effects of MIA were examined at prenatal, neonatal, and postnatal developmental stages using immunohistochemistry, real-time quantitative PCR, and stereological quantification of cytoarchitecture changes. Fetal brain expression of pro-inflammatory cytokines (IL-1β, TNFα, and IL-6) was significantly upregulated at 4 h postinjection (E12) and remained elevated until the day of birth (P0). In offspring from LPS-treated dams, amygdalar expression of pro-inflammatory cytokines was also increased on day 7 (P7) and expression was sustained on day 40 (P40). Toll-like receptor (TLR-2, TLR-4) expression was also upregulated in fetal brains and in the postnatal amygdala in LPS-injected animals. Morphological examination of cells expressing ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) suggested long-term microglial activation and astrogliosis in postnatal amygdalar regions. Our results showed that LPS-induced MIA at E12 induces a pro-inflammatory cytokine profile in the developing fetal brain that continues up to early adulthood in the amygdala. Inflammation elicited by MIA may activate cells in the fetal brain and lead to alterations in glial (microglia and astrocyte) cells observed in the postnatal amygdala. Moreover, increased pro-inflammatory cytokines and their

  9. Fish consumption, mercury exposure, and their associations with scholastic achievement in the Seychelles Child Development Study.

    PubMed

    Davidson, Philip W; Leste, Andre; Benstrong, Egbert; Burns, Christine M; Valentin, Justin; Sloane-Reeves, Jean; Huang, Li-Shan; Miller, Wesley A; Gunzler, Douglas; van Wijngaarden, Edwin; Watson, Gene E; Zareba, Grazyna; Shamlaye, Conrad F; Myers, Gary J

    2010-09-01

    Studies of neurodevelopmental outcomes in offspring exposed to MeHg from maternal consumption of fish have primarily measured cognitive abilities. Reported associations have been subtle and in both adverse and beneficial directions. Changes in functional outcomes such as school achievement and behavior in exposed children and adolescents have not been examined. We undertook an assessment of school success of children in the Seychelles Child Development Study (SCDS) main cohort to determine if there were any associations with either prenatal or recent postnatal MeHg exposure. The primary endpoints were Seychelles nationally standardized end-of-year examinations given when the cohort children were 9 and 17 years of age. A subgroup (n=215) from the main cohort was also examined at 9 years of age using a regional achievement test called SACMEQ. Prenatal MeHg exposure was 6.8 ppm in maternal hair; recent postnatal exposure was 6.09 ppm at 9 years and 8.0 ppm at 17 years, measured in child hair. Multiple linear regression analyses showed no pattern of associations between prenatal or postnatal exposure, and either the 9- or 17-year end-of-year examination scores. For the subgroup of 215 subjects who participated in the SACMEQ test, there were significant adverse associations between examination scores and postnatal exposure, but only for males. The average postnatal exposure level in child hair for this subgroup was significantly higher than for the overall cohort. These results are consistent with our earlier studies and support the interpretation that prenatal MeHg exposure at dosages achieved by mothers consuming a diet high in fish are not associated with adverse educational measures of scholastic achievement. The adverse association of educational measures with postnatal exposure in males is intriguing, but will need to be confirmed by further studies examining factors that influence scholastic achievement. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Fish consumption in pregnancy and omega-3 status after birth are not associated with postnatal depression.

