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  1. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

    PubMed Central

    2011-01-01

    Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring. PMID:22208616

  2. Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring.

    PubMed

    Aerts, L; Van Assche, F A

    2001-01-01

    Gestational diabetes compromises fetal development and induces a diabetogenic effect in the offspring, including the development of gestational diabetes and the transmission of the effect to the next generation. Changes are not limited to glucose and insulin metabolism, and appear to be modulated by alterations at the hypothalamo-hypophyseal axis. In the present work, serum concentrations are given for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both neurotransmitters essential for normal brain development, and for the endogenous neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly below normal values in mildly diabetic mothers, in their fetal and adult offspring, virgin and pregnant, and in the fetuses of these pregnant offspring. GABA and carnosine levels are at the limit of detection in the diabetic mothers and their offspring at every stage. It is concluded that the low taurine, GABA and carnosine levels in diabetic mothers and their fetuses might compromise the normal structural and functional development of the fetal brain. When adult, these offspring present a deficiency of the circulating levels of these neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin secretion. This might contribute to the development of impaired glucose tolerance and gestational diabetes, thereby transmitting the effect to the next generation. PMID:11234622

  3. Vascular dysfunction in the offspring of AT1 receptor antibody-positive pregnant rats during high-salt diet.

    PubMed

    Zhang, Xi; Zhang, Su-Li; Xiong, Hai-Yan; DU, Yun-Hui; Quan, Lin; Yang, Jie; Ma, Xiu-Rui; Liu, Hui-Rong

    2011-04-25

    Antibody against the angiotensin AT1 receptor (AT1-Ab) could disturb placental development. The placenta is the key organ between mother and fetus. Placental damage will seriously impair fetal growth and development in utero, leading to intrauterine growth restriction (IUGR). Based on the fetal origins of adult disease (FOAD) hypothesis, IUGR could increase a propensity to develop adult onset cardiovascular disease (CVD). The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats. Twenty four female rats (8-week-old, AT1-Ab negative) were randomly divided into two groups, immunized and vehicle groups. Immunized group received active immunization to establish AT1-Ab-positive model, while vehicle group was subjected to Freund's adjuvant without antigen. After 8 weeks of immunization, the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay (ELISA). Then all the female rats were mated with normal Wistar male rats and became pregnant. Immunized/vehicle group offspring rats (I offspring/V offspring) were raised to 40-week-old under standard chow feeding. Then the two groups' offspring rats were given a high-salt diet for 12 weeks (4% NaCl in chow feeding). Systolic blood pressure (SBP) was measured dynamically by noninvasive blood pressure system. The vascular ring experiment was performed to detect vascular function and reactivity. As detected by ELISA, the titers of antibody peaked at the 8th week (OD values: 2.75 ± 0.08 vs 0.33 ± 0.01, P < 0.01 vs vehicle group at the same time point). There was no significant difference of SBP between the two groups' offspring rats during the high-salt diet (P > 0.05). Isolated thoracic aortic rings of I offspring had significantly decreased constriction under norepinephrine treatment (P < 0.01 vs V offspring) and significantly decreased dilation under acetylcholine treatment (P < 0.05 vs V offspring). These

  4. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring. PMID:26224008

  5. Prenatal endotoxin exposure alters behavioural pain responses to lipopolysaccharide in adult offspring.

    PubMed

    Hodyl, Nicolette A; Walker, F Rohan; Krivanek, Klara M; Clifton, Vicki L; Hodgson, Deborah M

    2010-05-11

    Evidence suggests that exposure to bacterial endotoxin in early life can alter the production of pro-inflammatory cytokines in later life. This phenomenon may have significant consequences for pain and pain related behaviours as pro-inflammatory cytokines heighten pain sensitivity. This association has yet to be examined. As such, the aim of the present study was to characterize pain behaviours in adult rat offspring following prenatal endotoxin (PE) exposure. Pregnant F344 rats received endotoxin (200microg/kg, s.c.) or saline on gestational days 16, 18 and 20. Pain thresholds were assessed in the adult PE offspring (n=23) and control offspring (n=24) prior to and 4h following administration of lipopolysaccharide (LPS; 100microg/kg, s.c.). Three assays of pain were employed - the hot plate, tail immersion and von Frey tests. Results demonstrated sex-specific effects of prenatal endotoxin on the offspring, with PE males displaying unaltered pain thresholds on the von Frey test post-LPS administration (p<0.01), while male control offspring (n=24) displayed the expected hyperalgesia. Male PE offspring also displayed increased pain thresholds on the tail immersion test (p<0.01), while no change in pain sensitivity was observed in control males following LPS exposure. No difference in response was observed between the female PE and control offspring on the von Frey test, however PE female offspring displayed increased thresholds on the tail immersion test compared to baseline - an effect not observed in the control female offspring. Pain sensitivity on the hot plate test was unaffected by prenatal exposure to endotoxin. These data suggest that prenatal exposure to products associated with bacterial infection have the capacity to alter pain responses, which are evident in the adult offspring. PMID:20184906

  6. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C

    PubMed Central

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

  7. Exposure of pregnant rats to diverse chemicals during pregnancy causes elevated blood pressure in offspring

    EPA Science Inventory

    Objective: Global undernutrition, low protein diet or dexamethasone treatment during pregnancy has been demonstrated in animal models to result in adverse health effects including hypertension and insulln resistance in adult offspring. Most protocols that produce these effects ca...

  8. Maternal ethanol consumption by pregnant guinea pigs causes neurobehavioral deficits and increases ethanol preference in offspring.

    PubMed

    Shea, Kayla M; Hewitt, Amy J; Olmstead, Mary C; Brien, James F; Reynolds, James N

    2012-02-01

    The objective of this study was to test the hypothesis that prenatal exposure to ethanol, through maternal consumption of an aqueous ethanol solution, induces neurobehavioral deficits and increases ethanol preference in offspring. Pregnant Dunkin-Hartley-strain guinea pigs were given 24-h access to an aqueous ethanol solution (5%, v/v) sweetened with sucralose (1 g/l), or water sweetened with sucralose (1 g/l), throughout gestation. Spontaneous locomotor activity was measured in the offspring on postnatal day (PD) 10. The offspring underwent either ethanol preference testing using a two-bottle-choice paradigm beginning on PD 40 or Morris water maze testing using a hidden moving platform design beginning on PD 60. Maternal consumption of a 5% (v/v) ethanol solution (average daily dose of 2.3±0.1 g of ethanol/kg maternal body weight; range: 1.8-2.8 g/kg) decreased offspring birth weight, increased spontaneous locomotor activity, and increased preference for an aqueous ethanol solution. In the Morris water maze test, sucralose-exposed offspring decreased escape latency on the second day of testing, whereas the ethanol-exposed offspring showed no improvement. These data demonstrate that moderate maternal consumption of ethanol produces hyperactivity, enhances ethanol preference, and impairs learning and memory in guinea pig offspring. PMID:22157142

  9. Maternal exercise during pregnancy promotes physical activity in adult offspring.

    PubMed

    Eclarinal, Jesse D; Zhu, Shaoyu; Baker, Maria S; Piyarathna, Danthasinghe B; Coarfa, Cristian; Fiorotto, Marta L; Waterland, Robert A

    2016-07-01

    Previous rodent studies have shown that maternal voluntary exercise during pregnancy leads to metabolic changes in adult offspring. We set out to test whether maternal voluntary exercise during pregnancy also induces persistent changes in voluntary physical activity in the offspring. Adult C57BL/6J female mice were randomly assigned to be caged with an unlocked (U) or locked (L) running wheel before and during pregnancy. Maternal running behavior was monitored during pregnancy, and body weight, body composition, food intake, energy expenditure, total cage activity, and running wheel activity were measured in the offspring at various ages. U offspring were slightly heavier at birth, but no group differences in body weight or composition were observed at later ages (when mice were caged without access to running wheels). Consistent with our hypothesis, U offspring were more physically active as adults. This effect was observed earlier in female offspring (at sexual maturation). Remarkably, at 300 d of age, U females achieved greater fat loss in response to a 3-wk voluntary exercise program. Our findings show for the first time that maternal physical activity during pregnancy affects the offspring's lifelong propensity for physical activity and may have important implications for combating the worldwide epidemic of physical inactivity and obesity.-Eclarinal, J. D., Zhu, S., Baker, M. S., Piyarathna, D. B., Coarfa, C., Fiorotto, M. L., Waterland, R. A. Maternal exercise during pregnancy promotes physical activity in adult offspring. PMID:27033262

  10. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice.

    EPA Science Inventory

    Inorganic arsenic exposure is carcinogenic in humans and rodents. When pregnant mice are exposed to inorganic arsenic in the drinking water their offspring, when adults, develop tumors and proliferative lesions at several sites, such as lung, liver, adrenal, uterus, ovary and ovi...

  11. Intermittent prenatal MDMA exposure alters physiological but not mood related parameters in adult rat offspring.

    PubMed

    Adori, Csaba; Zelena, Dóra; Tímár, Júlia; Gyarmati, Zsuzsa; Domokos, Agnes; Sobor, Melinda; Fürst, Zsuzsanna; Makara, Gábor; Bagdy, György

    2010-01-20

    The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior. PMID:19782105

  12. Safety of classical swine fever virus vaccine strain LOM in pregnant sows and their offspring.

    PubMed

    Lim, Seong-In; Song, Jae-Young; Kim, Jaejo; Hyun, Bang-Hun; Kim, Ha-Young; Cho, In-Soo; Kim, Byounghan; Woo, Gye-Hyeong; Lee, Jung-Bok; An, Dong-Jun

    2016-04-12

    The present study aimed to evaluate the safety of the classical swine fever virus (CSFV) vaccine strain LOM in pregnant sows. Pregnant sows with free CSFV antibody were inoculated with a commercial LOM vaccine during early pregnancy (day 38; n=3) or mid-pregnancy (days 49-59; n=11). In pregnant sows vaccinated during the early stages of gestation, abortion (day 109) was observed in one case, with two stillbirths and seven mummified fetuses. The viability of live-born piglets was 34.9% in sows vaccinated during mid-pregnancy compared with 81.8% in the control group. Post-mortem examination of the organs of the sows and piglets did not reveal any pathological lesions caused by CSFV; however, CSFV RNA was detected in the organs of several vaccinated sows and their litters. The LOM strain was transmitted from sows with free CSFV antibody to their fetus, but did not appear to induce immune tolerance in the offspring from vaccinated pregnant sows. Side effects were not observed in pregnant sows with antibody to the LOM strain: transmission from sow to their litters and stillbirth or mummified fetuses. The LOM strain may induce sterile immunity and provide rapid, long-lasting, and complete protection against CSFV; however, it should be contraindicated in pregnant sows due to potential adverse effects in pregnant sows with free CSFV antibody. PMID:26947495

  13. Prenatal exposure to lipopolysaccharide results in myocardial remodelling in adult murine offspring

    PubMed Central

    2013-01-01

    Background The epigenetic plasticity hypothesis indicates that pregnancy exposure may result in adult-onset diseases, including hypertension, diabetes and cardiovascular disease, in offspring. In a previous study, we discovered that prenatal exposure to inflammatory stimulants, such as lipopolysaccharides (LPS), could lead to hypertension in adult rat offspring. In the present study, we further demonstrate that maternal inflammation induces cardiac hypertrophy and dysfunction via ectopic over-expression of nuclear transcription factor κB (NF- κB), and pyrrolidine dithiocarbamate (PDTC) can protect cardiac function by reducing maternal inflammation. Methods Pregnant SD rats were randomly divided into three groups and intraperitoneally injected with a vehicle, LPS (0.79 mg/kg), or LPS (0.79 mg/kg) plus PDTC (100 mg/kg) at 8 to 12 days of gestation. The offspring were raised until 4 and 8 months old, at which point an echocardiographic study was performed. The left ventricular (LV) mass index and apoptosis were examined. Results At 4 months of age, the LPS offspring exhibited augmented posterior wall thickness. These rats displayed left ventricle (LV) hypertrophy and LV diastolic dysfunction as well as a higher apoptotic index, a higher level of Bax and a lower level of Bcl-2 at 8 months of age. The protein levels of NF-κB (p65) in the myocardium of the offspring were measured at this time. NF-κB protein levels were higher in the myocardium of LPS offspring. The offspring that were prenatally treated with PDTC displayed improved signs of blood pressure (BP) and LV hypertrophy. Conclusions Maternal inflammation can induce cardiac hypertrophy in offspring during aging accompanied with hypertension emergence and can be rescued by the maternal administration of PDTC (the inhibitor of NF-κB). PMID:24764457

  14. Maternal immune activation affects litter success, size and neuroendocrine responses related to behavior in adult offspring.