    PubMed

    Browne, Joanna C; Scott, Kate M; Silvers, Karen M

    2006-02-01

    Research to date suggests a relationship between fish consumption, omega-3 polyunsaturated fatty acids, and depression. However, interpretation of this research is difficult due to methodological limitations. Postpartum women provide an excellent opportunity to examine these relationships because omega-3s are transferred from mother to fetus during pregnancy and from mother to child after birth through breast milk. Hence new mothers are more likely to be depleted in omega-3s. Our aim was to determine whether prenatal fish consumption and omega-3 status after birth were associated with postnatal depression. Eighty first-time mothers were recruited; 41 who scored on or over the cut-off on one of two depression-screening instruments, and 39 in the control group. Depression was diagnosed using the Composite International Diagnostic Interview. Fish consumption was measured during pregnancy, and depression and omega-3 status were determined postnatally. Logistic regression and t-tests were used to examine relationships between fish consumption, omega-3 status, and postnatal depression, while controlling for known covariates. Prenatal fish consumption was not predictive of postnatal depression, and postnatal omega-3 status was not associated with postnatal depression. However, prenatal fish consumption did predict omega-3 status after birth. Prenatal fish consumption was measured using only a food frequency questionnaire, and no participants consumed oily fish (rich in omega-3s) regularly. There was no association between postnatal depression and either fish consumption in early pregnancy, or omega-3 status after birth. Our findings make it difficult to justify trials of omega-3 polyunsaturated fatty acids in the treatment of postnatal depression.

  11. Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats.

    PubMed

    Ji, Chenlin; Dai, Yanyan; Jiang, Weiwei; Liu, Juan; Hou, Miao; Wang, Junle; Burén, Jonas; Li, Xiaonan

    2014-11-01

    Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Long-Term Neurotoxic Effects of Early Life Exposure to Tetrachloroethylene-contaminated Drinking Water

    PubMed Central

    Aschengrau, Ann; Janulewicz, Patricia A.; White, Roberta F.; Vieira, Veronica M.; Gallagher, Lisa G.; Getz, Kelly D.; Webster, Thomas F.; Ozonoff, David M.

    2016-01-01

    Background Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983 widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. Objectives A retrospective cohort study (“the Cape Cod Health Study”) was undertaken to examine possible health consequences of early life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the impact of prenatal and childhood exposure on neurological outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiological research in this unique setting. Methods Subjects were identified by cross-matching birth certificate and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (N= 1,689), neuropsychological tests (N=63), vision exam (N=63), and magnetic resonance imaging (N=42). Early life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among subjects with prenatal and early childhood PCE exposure to unexposed subjects while considering the impact of confounding variables. Results The study found evidence that early life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from

  13. Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

    PubMed

    Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

    2014-02-01

    Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

  14. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  15. Temporary Depletion of Microglia during the Early Postnatal Period Induces Lasting Sex-Dependent and Sex-Independent Effects on Behavior in Rats

    PubMed Central

    2016-01-01

    Abstract Microglia are the primary immune cells of the brain and function in multiple ways to facilitate proper brain development. However, our current understanding of how these cells influence the later expression of normal behaviors is lacking. Using the laboratory rat, we administered liposomal clodronate centrally to selectively deplete microglia in the developing postnatal brain. We then assessed a range of developmental, juvenile, and adult behaviors. Liposomal clodronate treatment on postnatal days 0, 2, and 4 depleted microglia with recovery by about 10 days of age and induced a hyperlocomotive phenotype, observable in the second postnatal week. Temporary microglia depletion also increased juvenile locomotion in the open field test and decreased anxiety-like behaviors in the open field and elevated plus maze. These same rats displayed reductions in predator odor–induced avoidance behavior, but increased their risk assessment behaviors compared with vehicle-treated controls. In adulthood, postnatal microglia depletion resulted in significant deficits in male-specific sex behaviors. Using factor analysis, we identified two underlying traits—behavioral disinhibition and locomotion—as being significantly altered by postnatal microglia depletion. These findings further implicate microglia as being critically important to the development of juvenile and adult behavior. PMID:27957532

  16. Early alcohol exposure impairs ocular dominance plasticity throughout the critical period.

    PubMed

    Medina, Alexandre E; Ramoa, Ary S

    2005-06-09

    Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

  17. Early adolescent exposure to alcohol advertising and its relationship to underage drinking.

    PubMed

    Collins, Rebecca L; Ellickson, Phyllis L; McCaffrey, Daniel; Hambarsoomians, Katrin

    2007-06-01

    To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Two in-school surveys of 1786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during 6th grade, and drinking intentions and behavior at 7th grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. After adjusting for covariates, the joint effect of exposure to advertising from all six sources at grade 6 was strongly predictive of grade 7 drinking and grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence.