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2013-07-01

    It is increasingly evident that influences other than genetics can contribute to offspring phenotype. In particular, maternal influences are an important contributing factor to offspring survival, development, physiology and behavior. Common environmental pathogens such as viral or bacterial microorganisms can induce maternal immune responses, which have the potential to alter the prenatal environment via multiple independent pathways. The effects of maternal immune activation on endocrine responses and behavior are less well studied and provide the basis for the current study. Our approach in the current study was two-pronged: 1) quantify sickness responses during pregnancy in adult female hamsters experiencing varying severity of immune responsiveness (i.e., differing doses of lipopolysaccharide [LPS]), and 2) assess the effects of maternal immune activation on offspring development, immunocompetence, hormone profiles, and social behavior during adulthood. Pregnancy success decreased with increasing doses of LPS, and litter size was reduced in LPS dams that managed to successfully reproduce. Unexpectedly, pregnant females treated with LPS showed a hypothermic response in addition to the more typical anorexic and body mass changes associated with sickness. Significant endocrine changes related to behavior were observed in the offspring of LPS-treated dams; these effects were apparent in adulthood. Specifically, offspring from LPS treated dams showed significantly greater cortisol responses to stressful resident-intruder encounters compared with offspring from control dams. Post-behavior cortisol was elevated in male LPS offspring relative to the offspring of control dams, and was positively correlated with the frequency of bites during agonistic interactions, and cortisol levels in both sexes were related to defensive behaviors, suggesting that changes in hypothalamo-pituitary-adrenal axis responsiveness may play a regulatory role in the observed behavioral

  15. Disposition of inorganic mercury in pregnant rats and their offspring

    PubMed Central

    Oliveira, Cláudia S.; Joshee, Lucy; Zalups, Rudolfs K.; Pereira, Maria E.; Bridges, Christy C.

    2015-01-01

    Environmental toxicants such as methylmercury have been shown to negatively impact fetal health. Despite the prevalence of inorganic mercury (Hg2+) in the environment and the ability of methylmercury to biotransform into Hg2+, little is known about the ability of Hg2+ to cross the placenta into fetal tissues. Therefore, it is important to understand the handing and disposition of Hg2+ in the reproductive system. The purpose of the current study was to assess the disposition and transport of Hg2+ in placental and fetal tissues, and to test the hypothesis that acute renal injury in dams can alter the accumulation of Hg2+ in fetal tissues. Pregnant Wistar rats were injected intravenously with 0.5 or 2.5 μmol kg−1 HgCl2 for 6 or 48 h and the disposition of Hg2+ was measured. Accumulation of Hg2+ in the placenta was rapid and dose-dependent. Very little Hg2+ was eliminated during the initial 48 h after exposure. When dams were exposed to the low dose of HgCl2, fetal accumulation of Hg2+ increased between 6 h and 48 h, while at the higher dose, accumulation was similar at each time point. Within fetal organs, the greatest concentration of Hg2+ (nmol/g) was localized in the kidneys, followed by the liver and brain. A dose-dependent increase in the accumulation of Hg2+ in fetal organs was observed, suggesting that continued maternal exposure may lead to increased fetal exposure. Taken together, these data indicate that Hg2+ is capable of crossing the placenta and gaining access to fetal organs in a dose-dependent manner. PMID:26196528

  16. Offspring body size and metabolic profile - effects of lifestyle intervention in obese pregnant women.

    PubMed

    Tanvig, Mette

    2014-07-01

    Worldwide, the prevalence of obesity has reached epidemic proportions. In Denmark one third of all pregnant women are overweight and 12 % are obese. Perhaps even more concerning, a dramatic rise in the prevalence of childhood overweight and obesity has also been evident over recent decades. The obesity epidemic is not simply a consequence of poor diet or sedentary lifestyles. Obesity is a multifactorial condition in which environmental, biological and genetic factors all play essential roles. The Developmental Origins of Health and Disease (DoHaD) hypothesis has highlighted the link between prenatal, perinatal and early postnatal exposure to certain environmental factors and subsequent development of obesity and non-communicable diseases. Maternal obesity and excessive gestational weight gain, resulting in over-nutrition of the fetus, are major contributors to obesity and metabolic disturbances in the offspring. Pregnancy offers the opportunity to modify the intrauterine environment, and maternal lifestyle changes during gestation may confer health benefits to the child. The overall aim with this PhD thesis was to study the effects of maternal obesity on offspring body size and metabolic outcomes, with special emphasis on the effects of lifestyle intervention during pregnancy. The thesis is based on a literature review, description of own studies and three original papers/manuscripts (I, II and III). In paper I, we used data from the Danish Medical Birth Registry. The aim of this paper was to examine the impact of maternal pregestational Body Mass Index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth and to define reference curves for birth AC and weight in offspring of healthy, non-smoking, normal weight women. Data on 366,886 singletons were extracted and analyzed using multivariate linear regressions. We found that birth AC and weight increased with increasing pregestational BMI and decreased with smoking. Reference curves were

  17. Acute stress in pregnant rats: effects on growth rate, learning, and memory capabilities of the offspring.

    PubMed

    Lordi, B; Protais, P; Mellier, D; Caston, J

    1997-11-01

    Growth rate of the offspring of female rats stressed by the presence of a cat at the 10th or the 19th gestational day was lower than that of controls whereas footshocks administered at the same periods did not significantly influence growth rate of the young. Whatever the nature of the stress and the time when it was administered to the mother, the death rate of the young rats was much greater than that in controls. When adult, the offspring of stressed mothers exhibited learning and memory impairments in a delayed alternation task as well as in passive avoidance conditioning. Alteration of these cognitive functions is interpreted in terms of subtle dysfunctions in the development of the nervous system through modifications of the hormonal components of the mothers, particularly eventual alterations of the nervous system biochemistry of the offspring. PMID:9333204

  18. Care of Aging Parents by Adult Offspring.

    ERIC Educational Resources Information Center

    Ames, Barbara D.

    A prevailing myth holds that modern families, characterized by high mobility and individualistic life styles, do not care for their aging members. To assess the quantity and characteristics of the care of noninstitutionalized elderly parents by their adult children, parents and adult child pairs (N=50) responded to interviews. Specific research…

  19. Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring.

    PubMed

    Shin, J H; Shiota, K

    1999-11-01

    Neural tube defects (NTD) are a group of malformations that result from the failure of the neural tube to close early in embryonic development and among the most common congenital malformations in humans. It has been reported that a substantial proportion of NTD in humans can be prevented by folic acid (FA) supplementation prior to conception and during the first months of pregnancy, and myo-inositol (MI) was shown to reduce the incidence of NTD in curly tail mice which are not prevented by FA. Brief maternal hyperthermia (HT) early in pregnancy has been implicated in NTD both in humans and laboratory animals, and anterior NTD including exencephaly and anencephaly are induced frequently when pregnant mice are exposed to HT. We examined the effect of FA or MI supplementation of pregnant mice on the occurrence of heat-induced NTD in the offspring. When pregnant mice were treated with FA (3 mg/kg) daily from gestational day (GD) 0.5 through GD 9.5 and heated at GD 8.5, the prevalence of NTD in the fetuses (26.6%) was significantly lower than the corresponding figure in the HT alone group (38.6%; P < 0.05). However we failed to detect the preventive effect of MI (500 mg/kg). The results of this study suggest that prenatal FA supplementation decreases HT-induced NTD in mice and sufficient FA intake during early pregnancy may be recommended to avoid the birth of malformed children. PMID:10539786

  20. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria

    PubMed Central

    Sharma, Ankur; Conteh, Solomon; Langhorne, Jean; Duffy, Patrick E.

    2016-01-01

    Pregnancy malaria (PM) is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6–7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis. PMID:27467392

  1. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria.

    PubMed

    Sharma, Ankur; Conteh, Solomon; Langhorne, Jean; Duffy, Patrick E

    2016-01-01

    Pregnancy malaria (PM) is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6-7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis. PMID:27467392

  2. A review of the iodine status of UK pregnant women and its implications for the offspring.

    PubMed

    Bath, Sarah C; Rayman, Margaret P

    2015-08-01

    Iodine, as a component of the thyroid hormones, is crucial for brain development and is therefore especially important during pregnancy when the brain is developing most rapidly. While randomised controlled trials of pregnant women in regions of severe iodine deficiency have shown that prenatal iodine deficiency causes impaired cognition, less is known of the effects in regions of mild deficiency. This is relevant to the UK as the World Health Organisation now classifies the UK as mildly iodine deficient, based on a national study of 14-15 year old schoolgirls in 2011. We have previously published a study using samples and data from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC) that found an association between low iodine status in early pregnancy (urinary iodine-to-creatinine ratio <150 μg/g) and lower verbal IQ and reading scores in the offspring. Though the women in ALSPAC were recruited in the early 1990s, the results of the study are still relevant as their iodine status was similar to that reported in recent studies of UK pregnant women. This review discusses the evidence that mild-to-moderate iodine deficiency during pregnancy has deleterious effects on child neurodevelopment and relates that evidence to the data on iodine status in the UK. It has highlighted a need for nationwide data on iodine status of pregnant women and that a randomised controlled trial of iodine supplementation in pregnant women in a region of mild-to-moderate iodine deficiency with child outcomes as the primary endpoint is required. PMID:25663363

  3. Perinatal Nicotine Exposure Increases Angiotensin II Receptor-Mediated Vascular Contractility in Adult Offspring

    PubMed Central

    Xiao, DaLiao; Dasgupta, Chiranjib; Li, Yong; Huang, Xiaohui; Zhang, Lubo

    2014-01-01

    Previous studies have reported that perinatal nicotine exposure causes development of hypertensive phenotype in adult offspring. Aims The present study was to determine whether perinatal nicotine exposure causes an epigenetic programming of vascular Angiotensin II receptors (ATRs) and their-mediated signaling pathway leading to heightened vascular contraction in adult offspring. Main methods Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. The experiments were conducted at 5 months of age of male offspring. Key Findings Nicotine treatment enhanced Angitension II (Ang II)-induced vasoconstriction and 20-kDa myosin light chain phosphorylation (MLC20-P) levels. In addition, the ratio of Ang II-induced tension/MLC-P was also significantly increased in nicotine-treated group compared with the saline group. Nicotine-mediated enhanced constrictions were not directly dependent on the changes of [Ca2+]i concentrations but dependent on Ca2+ sensitivity. Perinatal nicotine treatment significantly enhanced vascular ATR type 1a (AT1aR) but not AT1bR mRNA levels in adult rat offspring, which was associated with selective decreases in DNA methylation at AT1aR promoter. Contrast to the effect on AT1aR, nicotine decreased the mRNA levels of vascular AT2R gene, which was associated with selective increases in DNA methylation at AT2R promoter. Significance Our results indicated that perinatal nicotine exposure caused an epigenetic programming of vascular ATRs and their-mediated signaling pathways, and suggested that differential regulation of AT1R/AT2R gene expression through DNA methylation mechanism may be involved in nicotine-induced heightened vasoconstriction and development of hypertensive phenotype in adulthood. PMID:25265052

  4. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

    PubMed Central

    KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

    2015-01-01

    The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

  5. Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

    PubMed Central

    Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

  6. Resveratrol partially prevents oxidative stress and metabolic dysfunction in pregnant rats fed a low protein diet and their offspring.

    PubMed

    Vega, Claudia C; Reyes-Castro, Luis A; Rodríguez-González, Guadalupe L; Bautista, Claudia J; Vázquez-Martínez, Magaly; Larrea, Fernando; Chamorro-Cevallos, Germán A; Nathanielsz, Peter W; Zambrano, Elena

    2016-03-01

    Protein restriction in pregnancy produces maternal and offspring metabolic dysfunction potentially as a result of oxidative stress. Data are lacking on the effects of inhibition of oxidative stress. We hypothesized that maternal resveratrol administration decreases oxidative stress, preventing, at least partially, maternal low protein-induced maternal and offspring metabolic dysfunction. In the present study, pregnant wistar rats ate control (C) (20% casein) or a protein-restricted (R) (10% casein) isocaloric diet. Half of each group received resveratrol orally, 20 mg kg(-1) day(-1), throughout pregnancy. Post-delivery, mothers and offspring ate C. Oxidative stress biomarkers and anti-oxidant enzymes were measured in placenta, maternal and fetal liver, and maternal serum corticosterone at 19 days of gestation (dG). Maternal (19 dG) and offspring (postnatal day 110) glucose, insulin, triglycerides, cholesterol, fat and leptin were determined. R mothers showed metabolic dysfunction, increased corticosterone and oxidative stress and reduced anti-oxidant enzyme activity vs. C. R placental and fetal liver oxidative stress biomarkers and anti-oxidant enzyme activity increased. R offspring showed higher male and female leptin, insulin and corticosterone, male triglycerides and female fat than C. Resveratrol decreased maternal leptin and improved maternal, fetal and placental oxidative stress markers. R induced offspring insulin and leptin increases were prevented and other R changes were offspring sex-dependent. Resveratrol partially prevents low protein diet-induced maternal, placental and sex-specific offspring oxidative stress and metabolic dysfunction. Oxidative stress is one mechanism programming offspring metabolic outcomes. These studies provide mechanistic evidence to guide human pregnancy interventions when fetal nutrition is impaired by poor maternal nutrition or placental function. PMID:26662841

  7. Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: The importance of in utero vs. lactational exposure

    SciTech Connect

    Castro, David J.; Loehr, Christiane V.; Fischer, Kay A.; Pereira, Clifford B.; Williams, David E.

    2008-12-15

    The fetus and neonate cannot be viewed as 'little adults'; they are highly sensitive to toxicity from environmental chemicals. This phenomenon contributes to the fetal basis of adult disease. One example is transplacental carcinogenesis. Animal models demonstrate that environmental chemicals, to which pregnant women are daily exposed, can increase susceptibility of the offspring to cancer. It is uncertain to what degree in utero vs. lactational exposure contributes to cancer, especially for hydrophobic chemicals such as polyhalogenated biphenyls, ethers, dioxins, furans, etc., which can partition into breast milk. We developed a pregnant mouse model in which exposure to the polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), during late gestation, produces an aggressive T-cell lymphoma in offspring between 3 and 6 months of age. Survivors exhibit multiple lung and liver (males) tumors. Here, we adopt a cross-foster design with litters born to dams treated with DBP exchanged with those born to dams treated with vehicle. Exposure to DBP in utero (about 2 days) produced significantly greater mortality than residual DBP exposure only through breast milk (3 weeks of lactation). As previously observed pups in all groups with an ahr{sup b-1/d} ('responsive') genotype were more susceptible to lymphoma mortality than ahr{sup d/d} ('non-responsive') siblings. At termination of the study at 10 months, mice exposed in utero also had greater lung tumor multiplicity than mice exposed only during lactation. Our results demonstrate that short exposure to DBP during late gestation presents a greater risk to offspring than exposure to this very hydrophobic PAH following 3 weeks of nursing.

  8. Levels of maternal care in dogs affect adult offspring temperament.

    PubMed

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  9. Levels of maternal care in dogs affect adult offspring temperament

    PubMed Central

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  10. Classical swine fever virus strain "C" protects the offspring by oral immunisation of pregnant sows.

    PubMed

    Kaden, V; Lange, E; Steyer, H; Lange, B; Klopfleisch, R; Teifke, J P; Bruer, W

    2008-07-27

    The aim of this study was to evaluate if oral immunisation of wild sows protects the fetuses from transplacental infection. Two experiments were carried out with gilts vaccinated orally with C-strain virus approximately 5 weeks after insemination. They were challenged at mid-gestation with highly virulent classical swine fever virus (CSFV) or moderately virulent field virus. The results revealed that oral vaccination has no negative impact on the pregnancy, and all vaccinated sows developed neutralising antibodies. After infection no symptoms were detected in the six vaccinated-infected sows. Challenge virus could neither be found in blood, nasal and fecal swabs or saliva nor in organs sampled at necropsy. Likewise, all fetuses originating from vaccinated sows were virologically and serologically negative. In contrast, the controls developed a short viremia and as a result of the transplacental infection all fetuses were CSFV positive. In addition, 22 serologically positive wild sows of an endemically infected area, where oral vaccination had also been carried out, and their offspring were free from CSFV or viral RNA. Our results confirm that oral immunisation of pregnant wild sows with C-strain vaccine may protect the fetuses against CSF. PMID:18321665

  11. Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

    PubMed

    Dobson, Christine C; Thevasundaram, Kersh; Mongillo, Daniel L; Winterborn, Andrew; Holloway, Alison C; Brien, James F; Reynolds, James N

    2014-11-01

    Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE). The objective of this study was to test the hypothesis that CPEE alters expression of insulin and IGF signaling molecules in the prefrontal cortex and liver of adult guinea pig offspring. Pregnant Dunkin-Hartley-strain guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (nutritional control) throughout gestation. Fasting blood glucose concentration was measured in male and female offspring at postnatal day 150-200, followed by euthanasia, collection of prefrontal cortex and liver, and RNA extraction. IGF-1, IGF-1 receptor (IGF-1R), IGF-2, IGF-2 receptor (IGF-2R), insulin receptor substrate (IRS)-1, IRS-2, and insulin receptor (INSR) mRNA expression levels were measured in tissues using quantitative real-time PCR. The mean maternal blood ethanol concentration was 281 ± 15 mg/dL at 1 h after the second divided dose of ethanol on GD 57. CPEE resulted in increased liver weight in adult offspring, but produced no difference in fasting blood glucose concentration compared with nutritional control. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1R, and IGF-2, and increased IRS-2 mRNA expression in male offspring only compared with nutritional control. Female CPEE offspring had decreased INSR hepatic mRNA expression compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in CPEE offspring compared with nutritional control. The data demonstrate that CPEE alters both central and peripheral expression of insulin and IGF signaling

  12. Persistent Interneuronopathy in the Prefrontal Cortex of Young Adult Offspring Exposed to Ethanol In Utero

    PubMed Central

    Skorput, Alexander G. J.; Gupta, Vivek P.; Yeh, Pamela W. L.

    2015-01-01

    Gestational exposure to ethanol has been reported to alter the disposition of tangentially migrating GABAergic cortical interneurons, but much remains to be elucidated. Here we first established the migration of interneurons as a proximal target of ethanol by limiting ethanol exposure in utero to the gestational window when tangential migration is at its height. We then asked whether the aberrant tangential migration of GABAergic interneurons persisted as an enduring interneuronopathy in the medial prefrontal cortex (mPFC) later in the life of offspring prenatally exposed to ethanol. Time pregnant mice with Nkx2.1Cre/Ai14 embryos harboring tdTomato-fluorescent medial ganglionic eminence (MGE)-derived cortical GABAergic interneurons were subjected to a 3 day binge-type 5% w/w ethanol consumption regimen from embryonic day (E) 13.5–16.5, spanning the peak of corticopetal interneuron migration in the fetal brain. Our binge-type regimen increased the density of MGE-derived interneurons in the E16.5 mPFC. In young adult offspring exposed to ethanol in utero, this effect persisted as an increase in the number of mPFC layer V parvalbumin-immunopositive interneurons. Commensurately, patch-clamp recording in mPFC layer V pyramidal neurons uncovered enhanced GABA-mediated spontaneous and evoked synaptic transmission, shifting the inhibitory/excitatory balance toward favoring inhibition. Furthermore, young adult offspring exposed to the 3 day binge-type ethanol regimen exhibited impaired reversal learning in a modified Barnes maze, indicative of decreased PFC-dependent behavioral flexibility, and heightened locomotor activity in an open field arena. Our findings underscore that aberrant neuronal migration, inhibitory/excitatory imbalance, and thus interneuronopathy contribute to indelible abnormal cortical circuit form and function in fetal alcohol spectrum disorders. SIGNIFICANCE STATEMENT The significance of this study is twofold. First, we demonstrate that a time

  13. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    PubMed

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation. PMID:27262980

  14. The different effects of LPS and poly I:C prenatal immune challenges on the behavior, development and inflammatory responses in pregnant mice and their offspring.

    PubMed

    Arsenault, Dany; St-Amour, Isabelle; Cisbani, Giulia; Rousseau, Louis-Simon; Cicchetti, Francesca

    2014-05-01

    In recent years, in vivo animal models of prenatal infection have been developed in an attempt to recreate behavioral and neuropathological features associated to a number of neurological and neuropsychiatric disorders. However, these models are still in their emerging phase and a better understanding of how these types of infections relate to adult-onset of brain-related disorders is needed. Here, we undertook an extensive behavioral characterization of both pregnant females and their pups following late gestational exposure (from gestational days (GD) 15-17) to either lipopolysaccharide (LPS; 120μg/kg i.p.) or polyinosinic:polycytidylic acid (poly I:C; 5mg/kg i.v.). We observed that both LPS and poly I:C treatments produced anxiety-like behaviors in treated pregnant females, although to a lesser extent with LPS. LPS injections, but not poly I:C, led to reduced food intake and consequently decreased weight gain in pregnant dams. In pups, poly I:C treatments triggered a delay in growth and sensorimotor development, as evaluated by righting, geotaxis and grasping reflexes. At the cellular level, both toxins induced an initial inflammatory response while only LPS reduced the expression of brain cell markers in foetuses (GFAP and NeuN), which was no longer observable at postnatal day (PnD) 10. Higher levels of IL-2, IL-5 and IL-6 in plasma and an upregulation of the metabotropic receptor 5 (mGluR5) in foetal brains of 10-day-old offspring prenatally exposed to poly I:C was also observed. Interestingly, the increased mGluR5 expression correlated with impairments of the righting reflex. This study is the first to directly compare reflex development following LPS and poly I:C prenatal immune challenges in mice and sheds light onto the different patterns of behavior and pathology in dams and their offspring. PMID:24384468

  15. Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring.

    PubMed

    Ibrahim, Beatriz Silva; Barioni, Éric Diego; Heluany, Cíntia; Braga, Tárcio Teodoro; Drewes, Carine Cristiane; Costa, Silvia Goes; Câmara, Niels Olsen Saraiva; Farsky, Sandra Helena Poliselli; Lino-Dos-Santos-Franco, Adriana

    2016-06-01

    Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150mg/kg, gavage) or vehicle (distilled water, gavage) 1h before FA exposure (0.92mg/m(3), 1h/day, 5days/week), for 21days, and the 30days old offspring were submitted to LPS injection (Salmonella abortus equi, 5mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense. PMID:27020608

  16. Perinatal undernutrition programmes thyroid function in the adult rat offspring.

    PubMed

    Ayala-Moreno, Rosario; Racotta, Radu; Anguiano, Brenda; Aceves, Carmen; Quevedo, Lucía

    2013-12-01

    Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40% food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3'-triiodothyronine (T3) levels but had normal thyroxine (T4) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T3 (total and free) and total T4 levels, but low free T4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100%) and T4 (non-response v. 17%) levels, a significant decrease in leptin levels (75 v. 32%) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus-pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism. PMID:23800456

  17. Autobiographical memory in adult offspring of traumatized parents with and without posttraumatic stress symptoms.

    PubMed

    Wittekind, Charlotte E; Jelinek, Lena; Moritz, Steffen; Muhtz, Christoph; Berna, Fabrice

    2016-08-30

    The present study examined potential transgenerational effects of trauma on autobiographical memory in adult offspring of elderly participants with and without PTSD symptoms who were exposed to an early trauma during childhood. As traumatization is associated with reduced memory specificity for past events, we hypothesized that offspring of traumatized parents might be exposed to a less elaborative narrative style, which, in turn, might result in less specific autobiographical memories in the offspring. Results show that autobiographical memory specificity did not differ significantly between adult offspring of traumatized elderly participants with PTSD symptoms, without PTSD symptoms, and non-traumatized elderly participants. PMID:27322841

  18. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia.

    PubMed

    Reyes, Laura M; Kirschenman, Raven; Quon, Anita; Morton, Jude S; Shah, Amin; Davidge, Sandra T

    2015-09-01

    Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P < 0.05). In male offspring, exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P ≤ 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID:26157059

  19. Pregnant Mothers with Resolved Anxiety Disorders and Their Offspring Have Reduced Heart Rate Variability: Implications for the Health of Children

    PubMed Central

    Braeken, Marijke A. K. A.; Kemp, Andrew H.; Outhred, Tim; Otte, Renée A.; Monsieur, Geert J. Y. J.; Jones, Alexander; Van den Bergh, Bea R. H.