  18. Early Embryonic Androgen Exposure Induces Transgenerational Epigenetic and Metabolic Changes

    PubMed Central

    Xu, Ning; Chua, Angela K.; Jiang, Hong; Liu, Ning-Ai

    2014-01-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study. PMID:24992182

  19. Genetic control of postnatal human brain growth

    PubMed Central

    van Dyck, Laura I.; Morrow, Eric M.

    2017-01-01

    Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

  20. Major epigenetic development distinguishing neuronal and non-neuronal cells occurs postnatally in the murine hypothalamus

    USDA-ARS?s Scientific Manuscript database

    Prenatal and early postnatal environment can persistently alter one's risk of obesity. Environmental effects on hypothalamic developmental epigenetics constitute a likely mechanism underlying such 'developmental programming' of energy balance regulation. To advance our understanding of these process...

  1. Early life exposure to ambient air pollution and childhood asthma in China.

    PubMed

    Deng, Qihong; Lu, Chan; Norbäck, Dan; Bornehag, Carl-Gustaf; Zhang, Yinping; Liu, Weiwei; Yuan, Hong; Sundell, Jan

    2015-11-01

    Early life is suggested to be a critical time in determining subsequent asthma development, but the extent to which the effect of early-life exposure to ambient air pollution on childhood asthma is unclear. We investigated doctor-diagnosed asthma in preschool children due to exposure to ambient air pollution in utero and during the first year of life. In total 2490 children aged 3-6 years participated in a questionnaire study regarding doctor-diagnosed asthma between September 2011 and January 2012 in China. Children's exposure to critical air pollutants, sulfur dioxide (SO2) as proxy of industrial air pollution, nitrogen dioxide (NO2) as proxy of traffic pollution, and particulate matter≤10µm in diameter (PM10) as a mixture, was estimated from the concentrations measured at the ambient air quality monitoring stations by using an inverse distance weighted (IDW) method. Logistic regression analysis was employed to determine the relationship between early-life exposure and childhood asthma in terms of odds ratio (OR) and 95% confidence interval (CI). Association between early-life exposure to air pollutants and childhood asthma was observed. SO2 and NO2 had significant associations with adjusted OR (95% CI) of 1.45 (1.02-2.07) and 1.74 (1.15-2.62) in utero and 1.62 (1.01-2.60) and 1.90 (1.20-3.00) during the first year for per 50 µg/m(3) and 15 µg/m(3) increase respectively. Exposure to the combined high level of SO2 and NO2 in China significantly elevated the asthmatic risk with adjusted OR (95% CI) of 1.76 (1.18-2.64) in utero and 1.85 (1.22-2.79) during the first year compared to the low level exposure. The associations were higher for males and the younger children aged 3-4 than females and the older children aged 5-6. Early-life exposure to ambient air pollution is associated with childhood asthma during which the level and source of air pollution play important roles. The high level and nature of combined industrial and traffic air pollution in China may

  2. Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice

    EPA Science Inventory

    AbstractEnvironmental exposures occurring early in life may have an important influence on cancer risk later in life. Here we investigated carryover effects of young-adult exposure to dichloroacetic acid (DCA), a small molecule analog of pyruvate and low-level environmental cont...

  3. [Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection].