    2013-01-01

    Objective Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments. Methods The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children’s fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version. Results HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months. Conclusions Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology. PMID:24340091

  20. Administration of Non-Absorbable Antibiotics to Pregnant Mice to Perturb the Maternal Gut Microbiota Is Associated with Alterations in Offspring Behavior

    PubMed Central

    Tochitani, Shiro; Matsuzaki, Hideo

    2016-01-01

    There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7±3.4%) than in control offspring (42.1±6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2±5.0%) than in control offspring (16.4±3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7–8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring. PMID:26789865

  1. Parental Depression as a Moderator of Secondary Deficits of Depression in Adult Offspring

    ERIC Educational Resources Information Center

    Timko, Christine; Cronkite, Ruth C.; Swindle, Ralph; Robinson, Rebecca L.; Sutkowi, Anne; Moos, Rudolf H.

    2009-01-01

    This study examined whether having a depressed parent intensifies the secondary deficits that often co-occur with offspring's depression symptoms. The sample was adult offspring of parents who had been diagnosed with depression 23 years earlier (N = 143) and demographically matched nondepressed parents (N = 197). Respondents completed mailed…

  2. Zinc-α2-Glycoprotein Is Unrelated to Gestational Diabetes: Anthropometric and Metabolic Determinants in Pregnant Women and Their Offspring

    PubMed Central

    Näf, Silvia; Escote, Xavier; Yañez, Rosa Elena; Ballesteros, Mónica; Simón, Inmaculada; Gil, Pilar

    2012-01-01

    Context Zinc-α2-Glycoprotein (ZAG) is an adipokine with lipolytic action and is positively associated with adiponectin in adipose tissue. We hypothesize that ZAG may be related with hydrocarbonate metabolism disturbances observed in gestational diabetes mellitus (GDM). Objective The aim of this study was to analyze serum ZAG concentration and its relationship with carbohydrate metabolism in pregnant women and its influence on fetal growth. Design 207 pregnant women (130 with normal glucose tolerance (NGT) and 77 with GDM) recruited in the early third trimester and their offspring were studied. Cord blood was obtained at delivery and neonatal anthropometry was assessed in the first 48 hours. ZAG was determined in maternal serum and cord blood. Results ZAG concentration was lower in cord blood than in maternal serum, but similar concentration was observed in NGT and GDM pregnant women. Also similar levels were found between offspring of NGT and GDM women. In the bivariate analysis, maternal ZAG (mZAG) was positively correlated with adiponectin and HDL cholesterol, and negatively correlated with insulin and triglyceride concentrations, and HOMA index. On the other hand, cord blood ZAG (cbZAG) was positively correlated with fat-free mass, birth weight and gestational age at delivery. After adjusting for confounding variables, gestational age at delivery and HDL cholesterol emerged as the sole determinants of cord blood ZAG and maternal ZAG concentrations, respectively. Conclusion mZAG was not associated with glucose metabolism during pregnancy. ZAG concentration was lower in cord blood compared with maternal serum. cbZAG was independently correlated with gestational age at delivery, suggesting a role during the accelerated fetal growth during latter pregnancy. PMID:23272038

  3. The scent of stress: environmental challenge in the peripartum environment of mice affects emotional behaviours of the adult offspring in a sex-specific manner.

    PubMed

    Lerch, S; Dormann, C; Brandwein, C; Gass, P; Chourbaji, S

    2016-06-01

    Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data. PMID:26408077

  4. Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of low-protein pregnancies.

    PubMed

    Catta-Preta, Mariana; Oliveira, Daniel Alves; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2006-12-23

    We investigated the effect of fish oil (FO) treatment on cardiorenal structure of adult offspring from low-protein pregnancies. Three month old offspring were assigned to eight groups (four male groups and four female groups, n=8 each) (NP=normal-protein diet, LP=low-protein diet): NP, LP, NP plus FO, and LP plus FO. Left ventricle and kidney were analyzed with light microscopy and stereology. The both sexes of LP offspring showed 30% lower birth weights than the respective NP offspring and high blood pressure (BP) levels in adulthood which was efficiently reduced by FO treatment. In the heart, FO treated the cardiomyocyte hypertrophy, the vascularization impairment, and decreased the cardiomyocyte loss usually observed in adult LP offspring. In the kidney, FO treated, in the male, the imbalance of the cortex-to-medulla ratio observed in both sexes of LP offspring, and reduced the glomeruli loss in the LP offspring. The positive correlation between the number of cardiomyocyte nuclei later in life and the body mass (BM) at birth was significant only in both sexes of LP offspring and this correlation disappeared in LP plus fish oil offspring. The positive correlation between the number of glomeruli later in life and the BM at birth was significant in NP male offspring and in both sexes of LP offspring. In conclusion, FO supplement, which is a rich source of n-3 fatty acids (DHA and EPA), has beneficial effects on BP control and cardiac and renal adverse remodeling usually seen in offspring of the LP pregnancies. PMID:17020772

  5. The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats.

    PubMed

    Karbalaei, Narges; Ghasemi, Asghar; Hedayati, Mehdi; Godini, Aliashraf; Zahediasl, Saleh

    2014-04-01

    Previous studies have recently shown that maternal hypothyroidism leads to impaired glucose metabolism and reduced insulin secretion in adult offspring in rats. The aim of this study was to locate the defect in the insulin secretion pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid (FH) group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An intravenous glucose tolerance test was carried out on 5-month-old male offspring. In in vitro studies, the effects of various secretagogues and inhibitors acting at different levels of the insulin secretion cascade were investigated, and insulin content, insulin secretion and glucokinase activity of the islets were compared. Although insulin content of the FH islets did not differ from that of control islets, insulin secretion from FH islets was reduced when it was challenged by glucose or arginine. Compared with control islets, activities of both hexokinase and glucokinase were also significantly decreased in the FH islets. Although, in both groups, increasing glibenclamide and nifedipine concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased insulin secretion, respectively, the percentage of changes in secretion of FH islets was significantly lower compared with control islets. The response of FH islets to high extracellular potassium concentration and diazoxide was also significantly lower than that of the control islets. These findings demonstrate that impaired insulin secretion in the FH group is probably related to alterations in different steps of the insulin secretion pathway and not in the insulin pool of β-cells. PMID:24097159

  6. Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors.

    PubMed

    Seppänen, Viivi I; Artama, Miia S; Malila, Nea K; Pitkäniemi, Janne M; Rantanen, Matti E; Ritvanen, Annukka K; Madanat-Harjuoja, Laura-Maria

    2016-10-15

    Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades. PMID:27280956

  7. OXIDATIVE STRESS CONTRIBUTES TO SEX DIFFERENCES IN BLOOD PRESSURE IN ADULT GROWTH RESTRICTED OFFSPRING

    PubMed Central

    Ojeda, Norma B.; Hennington, Bettye Sue; Williamson, Danielle T.; Hill, Melanie L.; Betson, Nicole E.E.; Sartori-Valinotti, Julio C.; Reckelhoff, Jane F.; Royals, Thomas P.; Alexander, Barbara T.

    2013-01-01

    Numerous experimental studies suggest that oxidative stress contributes to the pathophysiology of hypertension and importantly, that oxidative stress plays a more definitive role in mediating hypertension in males than in females. Intrauterine growth-restriction induced by reduced uterine perfusion initiated at day 14 of gestation in the rat programs hypertension in adult male growth-restricted offspring; yet, female growth-restricted offspring are normotensive. The mechanisms mediating sex differences in blood pressure in adult growth-restricted offspring are not clear. Thus, this study tested the hypothesis that sex specific differences in renal oxidative stress contribute to the regulation of blood pressure in adult growth-restricted offspring. A significant increase in blood pressure measured by telemetry in male growth-restricted offspring (P<0.05) was associated with a marked increase in renal markers of oxidative stress (P<0.05). Chronic treatment with the antioxidant tempol had no effect on blood pressure in male control offspring, but it normalized blood pressure (P<0.05) and renal markers of oxidative stress (P<0.05) in male growth-restricted relative to male control. Renal markers of oxidative stress were not elevated in female growth-restricted offspring; however, renal activity of the antioxidant catalase was significantly elevated relative to female control (P<0.05). Chronic treatment with tempol did not significantly alter oxidative stress or blood pressure measured by telemetry in female offspring. Thus, these data suggest that sex differences in renal oxidative stress and antioxidant activity are present in adult growth-restricted offspring, and that oxidative stress may play a more important role in modulating blood pressure in male, but not female growth-restricted offspring. PMID:22585945

  8. Enhanced Mesenteric Arterial Responsiveness to Angiotensin II Is Androgen Receptor-Dependent in Prenatally Protein-Restricted Adult Female Rat Offspring1

    PubMed Central

    Sathishkumar, Kunju; Balakrishnan, Meena P.; Yallampalli, Chandrasekhar

    2014-01-01

    ABSTRACT Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally protein-restricted rats exhibit an enhanced responsiveness to angiotensin

  9. Zinc Supplementation to Pregnant Rats with Adequate Zinc Nutriture Suppresses Immune Functions in their Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Pronounced zinc (Zn) deficiency during pregnancy is associated with thymic and splenic atrophy and immunosuppression. However, our knowledge about consequences of marginal Zn deficiency and Zn supplementation during pregnancy on immune function in the offspring is limited. Aim: To study ...

  10. Mothers' exercise during pregnancy programs vasomotor function in adult offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The intrauterine environment is influenced by maternal behavior and known to influence lifelong atherosclerotic disease susceptibility in offspring. The purpose of this investigation was to test the hypothesis that maternal exercise during pregnancy increases endothelial function in offs...

  11. The Effects of Parental Health Shocks on Adult Offspring Smoking Behavior and Self-Assessed Health.

    PubMed

    Darden, Michael; Gilleskie, Donna

    2016-08-01

    An important avenue for smoking deterrence may be through familial ties if adult smokers respond to parental health shocks. In this paper, we merge the Original Cohort and the Offspring Cohort of the Framingham Heart Study to study how adult offspring smoking behavior and subjective health assessments vary with elder parent smoking behavior and health outcomes. These data allow us to model the smoking behavior of adult offspring over a 30-year period contemporaneously with parental behaviors and outcomes. We find strong 'like father, like son' and 'like mother, like daughter' correlations in smoking behavior. We find that adult offspring significantly curtail their own smoking following an own health shock; however, we find limited evidence that offspring smoking behavior is sensitive to parent health, with the notable exception that women significantly reduce both their smoking participation and intensity following a smoking-related cardiovascular event of a parent. We also model the subjective health assessment of adult offspring as a function of parent health, and we find that women report significantly worse health following the smoking-related death of a parent. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25981179

  12. Maternal Undernutrition Induces Premature Reproductive Senescence in Adult Female Rat Offspring

    PubMed Central

    Khorram, Omid; Keen-Rinehart, Erin; Chuang, Tsai-Der; Ross, Michael G.; Desai, Mina

    2014-01-01

    Objective To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring. Design Animal (rat) study. Setting Research Laboratory. Animals Female Sprague-Dawley rats. Intervention(s) Food restriction during the second half of pregnancy in rats. Main Outcome Measures Circulating gonadotropins, Anti-Mullerian Hormone (AMH), ovarian morphology, estrous cyclicity and gene expression studies in the hypothalamus and ovary in 1 day old (P1) and aging adult offspring. Results Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating testosterone (T), increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma Leuteinizing (LH/)/Follicle Stimulating hormone (FSH) levels, reduced estradiol (E2) levels and no changes in AMH in adult LBW offspring compared to control offspring. Hypothalamic expression of leptin receptor (OBRb), estrogen receptor-α (ER-α) and Gonadotropin Releasing hormone (GnRH) protein were altered in an age-dependent manner with increased ObRb, ER-α expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami. Conclusion Our data indicates that the maternal nutritional environment programs reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to development of obesity and hyperleptinemia in these animals in adult life. PMID:25439841

  13. Effect of Valeriana fauriei extract on the offspring of adult rats exposed to prenatal stress.

    PubMed

    Lee, Hwayoung; Won, Hansol; Im, Jiyun; Kim, Young Ock; Lee, Sanghyun; Cho, Ik-Hyun; Kim, Hyung-Ki; Kwon, Jun-Tack; Kim, Hak-Jae

    2016-07-01

    Exposing a pregnant female to stress is a risk factor for the development of psychiatric disorders in the offspring. In the present study, we examined the effects of an extract of Valeriana fauriei (VF) root (100 mg/kg/day, administered on postnatal days 35-56) on behavioral patterns as well as protein expression in the prefrontal cortex of the offspring of prenatally-stressed rats. Modified behavioral tests, including the forced swim test, the open field test, a social interaction test and the prepulse inhibition test were performed and many of the parameters were found to decrease in the offspring of the rats exposed to PNS compared with the offspring of the non-stressed rats. Western blot and immunohistochemical analyses of the prefrontal cortex revealed that the downregulation of several neurodevelopmental proteins in the offspring of rats dams exposed to PNS was reversed after treatment with VF extract. These findings demonstrate that the downregulation of several proteins in the prefrontal cortex of the offspring of prenatally‑stressed rats may be associated with subsequent behavioral changes, and that these phenomena recovered following VF treatment. Our results suggest that VF decreases the incidence of prenatal stress related-psychiatric disorders, such as depression and schizophrenia. PMID:27220809

  14. Effects of quercetin on predator stress-related hematological and behavioral alterations in pregnant rats and their offspring.

    PubMed

    Toumi, Mohamed L; Merzoug, Sameha; Tahraoui, Abdelkrim

    2016-06-01

    This study aims at investigating the effect of a psychogenic stress during gestation on the behaviour and haematological indices in dams as well as on the neonatal haematological status and periadolescent behaviour in their offspring. Moreover, the ability of quercetin, a natural flavonoid, to prevent the stress-induced changes was estimated. Pregnant Wistar rats were pretreated with quercetin before the exposure to a predator stress on gestational day 19. Post-stress maternal anxiety-like behaviour was assessed with a concomitant haematological analysis. In the offspring, haematological analysis and behavioural testing were performed during the postnatal stage. Our results revealed that predator stress causes an anxiety-like behaviour in dams along with a decrease in erythrocytes, a microcytosis, and a thrombocytosis. Prenatally stressed neonates manifested microcytosis and thrombocytosis with a significant polycythemia. Signs of motor hyperactivity, anxiety-like behaviour, and memory dysfunction were detected at periadolescence. Quercetin pretreatment alleviated the stress-induced behavioural and haematological impairments in dams but failed to attenuate the haematological changes in neonates. A sex-dependent effect of quercetin on behaviour was found at periadolescence. Our findings suggest that, besides a beneficial effect on haematological and behavioural anomalies in traumatized dams, quercetin may lastingly modulate the behaviour of their progeny. PMID:27240984

  15. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal. PMID:23831729

  16. Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats.

    PubMed

    Hsieh, Chih-Sung; Li, Shih-Wen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Su, Chung-Hao; Huang, Li-Tung

    2016-08-01

    Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain. PMID:27272689

  17. Parental Divorce and Interpersonal Trust in Adult Offspring.

    ERIC Educational Resources Information Center

    King, Valarie

    2002-01-01

    Examines whether parental divorce is associated with offspring trust in parents, intimate partners, and others. Results reveal that although parental divorce is negatively associated with trust, these effects largely disappear once the quality of the past parent-teen relationship is taken into account. (Contains 48 references and 4 tables.) (GCP)

  18. High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

    PubMed Central

    Rivera, M T; Marques de Araujo, S; Lucas, R; Deman, J; Truyens, C; Defresne, M P; de Baetselier, P; Carlier, Y

    1995-01-01

    Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals. Fetuses from infected mice exhibited significantly more cells containing TNF-alpha mRNA in their thymus than fetuses from uninfected mothers. When infected 2 months after birth, offspring born to infected and uninfected mothers displayed similar amounts of circulating TNF-alpha during chronic infection, whereas this cytokine was only weakly detectable during the acute phase of the disease. An intravenous injection of lipopolysaccharide during acute infection strongly increased the production of TNF-alpha in offspring born to infected mothers to levels higher than those in progeny from uninfected mice. These results suggest that TNF-alpha is an important cytokine in the feto-maternal relationship during T. cruzi infection and that fetuses and offspring of infected mothers are primed to produce elevated levels of TNF-alpha. PMID:7822027

  19. Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring.

    PubMed

    Baier, Carlos J; Pallarés, María E; Adrover, Ezequiela; Monteleone, Melisa C; Brocco, Marcela A; Barrantes, Francisco J; Antonelli, Marta C

    2015-01-01

    Prenatal stress (PS) strongly impacts fetal brain development and function in adulthood. In normal aging and Alzheimer's disease, there is hypothalamic-pituitary-adrenal axis dysfunction and loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors (nAChRs). This study investigated whether prenatal restraint stress affects nAChR expression in the brain of adult offspring. For PS, pregnant dams were placed in a plastic restrainer for 45 min, three times daily during the last week of pregnancy; controls were undisturbed. Male offspring were analyzed at postnatal day (PND) 60 (n = 4 rats per group). Western blot (WB) and fluorescence microscopy showed that PS decreased α7-AChR subunit expression (∼50%) in the frontal cortex in the adult offspring. PS decreased significantly the number of α7-AChR-expressing cells in the medial prefrontal cortex (by ∼25%) and in the sensory-motor cortex (by ∼20%) without affecting the total cell number in those areas. No alterations were found in the hippocampus by quantitative polymerase chain reaction (qPCR), or WB analysis, but a detailed fluorescence microscopy analysis showed that PS affected α7-AChR mainly in the CA3 and dentate gyrus subfields: PS decreased α7-AChR subunit expression by ∼25 and ∼30%, respectively. Importantly, PS decreased the number of α7-AChR-expressing cells and the total cell number (by ∼15 and 20%, respectively) in the dentate gyrus. PS differently affected α4-AChR: PS impaired its mRNA expression in the frontal cortex (by ∼50%), without affecting protein levels. These results demonstrate that disturbances during gestation produce long-term alterations in the expression pattern of α7-AChR in rat brain. PMID:25798813

  20. Neuropsychological functioning in posttraumatic stress disorder following forced displacement in older adults and their offspring.

    PubMed

    Jelinek, Lena; Wittekind, Charlotte E; Moritz, Steffen; Kellner, Michael; Muhtz, Christoph

    2013-12-15

    The aim of the present study was to investigate neuropsychological performance in an untried trauma sample of older adults displaced during childhood at the end of World War II (WWII) with and without posttraumatic stress disorder (PTSD) as well as transgenerational effects of trauma and PTSD on their offspring. Displaced older adults with (n=20) and without PTSD (n=24) and nondisplaced healthy individuals (n=11) as well as one of their respective offspring were assessed with a large battery of cognitive tests (primarily targeting memory functioning). No evidence for deficits in neuropsychological performance was found in the aging group of displaced people with PTSD. Moreover, no group difference emerged in the offspring groups. Findings may be interpreted as first evidence for a rather resilient PTSD group of older adults that is available for assessment 60 years after displacement. PMID:23896354

  1. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  2. Altered engagement of autobiographical memory networks in adult offspring of postnatally depressed mothers.

    PubMed

    Macdonald, Birthe; Murray, Lynne; Moutsiana, Christina; Fearon, Pasco; Cooper, Peter J; Halligan, Sarah L; Johnstone, Tom

    2016-07-01

    Maternal depression is associated with increased risk for offspring mood and anxiety disorders. One possible impact of maternal depression during offspring development is on the emotional autobiographical memory system. We investigated the neural mechanisms of emotional autobiographical memory in adult offspring of mothers with postnatal depression (N=16) compared to controls (N=21). During fMRI, recordings of participants describing one pleasant and one unpleasant situation with their mother and with a companion, were used as prompts to re-live the situations. Compared to controls we predicted the PND offspring would show: greater activation in medial and posterior brain regions implicated in autobiographical memory and rumination; and decreased activation in lateral prefrontal cortex and decreased connectivity between lateral prefrontal and posterior regions, reflecting reduced control of autobiographical recall. For negative situations, we found no group differences. For positive situations with their mothers, PND offspring showed higher activation than controls in left lateral prefrontal cortex, right frontal pole, cingulate cortex and precuneus, and lower connectivity of right middle frontal gyrus, left middle temporal gyrus, thalamus and lingual gyrus with the posterior cingulate. Our results are consistent with adult offspring of PND mothers having less efficient prefrontal regulation of personally relevant pleasant autobiographical memories. PMID:27208693

  3. Mediators of Aggression Among Young Adult Offspring of Depressed Mothers

    PubMed Central

    Keenan-Miller, Danielle; Hammen, Constance; Brennan, Patricia A.

    2010-01-01

    The current paper explores the connection between maternal depression and offspring aggression during the transition to adulthood, expanding the scope of prior research on this topic. Both family-level factors (including parent-child relationship quality and maternal relationship quality) and youth factors (including depression history and social functioning in mid-adolescence) were tested as potential mediators in a longitudinal community sample of 710 youth at ages 15 and 20. The results suggest that maternal depression confers a risk for higher levels of aggressive behavior by offspring at age 20. Structural Equation Models suggested that the association between maternal depression and youth aggression is fully mediated by youth history of depression by mid-adolescence, even when accounting for the stability of aggression between ages 15 and 20. Parent-child relationship quality, youth social functioning, and maternal relationship quality were not unique mediators of this association. Limitations and implications are discussed. PMID:20919790

  4. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    PubMed

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR. PMID:26499267

  5. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    SciTech Connect

    Martinez–Arguelles, D.B.; McIntosh, M.; Rohlicek, C.V.; Culty, M.; Zirkin, B.R.; Papadopoulos, V.

    2013-01-01

    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 pressure 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.

  6. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    PubMed Central

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    “Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  7. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women.

    PubMed

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    "Metabolic Equivalent" (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O₂/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35-41, n = 46), women 24-53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  8. Maternal Immune Activation Alters Nonspatial Information Processing in the Hippocampus of the Adult Offspring

    PubMed Central

    Ito, Hiroshi T.; Smith, Stephen E. P.; Hsiao, Elaine; Patterson, Paul H.

    2010-01-01

    The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors. PMID:20227486

  9. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg;P=0.007), and nitric oxide synthase inhibition (withl-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment withl-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%;P<0.05), and this difference could be normalized byl-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. PMID:26928803

  10. Implications of maternal conditions and pregnancy course on offspring's medical problems in adult life.

    PubMed

    von Ehr, Julia; von Versen-Höynck, Frauke

    2016-10-01

    In the last decade, numerous epidemiological, clinical and experimental data show that periconceptional, perinatal and postnatal environment determines the offspring's risk for later-life chronic disease. For this phenomenon, the term "fetal" or "perinatal programming" is used. In exposed offspring already in childhood and early adulthood, metabolic and cardiovascular changes can be observed, leading to obesity, diabetes and hypertension. Nowadays, the mode of conception (e.g., in vitro fertilization), maternal metabolic conditions (e.g., undernutrition, overnutrition, diabetes) and complications during pregnancy (e.g., preeclampsia, intrauterine growth restriction) are suspected to be negative predictors for offspring's long-term health. Mechanisms responsible for these effects still remain mainly unclear, but include epigenetic, transcriptional, endoplasmic reticulum stress, and reactive oxygen species. This review presents a piece of the puzzle with regards to periconceptional and early perinatal conditions determining later-life risk for chronic adult disease. PMID:27522600

  11. Management of the pregnant mare and long-term consequences on the offspring.

    PubMed

    Peugnet, Pauline; Robles, Morgane; Wimel, Laurence; Tarrade, Anne; Chavatte-Palmer, Pascale

    2016-07-01

    The study of early developmental conditioning of health and disease in adulthood is particularly relevant in the horse, which is bred mainly to perform in demanding sport challenges. On the basis of this concept, the management of the broodmare could be considered an effective means to produce animals with the desired features. Knowledge on the Developmental Origins of Health and Disease in the equine species remains relatively scarce, with some experimental studies and one single epidemiologic study. Data highlight the determinant role of the maternal environment for postnatal body conformation, immune response, energy homeostasis, osteoarticular status and thyroidal, adrenocortical, and cardiovascular functions of the foal. Most research, however, focuses on the first months/years after birth. Long-term effects on the adult horse phenotype have not been investigated so far. PMID:26954944

  12. Maternal complement C1q and increased odds for psychosis in adult offspring

    PubMed Central

    Severance, Emily G.; Gressitt, Kristin L.; Buka, Stephen L.; Cannon, Tyrone D.; Yolken, Robert H.