    PubMed

    Alarcón Allen, A; Baquero-Artigao, F

    2011-01-01

    Postnatal cytomegalovirus (CMV) infection in the newborn can occur from exposure to maternal cervical secretions during birth, ingestion of breast milk, transfusion of blood products or transmission by body fluids of infected people. Breast milk is the main source of infection, given the high rate of CMV-positive mothers excreting CMV in milk. Freezing reduces the risk of CMV transmission by breastfeeding, although it does not eliminate it completely. Pasteurisation prevents such transmission, but it can alter the immunological properties of breast milk. Postnatal CMV infection is usually asymptomatic, as it normally results from viral reactivation in the mother, and the neonate is born with protective antibodies. However, in the very low birth weight premature infant the amount of transferred antibodies is smaller and a symptomatic infection can occur. Symptomatic post-natal CMV infection in the newborn typically causes hepatitis, neutropenia, thrombocytopenia or sepsis-like syndrome. Pneumonitis and enteritis are less common, but very characteristic. Diagnosis is based on urine virus detection at the time of onset of symptoms. Postnatal CMV infection in the newborn generally resolves spontaneously without antiviral treatment. Ganciclovir should be reserved for severe cases. Unlike congenital CMV disease, post-natal CMV infection in the preterm infant does not seem to be associated with hearing loss or abnormal neuro-development in long term follow-up. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Cognitive style, personality and vulnerability to postnatal depression.

    PubMed

    Jones, Lisa; Scott, Jan; Cooper, Caroline; Forty, Liz; Smith, Katherine Gordon; Sham, Pak; Farmer, Anne; McGuffin, Peter; Craddock, Nick; Jones, Ian

    2010-03-01

    Only some women with recurrent major depressive disorder experience postnatal episodes. Personality and/or cognitive styles might increase the likelihood of experiencing postnatal depression. To establish whether personality and cognitive style predicts vulnerability to postnatal episodes over and above their known relationship to depression in general. We compared personality and cognitive style in women with recurrent major depressive disorder who had experienced one or more postnatal episodes (postnatal depression (PND) group, n=143) with healthy female controls (control group, n=173). We also examined parous women with recurrent major depressive disorder who experienced no perinatal episodes (non-postnatal depression (NPND) group, n=131). The PND group had higher levels of neuroticism and dysfunctional beliefs, and lower self-esteem than the control group. However, there were no significant differences between the PND and NPND groups. Established personality and cognitive vulnerabilities for depression were reported by women with a history of postnatal depression, but there was no evidence that any of these traits or styles confer a specific risk for the postnatal onset of episodes.

  5. Fish Consumption, Mercury Exposure, and Their Associations with Scholastic Achievement in the Seychelles Child Development Study1

    PubMed Central

    Davidson, Philip W.; Leste, Andre; Benstrong, Egbert; Burns, Christine M.; Valentin, Justin; Sloane-Reeves, Jean; Huang, Li-Shan; Miller, Wesley A.; Gunzler, Douglas; van Wijngaarden, Edwin; Watson, Gene E.; Zareba, Grazyna; Shamlaye, Conrad F.; Myers, Gary J.

    2010-01-01

    Studies of neurodevelopmental outcomes in offspring exposed to MeHg from maternal consumption of fish have primarily measured cognitive abilities. Reported associations have been subtle and in both adverse and beneficial directions. Changes in functional outcomes such as school achievement and behavior in exposed children and adolescents have not been examined. We undertook an assessment of school success of children in the Seychelles Child Development Study (SCDS) Main Cohort to determine if there were any associations with either prenatal or recent postnatal MeHg exposure. The primary endpoints were Seychelles nationally standardized end-of-year examinations given when the cohort children were 9 and 17 years of age. A subgroup (n = 215) from the Main Cohort was also examined at 9 years of age using a regional achievement test called SACMEQ. Prenatal MeHg exposure was 6.8 ppm in maternal hair; recent postnatal exposure was 6.09 ppm at 9 years and 8.0 ppm at 17 years, measured in child hair. Multiple linear regression analyses showed no pattern of associations between prenatal or postnatal exposure, and either the 9- or 17-year end-of-year examination scores. For the subgroup of 215 subjects who participated in the SACMEQ test, there were significant adverse associations between examination scores and postnatal exposure, but only for males. The average postnatal exposure level in child hair for this subgroup was significantly higher than for the overall cohort. These results are consistent with our earlier studies and support the interpretation that prenatal MeHg exposure at dosages achieved by mothers consuming a diet high in fish are not associated with adverse educational measures of scholastic achievement. The adverse association of educational measures with postnatal exposure in males is intriguing, but will need to be confirmed by further studies examining factors that influence scholastic achievement. PMID:20576509