    2014-01-01

    The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race and gender, with further matching based on mother’s age. IgG markers of C1q, bovine milk casein, egg ovalbumin and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources. PMID:25195065

  13. Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet

    PubMed Central

    Orellana, Juan A.; Busso, Dolores; Ramírez, Gigliola; Campos, Marlys; Rigotti, Attilio; Eugenín, Jaime; von Bernhardi, Rommy

    2014-01-01

    Nicotine, the most important neuroteratogen of tobacco smoke, can reproduce brain and cognitive disturbances per se when administered prenatally. However, it is still unknown if paracrine signaling among brain cells participates in prenatal nicotine-induced brain impairment of adult offspring. Paracrine signaling is partly mediated by unopposed channels formed by connexins hemichannels (HCs) and pannexins serving as aqueous pores permeable to ions and small signaling molecules, allowing exchange between the intra- and extracellular milieus. Our aim was to address whether prenatal nicotine exposure changes the activity of those channels in adult mice offspring under control conditions or subjected to a second challenge during young ages: high-fat/cholesterol (HFC) diet. To induce prenatal exposure to nicotine, osmotic minipumps were implanted in CF1 pregnant mice at gestational day 5 to deliver nicotine bitartrate or saline (control) solutions. After weaning, offspring of nicotine-treated or untreated pregnant mice were fed ad libitum with chow or HFC diets for 8 weeks. The functional state of connexin 43 (Cx43) and pannexin 1 (Panx1) unopposed channels was evaluated by dye uptake experiments in hippocampal slices from 11-week-old mice. We found that prenatal nicotine increased the opening of Cx43 HCs in astrocytes, and Panx1 channels in microglia and neurons only if offspring mice were fed with HFC diet. Blockade of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2) and prostaglandin E receptor 1 (EP1), ionotropic ATP receptor type 7 (P2X7) and NMDA receptors, showed differential inhibition of prenatal nicotine-induced channel opening in glial cells and neurons. Importantly, inhibition of the above mentioned enzymes and receptors, or blockade of Cx43 and Panx1 unopposed channels greatly reduced adenosine triphosphate (ATP) and glutamate release from hippocampal slices of prenatally nicotine-exposed offspring. We propose that unregulated gliotransmitter

  14. The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress.

    PubMed

    Nascimento, Luciana; Freitas, Cristiane M; Silva-Filho, Reginaldo; Leite, Ana Catarina R; Silva, Alessandra B; da Silva, Aline Isabel; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; Maia, Maria Bernadete Souza; Fernandes, Mariana P; Lagranha, Claudia

    2014-08-01

    Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at -80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood. PMID:24905448

  15. Multigenerational effects of parental prenatal exposure to famine on adult offspring cognitive function

    PubMed Central

    Li, Jie; Na, Lixin; Ma, Hao; Zhang, Zhe; Li, Tianjiao; Lin, Liqun; Li, Qiang; Sun, Changhao; Li, Ying

    2015-01-01

    The effects of prenatal nutrition on adult cognitive function have been reported for one generation. However, human evidence for multigenerational effects is lacking. We examined whether prenatal exposure to the Chinese famine of 1959–61 affects adult cognitive function in two consecutive generations. In this retrospective family cohort study, we investigated 1062 families consisting of 2124 parents and 1215 offspring. We assessed parental and offspring cognitive performance by means of a comprehensive test battery. Generalized linear regression model analysis in the parental generation showed that prenatal exposure to famine was associated with a 8.1 (95% CI 5.8 to 10.4) second increase in trail making test part A, a 7.0 (1.5 to 12.5) second increase in trail making test part B, and a 5.5 (−7.3 to −3.7) score decrease in the Stroop color-word test in adulthood, after adjustment for potential confounders. In the offspring generation, linear mixed model analysis found no significant association between parental prenatal exposure to famine and offspring cognitive function in adulthood after adjustment for potential confounders. In conclusion, prenatal exposure to severe malnutrition is negatively associated with visual- motor skill, mental flexibility, and selective attention in adulthood. However, these associations are limited to only one generation. PMID:26333696

  16. Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

    PubMed

    Fujiwara, S; Suyama, A; Cologne, J B; Akahoshi, M; Yamada, M; Suzuki, G; Koyama, K; Takahashi, N; Kasagi, E; Grant, E J; Lagarde, E; Hsu, W L; Furukawa, K; Ohishi, W; Tatsukawa, Y; Neriishi, K; Takahashi, I; Ashizawa, K; Hida, A; Imaizumi, M; Nagano, J; Cullings, H M; Katayama, H; Ross, N P; Kodama, K; Shore, R E

    2008-10-01

    The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure. PMID:19024652

  17. Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring

    PubMed Central

    Lacy, Ryan T.; Hord, Lauren L.; Morgan, Amanda J.; Harrod, Steven B.

    2012-01-01

    Background Prenatal tobacco smoke exposure is associated with alterations in motivated behavior in offspring, such as increased consumption of highly palatable foods and abused drugs. Animal models show that gestational nicotine (GN) exposure mediates changes in responding for sucrose and drug reward. Methods A novel, intermittent low-dose intravenous (IV) exposure model was used to administer nicotine (0.05 mg/kg/injection) or saline 3×/day to rats on gestational days 8-21. Two experiments investigated the effect of IV GN on 1) the habituation of spontaneous locomotor activity and on 2) sucrose reinforced responding in offspring. For the operant experiments, animals acquired fixed-ratio (FR-3) responding for sucrose, 26% (w/v), and were tested on varying concentrations (0, 3, 10, 30, 56%; Latin-square) according to a FR-3, and then a progressive-ratio (PR) schedule. Male and female adult offspring were used. Results IV GN did not alter birth or growth weight, or the number of pups born. No between-group differences in habituation to spontaneous locomotor activity were observed. FR testing produced an inverted U-shaped response curve, and rats showed peak responding for 10% sucrose reinforcement. Neither gestation nor sex affected responding, suggesting equivalent sensitivity to varying sucrose concentrations. PR testing revealed that GN rats showed greater motivation for sucrose reinforcement relative to controls. Conclusions A low-dose, IV GN exposure model resulted in increased motivation to respond for sucrose reinforcement in adult offspring. This suggests that using a low number of cigarettes throughout pregnancy will result in increased motivation for highly palatable foods in adult, and perhaps, adolescent offspring. PMID:22377090

  18. Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

    PubMed Central

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J.; Poston, Lucilla; Taylor, Paul D.

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID:22043281

  19. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    PubMed

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J; Poston, Lucilla; Taylor, Paul D

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID:22043281

  20. Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring.

    PubMed

    Allina, Jorge; Grabowski, Jacquelin; Doherty-Lyons, Shannon; Fiel, M Isabel; Jackson, Christine E; Zelikoff, Judith T; Odin, Joseph A

    2011-01-01

    Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring. PMID:21718087

  1. Tobacco Smoking: Patterns, Health Consequences for Adults, and the Long-term Health of the Offspring

    PubMed Central

    Maritz, Gert S.; Mutemwa, Muyunda

    2012-01-01

    Tobacco use started several centuries ago and increased markedly after the invention of the cigarette making machine. Once people start smoking they find it difficult to quit the habit. This is due to the addictive effect of nicotine in tobacco smoke. Various epidemiologic and laboratory studies clearly showed that smoking is associated with various diseases such as heart diseases, asthma and emphysema and the associated increase in morbidity and mortality of smokers. Several studies implicate nicotine as the causative factor in tobacco smoke. Apart from nicotine, various carcinogens also occur in tobacco smoke resulting in an increase in the incidence of cancer in smokers. While the smoking habit is decreasing in developed countries, tobacco use increases in the developing countries. Smoking prevalence is also highest in poor communities and amongst those with low education levels. It is important to note that, although ther is a decline in the number of smokers in the developed countries, there is a three to four decades lag between the peak in smoking prevalence and the subsequent peak in smoking related mortality. It has been shown that maternal smoking induces respiratory diseases in the offspring. There is also evidence that parental smoking may program the offspring to develop certain diseases later in life. Various studies showed that maternal nicotine exposure during pregnancy and lactation via tobacco smoke of nicotine replacement therapy (NRT), program the offspring to develop compromised lung structure later in life with the consequent compromised lung function. This implies that NRT is not an option to assist pregnant or lactating smokers to quit the habit. Even paternal smoking may have an adverse effect on the health of the offspring since it has been shown that 2nd and 3rd hand smoking have adverse health consequences for those exposed to it. PMID:22980343

  2. Altered Health Outcomes in Adult Offspring of Sprague Dawley and Wistar Rats Undernourished During Early or Late Pregnancy

    EPA Science Inventory

    Gestational undernutrition in humans can result in birth weight reductions (an indicator of a suboptimal intrauterine environment) and predisposition to adult disease in offspring including high blood pressure, insulin resistance, glucose intolerance, and obesity (key components ...

  3. Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

    PubMed

    Figueiredo, Mariana Sarto; da Conceição, Ellen Paula Santos; de Oliveira, Elaine; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar

    2015-10-14

    Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and adrenaline β2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11β-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11β-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during

  4. Maternal dietary loads of α-tocopherol depress protein kinase C signaling and synaptic plasticity in rat postnatal developing hippocampus and promote permanent deficits in adult offspring.

    PubMed

    Betti, Michele; Ambrogini, Patrizia; Minelli, Andrea; Floridi, Alessandro; Lattanzi, Davide; Ciuffoli, Stefano; Bucherelli, Corrado; Prospero, Emilia; Frontini, Andrea; Santarelli, Lory; Baldi, Elisabetta; Benetti, Fernando; Galli, Francesco; Cuppini, Riccardo

    2011-01-01

    Vitamin E (α-tocopherol) supplementation has been tested as prophylaxis against gestational disorders associated with oxidative damage. However, recent evidence showing that high maternal α-tocopherol intake can adversely affect offspring development raises concerns on the safety of vitamin E extradosages during pregnancy. Besides acting as an antioxidant, α-tocopherol depresses cell proliferation and modulates cell signaling through inhibiting protein kinase C (PKC), a kinase that is deeply involved in neural maturation and plasticity. Possible effects of α-tocopherol loads in the maturing brain, where PKC dysregulation is associated to developmental dysfunctions, are poorly known. Here, supranutritional doses of α-tocopherol were fed to pregnant and lactating dams to evaluate the effects on PKC signaling and morphofunctional maturation in offspring hippocampus. Results showed that maternal supplementation potentiates hippocampal α-tocopherol incorporation in offspring and leads to marked decrease of PKC phosphorylation throughout postnatal maturation, accompanied by reduced phosphorylation of growth-associated protein-43 and myristoylated alanine-rich C kinase substrate, two PKC substrates involved in neural development and plasticity. Although processes of neuronal maturation, synapse formation and targeting appeared unaffected, offspring of supplemented mothers displayed a marked reduction of long-term synaptic plasticity in juvenile hippocampus. Interestingly, this impairment persisted in adulthood, when a deficit in hippocampus-dependent, long-lasting spatial memory was also revealed. In conclusion, maternal supplementation with elevated doses of α-tocopherol can influence cell signaling and synaptic plasticity in developing hippocampus and promotes permanent adverse effects in adult offspring. The present results emphasize the need to evaluate the safety of supranutritional maternal intake of α-tocopherol in humans. PMID:20382010

  5. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    USGS Publications Warehouse

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

  6. The Effects of Breeding Protocol in C57BL/6J Mice on Adult Offspring Behaviour

    PubMed Central

    Foldi, Claire J.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2011-01-01

    Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10–12 days) and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH). The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM). Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI) of the acoustic startle response. We found that length of sire exposure (LSE) had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour. PMID:21448436

  7. Older maternal age is associated with depression, anxiety, and stress symptoms in young adult female offspring.

    PubMed

    Tearne, Jessica E; Robinson, Monique; Jacoby, Peter; Allen, Karina L; Cunningham, Nadia K; Li, Jianghong; McLean, Neil J

    2016-01-01

    The evidence regarding older parental age and incidence of mood disorder symptoms in offspring is limited, and that which exists is mixed. We sought to clarify these relationships by using data from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study provided comprehensive data from 2,900 pregnancies, resulting in 2,868 live born children. A total of 1,220 participants completed the short form of the Depression Anxiety Stress Scale (DASS-21) at the 20-year cohort follow-up. We used negative binomial regression analyses with log link and with adjustment for known perinatal risk factors to examine the extent to which maternal and paternal age at childbirth predicted continuous DASS-21 index scores. In the final multivariate models, a maternal age of 30-34 years was associated with significant increases in stress DASS-21 scores in female offspring relative to female offspring of 25- to 29-year-old mothers. A maternal age of 35 years and over was associated with increased scores on all DASS-21 scales in female offspring. Our results indicate that older maternal age is associated with depression, anxiety, and stress symptoms in young adult females. Further research into the mechanisms underpinning this relationship is needed. PMID:26569038

  8. Sex-specific increase in susceptibility to metabolic syndrome in adult offspring after prenatal ethanol exposure with post-weaning high-fat diet.

    PubMed

    He, Zheng; Li, Jing; Luo, Hanwen; Zhang, Li; Ma, Lu; Chen, Liaobin; Wang, Hui

    2015-01-01

    Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE. PMID:26631430

  9. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    PubMed Central

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. Methods To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. Results The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. Conclusions These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood. PMID:25642385

  10. Unlike pregnant adult women, pregnant adolescent girls cannot maintain glycine flux during late pregnancy because of decreased synthesis from serine.

    PubMed

    Hsu, Jean W; Thame, Minerva M; Gibson, Raquel; Baker, Tameka M; Tang, Grace J; Chacko, Shaji K; Jackson, Alan A; Jahoor, Farook

    2016-03-14

    During pregnancy, glycine and serine become more important because they are the primary suppliers of methyl groups for the synthesis of fetal DNA, and more glycine is required for fetal collagen synthesis as pregnancy progresses. In an earlier study, we reported that glycine flux decreased by 39% from the first to the third trimester in pregnant adolescent girls. As serine is a primary precursor for glycine synthesis, the objective of this study was to measure and compare glycine and serine fluxes and inter-conversions in pregnant adolescent girls and adult women in the first and third trimesters. Measurements were made after an overnight fast by continuous intravenous infusions of 2H2-glycine and 15N-serine in eleven adolescent girls (17·4 (se 0·1) years of age) and in ten adult women (25·8 (se 0·5) years of age) for 4 h. Adolescent girls had significantly slower glycine flux and they made less glycine from serine in the third (P<0·05) than in the first trimester. Baby birth length was significantly shorter of adolescent girls (P=0·04) and was significantly associated with third trimester glycine flux. These findings suggest that the pregnant adolescent cannot maintain glycine flux in late pregnancy compared with early pregnancy because of decreased synthesis from serine. It is possible that the inability to maintain glycine synthesis makes her fetus vulnerable to impaired cartilage synthesis, and thus linear growth. PMID:26785702

  11. Sleep fragmentation during late gestation induces metabolic perturbations and epigenetic changes in adiponectin gene expression in male adult offspring mice.

    PubMed

    Khalyfa, Abdelnaby; Mutskov, Vesco; Carreras, Alba; Khalyfa, Ahamed A; Hakim, Fahed; Gozal, David

    2014-10-01

    Sleep fragmentation (SF) is a common condition among pregnant women, particularly during late gestation. Gestational perturbations promote the emergence of adiposity and metabolic disease risk in offspring, most likely through epigenetic modifications. Adiponectin (AdipoQ) expression inversely correlates with obesity and insulin resistance. The effects of SF during late gestation on metabolic function and AdipoQ expression in visceral white adipose tissue (VWAT) of offspring mice are unknown. Male offspring mice were assessed at 24 weeks after dams were exposed to SF or control sleep during late gestation. Increased food intake, body weight, VWAT mass, and insulin resistance, with reductions in AdipoQ expression in VWAT, emerged in SF offspring. Increased DNMT3a and -b and global DNA methylation and reduced histone acetyltransferase activity and TET1, -2, and -3 expression were detected in VWAT of SF offspring. Reductions in 5-hydroxymethylcytosine and H3K4m3 and an increase in DNA 5-methylcytosine and H3K9m2 in the promoter and enhancer regions of AdipoQ emerged in adipocytes from VWAT and correlated with AdipoQ expression. SF during late gestation induces epigenetic modifications in AdipoQ in male offspring mouse VWAT adipocytes along with a metabolic syndrome-like phenotype. Thus, altered gestational environments elicited by SF impose the emergence of adverse, long-lasting metabolic consequences in the next generation. PMID:24812424

  12. Maternal Grand Multiparity and the Risk of Severe Mental Disorders in Adult Offspring

    PubMed Central

    Lahti, Marius; Eriksson, Johan G.; Heinonen, Kati; Kajantie, Eero; Lahti, Jari; Wahlbeck, Kristian; Tuovinen, Soile; Pesonen, Anu-Katriina; Mikkonen, Maiju; Osmond, Clive; Räikkönen, Katri

    2014-01-01

    Background Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life. Methods Our study sample comprised 13243 Helsinki Birth Cohort Study 1934–1944 participants (6905 men and 6338 women). According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969–2010. Results Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03), non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002), and suicide attempts (Hazard Ratio = 3.94, p = 0.01) in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01), non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02) schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02), mood disorders (Hazard Ratio = 2.40, p = 0.002), non-psychotic mood disorders (Hazard Ratio = 2.91, p<0.001), and suicide attempts (Hazard Ratio = 5.05, p = 0.01) in adulthood. The effects of maternal grand multiparity on offspring psychopathology risk were independent of maternal age and body mass index at childbirth, and of year of birth, sex, childhood socioeconomic position, and birth weight of the offspring. In contrast, no significant effects were found among men. Conclusions Women born to grand multiparous mothers are at an increased risk of severe mental disorders and suicide attempts across

  13. Transgenerational Effects of Parental Larval Diet on Offspring Development Time, Adult Body Size and Pathogen Resistance in Drosophila melanogaster

    PubMed Central

    Valtonen, Terhi M.; Kangassalo, Katariina; Pölkki, Mari; Rantala, Markus J.

    2012-01-01

    Environmental conditions experienced by parents are increasingly recognized to affect offspring performance. We set out to investigate the effect of parental larval diet on offspring development time, adult body size and adult resistance to the bacterium Serratia marcescens in Drosophila melanogaster. Flies for the parental generation were raised on either poor or standard diet and then mated in the four possible sex-by-parental diet crosses. Females that were raised on poor food produced larger offspring than females that were raised on standard food. Furthermore, male progeny sired by fathers that were raised on poor food were larger than male progeny sired by males raised on standard food. Development times were shortest for offspring whose one parent (mother or the father) was raised on standard and the other parent on poor food and longest for offspring whose parents both were raised on poor food. No evidence for transgenerational effects of parental diet on offspring disease resistance was found. Although paternal effects have been previously demonstrated in D. melanogaster, no earlier studies have investigated male-mediated transgenerational effects of diet in this species. The results highlight the importance of not only considering the relative contribution each parental sex has on progeny performance but also the combined effects that the two sexes may have on offspring performance. PMID:22359607

  14. Stress during first pregnancy increases seizure threshold in adult male offspring

    PubMed Central

    Pajand, Peyman; Elahdadi Salmani, Mahmoud; Shajiee, Hooman; Abiri, Hasan; Goudarzi, Iran; Abrari, Kataneh

    2014-01-01

    Objective(s): Stress induces many homeostatic aberrations which are followed by lifelong allostatic responses. Epilepsy is developed or influenced by different environmental factors, i.e. prenatal stress which makes many contradictory developmental changes in seizure threshold and intensity. We investigated the potential seizure response of the rat offspring to prenatal stress; the stress which was applied to their mothers. Materials and Methods: Nine day heterogeneous sequential stress (HSS) model was used before and during the first and before the second pregnancy. The kindling was induced using 13 IP injections of pentylenetetrazol (PTZ) every 48 hr to adult male Wistar rat's offspring. Results: The results of the present study demonstrated that, before pregnancy stress decreased the rate of kindling (P<0.05) in the offspring, while stress which was applied during pregnancy completely prevented kindling (P <0.001). Further, their convulsive latency was increased and tonic clonic seizure duration was decreased. In contrast, previous pregnancy and between pregnancies stress could not change kindling process. Although maternal separation stress did not change kindling development, it could increase convulsive intensities by elongating the duration of seizures (P<0.05) and reducing convulsion latency (P <0.05). Conclusion: It is concluded that stress detrimental effects could be prevented by stress which was applied around first pregnancy; however this beneficial effect is weakened by before second pregnancy stress. PMID:24592305

  15. The association of maternal socialization in childhood and adolescence with adult offsprings' sympathy/caring.

    PubMed

    Eisenberg, Nancy; VanSchyndel, Sarah K; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood (between 7-8 and 11-12 years of age) and adolescence (between 13-14 and 17-18 years of age). Adult offsprings' sympathy/caring was assessed 3 times in early adulthood (at ages 19-20 to 23-24 years) and in their mid-20s to 30s (ages 25-26 to 31-32 years). In general, friends' reports of participants' sympathy/concern at ages 25-32 years related positively to mother-reported rational discipline (including inductions) and warmth and support during childhood and adolescence and negatively to mother-reported negative affect during adolescence. Self-reported sympathy/concern during early adulthood was positively related to maternal warmth and support during childhood and almost significantly negatively related to mother-reported negative affect during childhood and adolescence. Most of the relations held when the prior level of self-reported childhood empathy or adolescent sympathy was controlled. PMID:25383690

  16. Childhood maltreatment in adult offspring of Portuguese war veterans with and without PTSD

    PubMed Central

    Dias, Aida; Sales, Luisa; Cardoso, Rui M.; Kleber, Rolf

    2014-01-01

    Background The colonial war that Portugal was involved in between 1961 and 1974 had a significant impact on veterans and their families. However, it is unclear what the consequences of this war are, in particular with regard to levels of childhood maltreatment (CM) in offspring. Objective Our study aims to analyze the influences of fathers’ war exposure and posttraumatic stress disorder (PTSD) on the offspring's CM and simultaneously test the hypothesis of the intergenerational transmission of father–child CM. Method Cross-sectional data were collected, using the Childhood Trauma Questionnaire—Short Form, from 203 adult children and 117 fathers. Subjects were distributed according to three conditions based on the father's war exposure status: did not participate in war, or non-war-exposed (NW); participated in war, or war-exposed (W); and war-exposed with PTSD diagnosis (WP). The data were examined using correlations, variance/covariance, and regression analyses. Results Children of war veterans with PTSD reported more emotional and physical neglect, while their fathers reported increased emotional and physical abuse exposure during their own childhood. Significant father–child CM correlations were found in the war veteran group but less in the war veteran with PTSD group. Father CM predicted 16% of offspring CM of children of war veterans. Conclusions The father's war-related PTSD might be a risk factor for offspring neglect but potentially a protective one for the father–child abuse transmission. War-exposed fathers without PTSD did transmit their own CM experiences more often. Therefore, father's war exposure and father's war PTSD may each be important variables to take into account in the study of intergenerational transmission of CM. PMID:24505510

  17. MATERNAL EXPERIENCE OF ABUSE IN CHILDHOOD AND DEPRESSIVE SYMPTOMS IN ADOLESCENT AND ADULT OFFSPRING: A 21-YEAR LONGITUDINAL STUDY

    PubMed Central

    Roberts, Andrea L.; Chen, Ying; Slopen, Natalie; McLaughlin, Katie A.; Koenen, Karestan C.; Austin, Sydney Bryn

    2015-01-01

    Background Intergenerational effects of child abuse have been documented, but it is unknown whether maternal childhood abuse influences offspring mental health in adolescence or adulthood. Methods To examine whether maternal experience of childhood abuse is associated with depressive symptoms in adolescent and young adult offspring, we linked data from two large longitudinal cohorts of women (N = 8,882) and their offspring (N = 11,402), and we examined three possible pathways by which maternal experience of abuse might be associated with offspring depressive symptoms: maternal mental health, family characteristics, and offspring’s own experience of abuse. Results Offspring of women who experienced severe versus no childhood abuse had greater likelihood of high depressive symptoms (RR = 1.78, 95% CI = 1.47, 2.16) and persistent high depressive symptoms (RR = 2.47, 95% CI = 1.37, 4.44). Maternal mental health accounted for 20.9% and offspring’s exposure to abuse accounted for 30.3% of the elevated risk of high depressive symptoms. Disparities in offspring depressive symptoms by maternal abuse exposure were evident at age 12 years and persisted through age 31 years. Conclusions Findings provide evidence that childhood abuse adversely affects the mental health of the victim’s offspring well into adulthood. As offspring exposure to abuse and maternal mental health accounted for more than 50% of the elevated risk of high depressive symptoms among offspring of women who experienced abuse, improving maternal mental health and parenting practices may reduce offspring risk for depressive symptoms in these families. PMID:26220852

  18. Perinatal Taurine Alters Arterial Pressure Control and Renal Function in Adult Offspring

    PubMed Central

    Roysommuti, Sanya; Lerdweeraphon, Wichaporn; Malila, Pisamai; Jirakulsomchok, Dusit; Wyss, J. Michael

    2009-01-01

    The present study investigates the effect of perinatal taurine exposure on renal function in adult, female rats on a high sugar diet. Perinatal taurine depleted (TD), supplemented (TS) or untreated control (C) female offspring were fed normal rat chow and tap water (CW,TDW or TSW) or tap water with 5% glucose (CG, TDG or TSG) after weaning. At 7–8 weeks of age, renal function was studied in the conscious, restrained rats. Mean arterial pressure was significantly higher in TDW, TDG, and TSG rats. Plasma sodium concentration was significantly lower in all glucose treated animals, but the greatest decrease was in TDW rats. Basal renal blood flow was lowest in TSW and TSG, and the responses to a saline load were also lowest in those two groups. These changes were consistent with increased renal vascular resistance. The basal glomerular filtration rate was lowest in TSW, but the responses to a saline load were similar in all of the groups. Water excretion was lower in TSG and TSW, consistent with increased renal tubular water reabsorption. These data suggest that perinatal taurine exposure alters normal renal function and renal responses to dietary sugar in adult female offspring. PMID:19239145

  19. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  20. Adult and offspring size in the ocean over 17 orders of magnitude follows two life history strategies.