  6. Postnatal Weight Gain Modifies Severity and Functional Outcome of Oxygen-Induced Proliferative Retinopathy

    PubMed Central

    Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R.; Krah, Nathan M.; Dennison, Roberta J.; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D.; Smith, Lois E.H.

    2010-01-01

    In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r2 = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome. PMID:21056995

  7. Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.

    PubMed

    Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R; Krah, Nathan M; Dennison, Roberta J; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D; Smith, Lois E H

    2010-12-01

    In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.

  8. Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity.

    PubMed

    McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

    2016-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5-18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA. Copyright © 2016 Elsevier

  9. Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity

    PubMed Central

    McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F.; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

    2016-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the HPA or stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5–18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA. PMID:27286932

  10. Chronic Postnatal Stress Induces Depressive-like Behavior in Male Mice and Programs second-Hit Stress-Induced Gene Expression Patterns of OxtR and AvpR1a in Adulthood.

    PubMed

    Lesse, Alexandra; Rether, Kathy; Gröger, Nicole; Braun, Katharina; Bock, Jörg

    2017-08-01

    Chronic stress (CS) during early life represents a major risk factor for the development of mental disorders, including depression. According to the Two/Multiple-Hit hypothesis, the etiology of neuropsychiatric disorders usually involves multiple stressors experienced subsequently during different phases of life. However, the molecular and cellular mechanisms modulating neuronal and behavioral changes induced by multiple stress experiences are just poorly understood. Since the oxytocinergic and vasopressinergic systems are neuroendocrine modulators involved in environmentally driven adaptations of stress sensitivity we hypothesized that postnatal CS programs oxytocinergic and vasopressinergic receptor expression changes in response to a second stress exposure in young adulthood. First we investigated if postnatal CS (maternal separation + social isolation) induces depressive-like behavior and alters oxytocin receptor (OxtR) and arginine vasopressin receptor type 1a (AvpR1a) gene expression in the hippocampus (HC) of male mice and (2) if a second single stressor (forced swimming, FS) in young adulthood affects gene expression of OxtR and AvpR1a at adulthood dependent on CS pre-experience. We found that postnatal CS induced depressive-like behavior and enhanced AvpR1a expression in HC at young adulthood. Moreover, in line with our hypothesis, only combined stress exposure (CS + FS), but not CS or FS alone, resulted in increased gene expression of OxtR in HC at adulthood. In contrast, AvpR1a expression was decreased in both adult FS and CS + FS animals. Overall, our results provide evidence that CS programs neuroendocrine systems and thereby influences stress responses in later life periods.

  11. Pre-natal and post-natal growth trajectories and childhood cognitive ability and mental health.

    PubMed

    Yang, Seungmi; Tilling, Kate; Martin, Richard; Davies, Neil; Ben-Shlomo, Yoav; Kramer, Michael S

    2011-10-01

    Most studies of the associations between pre-natal or post-natal growth and cognitive ability have been based on children with pathologically slow growth measured between two time points only, rather than children with normal growth trajectories estimated from multiple measures of growth. We investigated the associations of pre-natal and post-natal trajectories in both weight and length/height through the first 5 years of life with cognitive ability and mental health at 6.5 years of age among healthy children. Our study is based on 11 899 children who were born healthy at ≥37 completed weeks with birth weight ≥2500 g and had up to 13 measures of weight and length/height from birth to age 5 years and cognitive ability and behaviour measured at 6.5 years. Using a linear spline random-effects model with 2 knots at 3 and 12 months, we estimated growth trajectories for each child from birth to age 5 years in weight and length/height in four periods: gestational age-specific birth weight and length (pre-natal 'growth'), early infancy (0-3 months), late infancy (3-12 months) and early childhood (1-5 years). We used generalized estimating equations to estimate mean differences in IQ and mental health according to pre-natal and post-natal growth trajectory. IQ was measured using the Wechsler Abbreviated Scales of Intelligence, and mental health was assessed using the Strengths and Difficulties Questionnaire. A 1 standard deviation (SD) in birth weight was positively associated with cognitive ability (0.82 IQ points, 95% CI: 0.54-1.10) after adjusting for confounders. For post-natal weight gain trajectories, a 1 SD faster weight gain was associated with an increase of 0.77 (95% CI: 0.42-1.11) IQ points for early infancy, 0.30 (95% CI: 0.02-0.58) points for late infancy, and 0.40 (95% CI: 0.04-0.76) for early childhood after adjusting for confounders and for earlier growth. For length/height trajectories, the magnitudes of increase in cognitive ability were similar

  12. The effects of pre- and postnatal exposure to the nonsteroidal antiandrogen flutamide on testis descent and morphology in the Albino Swiss rat

    PubMed Central

    KASSIM, NORMADIAH M.; McDONALD, S. W.; REID, O.; BENNETT, N. K.; GILMORE, D. P.; PAYNE, A. P.

    1997-01-01

    Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide during the period from gestational day (d) 10 to birth resulted in feminisation of the external genitalia and the suppression of growth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10% of cases, whereas 50% of testes descended to the scrotum and 40% were located in a suprainguinal ectopic region. Varying degrees of tubule abnormality were seen in the testes of flutamide-treated animals, ranging from completely normal tubules with full spermatogenesis (and the expected frequency of the stages of spermatogenesis) to severely abnormal tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrotally-located testes least; only the latter contained normal tubules. Similarly, intra-abdominal testes were the smallest in weight and contained the least testosterone. By contrast, postnatal treatment of male rats with flutamide from birth to postnatal d 14 did not impair development of the external genitalia, the process of testicular descent or adult spermatogenesis. These findings confirm that androgen blockade during embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but (2) the degree of abnormality of the testes is strongly influenced by location. PMID:9183680

  13. Innovative look at dairy heifer rearing: Effect of prenatal and post-natal environment on later performance.

    PubMed

    Van Eetvelde, M; Opsomer, G

    2017-08-01

    As heifer rearing is a costly investment, dairy farmers have been stimulated to maximize early growth of their calves, mainly by enhanced liquid feeding. However, the long-term effects of this "accelerated growth" are largely unknown. Studies recently performed at Ghent University indicate that in dairy cattle, certain maternal factors (such as young age and high milk yield) and environmental factors (such as high ambient temperatures) create a suboptimal environment for the developing foetus, altering the phenotype of the newborn calf. According to the "thrifty phenotype hypothesis," these metabolic alterations prepare the newborn for similar ("matching") conditions after birth, enhancing its survival during periods of limited feeding. Yet, when an abundance of nutrients is available in post-natal life (e.g., during periods of enhanced feeding), the "mismatch" between pre- and post-natal environment results in an early catch-up growth, with potential negative consequences. The aim of the article was to discuss this mismatch between pre- and post-natal environment in dairy calves. Previous studies, especially in human medicine, have shown catch-up growth to be associated with obesity, fertility problems, metabolic diseases and a reduced lifespan. Hence, we hypothesize that, by applying programs of accelerated growth, our current management system accentuates the mismatch between the pre- and post-natal environment in dairy calves. We can conclude that, although more research is necessary, the current findings point towards a more individual approach when rearing dairy heifers. © 2017 Blackwell Verlag GmbH.

  14. Reduced resistance to oxidative stress during reproduction as a cost of early-life stress.

    PubMed

    Zimmer, Cédric; Spencer, Karen A

    2015-05-01

    Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study.

    PubMed

    Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

    2015-02-01

    To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Mean length-for-age z score was -0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m(2); 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (-41.5 g per twofold increase in ferritin; 95% CI -78 to -5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of -0.06 per 20 nmol/L; 95% CI -0.11 to -0.01) was observed. Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Influence of socio-economic factors on emotional changes during the postnatal period.

    PubMed

    Wszołek, Katarzyna; Żak, Ewa; Żurawska, Joanna; Olszewska, Jolanta; Pięta, Beata; Bojar, Iwona

    2018-03-14

    The aim of the study was to identify socio-economic factors that may influence the emotional changes which occur among new mothers in the first days postpartum. A group of 541 women completed a questionnaire consisting of 30 multiple-choice questions, Edinburgh Postnatal Depression Scale (EPDS), and Hospital Anxiety and Depression Scale (HADS). Statistical calculations were performed with the use of Statistica v.10 and Cytel Studio v. 9.0.0. The findings revealed the presence of factors which might increase the risk of mood disorders during the postpartum period. Women who demonstrate warning symptoms should be screened for postnatal emotional changes and mood swings during their hospitalization after delivery. EPDS seems to be a suitable tool for early detection of emotional disturbances.

  17. ADVERSE PRE- AND POSTNATAL EVENTS REPORTED TO FDA IN ASSOCIATION WITH MATERNAL ATENOLOL TREATMENT IN PREGNANCY

    EPA Science Inventory

    Atenolol is a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy. This study evaluates the reporting frequency of adverse pre- and postnatal outcomes in a series of 70 cases of maternal exposure during gestation, derived from 140 reports to FDA with Ateno...

  18. Tactile stimulation partially prevents neurodevelopmental changes in visual tract caused by early iron deficiency.

    PubMed

    Horiquini-Barbosa, Everton; Gibb, Robbin; Kolb, Bryan; Bray, Douglas; Lachat, Joao-Jose

    2017-02-15

    Iron deficiency has a critical impact on maturational mechanisms of the brain and the damage related to neuroanatomical parameters is not satisfactorily reversed after iron replacement. However, emerging evidence suggest that enriched early experience may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Given the fact that tactile stimulation (TS) treatment has been previously shown to be an effective therapeutic approach and with potential application to humans, here we ask whether exposure to TS treatment, from postnatal day (P) 1 to P32 for 3min/day, could also be employed to prevent neuroanatomical changes in the optic nerve of rats maintained on an iron-deficient diet during brain development. We found that iron deficiency changed astrocyte, oligodendrocyte, damaged fiber, and myelinated fiber density, however, TS reversed the iron-deficiency-induced alteration in oligodendrocyte, damaged fiber and myelinated fiber density, but failed to reverse astrocyte density. Our results suggest that early iron deficiency may act by disrupting the timing of key steps in visual system development thereby modifying the normal progression of optic nerve maturation. However, optic nerve development is sensitive to enriching experiences, and in the current study we show that this sensitivity can be used to prevent damage from postnatal iron deficiency during the critical period. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Pre- and Postnatal Influences on Preschool Mental Health: A Large-Scale Cohort Study

    ERIC Educational Resources Information Center

    Robinson, Monique; Oddy, Wendy H.; Li, Jianghong; Kendall, Garth E.; de Klerk, Nicholas H.; Silburn, Sven R.; Zubrick, Stephen R.; Newnham, John P.; Stanley, Fiona J.; Mattes, Eugen

    2008-01-01

    Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western…

  20. IDENTIFYING CRITICAL WINDOWS OF EXPOSURE FOR CHILDREN'S HEALTH

    EPA Science Inventory

    Several authors have considered the importance of exposure timing and how this affects the outcomes observed, but no one has systematically compiled preconceptional, prentatal, and postnatal developmental exposures and subsequent outcomes. Efforts were undertaken to examine the ...