    PubMed

    Neuheimer, A B; Hartvig, M; Heuschele, J; Hylander, S; Kiørboe, T; Olsson, K H; Sainmont, J; Andersen, K H

    2015-12-01

    Explaining variability in offspring vs. adult size among groups is a necessary step to determine the evolutionary and environmental constraints shaping variability in life history strategies. This is of particular interest for life in the ocean where a diversity of offspring development strategies is observed along with variability in physical and biological forcing factors in space and time. We compiled adult and offspring size for 407 pelagic marine species covering more than 17 orders of magnitude in body mass including Cephalopoda, Cnidaria, Crustaceans, Ctenophora, Elasmobranchii, Mammalia, Sagittoidea, and Teleost. We find marine life following one of two distinct strategies, with offspring size being either proportional to adult size (e.g., Crustaceans, Elasmobranchii, and Mammalia) or invariant with adult size (e.g., Cephalopoda, Cnidaria, Sagittoidea, Teleosts, and possibly Ctenophora). We discuss where these two strategies occur and how these patterns (along with the relative size of the offspring) may be shaped by physical and biological constraints in the organism's environment. This adaptive environment along with the evolutionary history of the different groups shape observed life history strategies and possible group-specific responses to changing environmental conditions (e.g., production and distribution). PMID:26909435

  1. Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring

    PubMed Central

    Beauchamp, Brittany; Thrush, A. Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y.; Patti, Mary-Elizabeth; Harper, Mary-Ellen

    2015-01-01

    Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. PMID:26182362

  2. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  3. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  4. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  5. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  6. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  7. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  8. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  9. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults. 26.1704 Section 26.1704 Protection of Environment... research with non-pregnant, non-nursing adults. (a) This section applies to research subject to...

  10. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  11. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults. 26.1704 Section 26.1704 Protection of Environment... research with non-pregnant, non-nursing adults. (a) This section applies to research subject to...

  12. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. PMID:26844865

  13. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  14. Timing of antenatal care for adolescent and adult pregnant women in south-eastern Tanzania

    PubMed Central

    2012-01-01

    Background Early and frequent antenatal care attendance during pregnancy is important to identify and mitigate risk factors in pregnancy and to encourage women to have a skilled attendant at childbirth. However, many pregnant women in sub-Saharan Africa start antenatal care attendance late, particularly adolescent pregnant women. Therefore they do not fully benefit from its preventive and curative services. This study assesses the timing of adult and adolescent pregnant women's first antenatal care visit and identifies factors influencing early and late attendance. Methods The study was conducted in the Ulanga and Kilombero rural Demographic Surveillance area in south-eastern Tanzania in 2008. Qualitative exploratory studies informed the design of a structured questionnaire. A total of 440 women who attended antenatal care participated in exit interviews. Socio-demographic, social, perception- and service related factors were analysed for associations with timing of antenatal care initiation using regression analysis. Results The majority of pregnant women initiated antenatal care attendance with an average of 5 gestational months. Belonging to the Sukuma ethnic group compared to other ethnic groups such as the Pogoro, Mhehe, Mgindo and others, perceived poor quality of care, late recognition of pregnancy and not being supported by the husband or partner were identified as factors associated with a later antenatal care enrolment (p < 0.05). Primiparity and previous experience of a miscarriage or stillbirth were associated with an earlier antenatal care attendance (p < 0.05). Adolescent pregnant women started antenatal care no later than adult pregnant women despite being more likely to be single. Conclusions Factors including poor quality of care, lack of awareness about the health benefit of antenatal care, late recognition of pregnancy, and social and economic factors may influence timing of antenatal care. Community-based interventions are needed that involve

  15. High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring.

    PubMed

    Kruse, Michael; Keyhani-Nejad, Farnaz; Isken, Frank; Nitz, Barbara; Kretschmer, Anja; Reischl, Eva; de las Heras Gala, Tonia; Osterhoff, Martin A; Grallert, Harald; Pfeiffer, Andreas F H

    2016-03-01

    Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming. PMID:26631738

  16. Residual effects of polychlorinated biphenyls on adult nonhuman primates and their offspring

    SciTech Connect

    Allen, J.R.; Barsotti, D.A.; Carstens, L.A.

    1980-01-01

    After 18 months of consuming a diet containing 2.5 and 5.0 ppM PCB (Aroclor 1248), during which they and their offspring experienced marked alterations in physical status, female rhesus monkeys were placed on a control diet for 1 y. During this year there was a decided improvement in their general body health and reproductive capabilities. Infants born to these animals were small at birth and during their postnatal life developed signs of PCB intoxication similar to those observed in their siblings born during the period of PCB exposure. These data indicate that the residual effects of low-level ingestion of PCBs by nonhuman primates persist for over 1 y after discontinuation of exposure. There are also indications that the fetal and neonatal monkeys born to PCB-exposed mothers are more severely affected for a longer period than are the adult female monkeys.

  17. Pathogenesis and epidemiology of Brucellosis in Yellowstone bison: serologic and culture results from adult females and their offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this prospective study was to follow the natural course of Brucella abortus infection in cohorts of seropositive and seronegative female bison and their offspring in Yellowstone National Park over a 5 year period. Specimens were collected from 53 adult, female bison at least once a...

  18. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

    EPA Science Inventory

    Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the bi...

  19. Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

    PubMed

    Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders. PMID:26383033

  20. A dose-response relationship between maternal smoking during late pregnancy and adult intelligence in male offspring.

    PubMed

    Mortensen, Erik Lykke; Michaelsen, Kim Fleischer; Sanders, Stephanie A; Reinisch, June Machover

    2005-01-01

    An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Borge Priens Prove) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates. Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P=0.0001). The mean difference between the no-smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P=0.007). Both unadjusted and adjusted means suggested a dose-response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n=1829). These results suggest that smoking during pregnancy may have long-term negative consequences on offspring adult intelligence. PMID:15670102

  1. Association between parental psychopathology and suicidal behavior among adult offspring: results from the cross-sectional South African Stress and Health survey

    PubMed Central

    2014-01-01

    Background Prior studies have demonstrated a link between parental psychopathology and offspring suicidal behavior. However, it remains unclear what aspects of suicidal behavior among adult offspring are predicted by specific parental mental disorders, especially in Africa. This study set out to investigate the association between parental psychopathology and suicidal behavior among their adult offspring in a South African general population sample. Method Parental psychopathology and suicidal behavior in offspring were assessed using structured interviews among 4,315 respondents from across South Africa. The WHO CIDI was used to collect data on suicidal behavior, while the Family History Research Diagnostic Criteria Interview was used to assess prior parental psychopathology. Bivariate and multivariate survival models tested the associations between the type and number parental mental disorders (including suicide) and lifetime suicidal behavior in the offspring. Associations between a range of parental disorders and the onset of subsequent suicidal behavior (suicidal ideation, plans, and attempts) among adult offspring were tested. Results The presence of parental psychopathology significantly increased the odds of suicidal behavior among their adult offspring. More specifically, parental panic disorder was associated with offspring suicidal ideation, while parental panic disorder, generalized anxiety disorder and suicide were significantly associated with offspring suicide attempts. Among those with suicidal ideation, none of the tested forms of parental psychopathology was associated with having suicide plans or attempts. There was a dose–response relationship between the number of parental disorders and odds of suicidal ideation. Conclusions Parental psychopathology increases the odds of suicidal behavior among their adult offspring in the South African context, replicating results found in other regions. Specific parental disorders predicted the onset and

  2. Prenatal nicotine exposure induces poor articular cartilage quality in female adult offspring fed a high-fat diet and the intrauterine programming mechanisms.

    PubMed

    Tie, Kai; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2016-04-01

    Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism. PMID:26769161

  3. Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring

    PubMed Central

    Bader, Heather N.; Bierer, Linda M.; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

    2014-01-01

    Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 h urinary cortisol was assayed by RIA. Offspring completed the parental PTSD questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence, or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusion: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased

  4. Association study between reward dependence and a functional BDNF polymorphism in adult women offspring of alcohol-dependent probands.

    PubMed

    Benzerouk, Farid; Gierski, Fabien; Raucher-Chéné, Delphine; Ramoz, Nicolas; Gorwood, Philip; Kaladjian, Arthur; Limosin, Frédéric

    2015-10-01

    Thirty-five healthy adult women offspring of alcohol-dependent probands (AWOA) were compared with 63 healthy controls to test whether personality dimensions on the Temperament and Character Inventory questionnaire were associated with the brain-derived neurotrophic factor Val66Met polymorphism in offspring. We found a significantly lower reward dependence score in AWOA compared with the controls. The brain-derived neurotrophic factor Val66Met polymorphism may be involved in this difference as the lower reward dependence score was found only in AWOA carrying the Val allele. PMID:26204172

  5. The influence of parental divorce and alcohol abuse on adult offspring risk of lifetime suicide attempt in the United States.

    PubMed

    Alonzo, Dana; Thompson, Ronald G; Stohl, Mahlki; Hasin, Deborah

    2014-05-01

    The influences of parental divorce and alcohol abuse on adult offspring lifetime suicide attempt have not been examined in national data. This study analyzed data from the 2001-2002 NESARC to estimate main and interaction effects of parental divorce and alcohol abuse on lifetime suicide attempt. Adjusted for controls, parental divorce and parental alcohol abuse independently increased odds of lifetime suicide attempt. The effect of parental divorce was not significantly moderated by parental alcohol abuse. Further research is needed to examine whether additional parental and offspring psychiatric and substance use covariates attenuate the association between parental divorce and lifetime suicide attempt. PMID:24827026

  6. Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

    PubMed Central

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R.; Newman, John W.; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring. PMID:25076055

  7. Hypoxia in early pregnancy induces cardiac dysfunction in adult offspring of Rattus norvegicus, a non-hypoxia-adapted species.

    PubMed

    Hauton, David

    2012-11-01

    Environmental stresses such as hypoxia can alter the development of the fetus that are manifested later in life, but the impact of early maternal hypoxia (MH) on cardiac performance, coronary flow and catecholamine responsiveness in adult offspring is less clear. The effects of exposure to chronic hypoxia (FIO(2)=0.12) in early intrauterine development (days E1-10) on cardiac performance of the adult offspring were estimated using the Langendorff-perfused rat heart. Cardiac dysfunction is presented as increased end-diastolic volume, with decreased ventricular stiffness in both male and female adult offspring (P<0.01 for both). While developed pressures were preserved in female MH rats, males demonstrated a decrease in systolic function, estimated as peak developed pressure (P<0.01). Challenge with dobutamine (300 nM), an adrenergic positive inotrope, increased cardiac work for control rats (P<0.01 for male and female rats) but not in MH-male rats. Coronary flow was reduced (P<0.01) and SERCA2 protein expression increased (2-fold, P<0.05) in female offspring, while eNOS protein levels were increased (2.5-fold, P<0.05) in females. This suggests gender-specific differences in compensatory responses to early MH, with female rats increasing calcium turnover to improve contractility and increasing coronary flow through increased expression of eNOS protein, partially restoring coronary perfusion while male rats show little compensation. PMID:22892476

  8. Liquid fructose in pregnancy exacerbates fructose-induced dyslipidemia in adult female offspring.

    PubMed

    Rodríguez, Lourdes; Panadero, María I; Rodrigo, Silvia; Roglans, Núria; Otero, Paola; Álvarez-Millán, Juan J; Laguna, Juan C; Bocos, Carlos

    2016-06-01

    Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and related events. Nevertheless, consumption of beverages sweetened with fructose is not regulated in gestation. Previously, we found that maternal fructose intake produces in the progeny, when fetuses, impaired leptin signaling and hepatic steatosis and then impaired insulin signaling and hypoadiponectinemia in adult male rats. Interestingly, adult females from fructose-fed mothers did not exhibit any of these disturbances. However, we think that, actually, these animals keep a programmed phenotype hidden. Fed 240-day-old female progeny from control, fructose- and glucose-fed mothers were subjected for 3weeks to a fructose supplementation period (10% wt/vol in drinking water). Fructose intake provoked elevations in insulinemia and adiponectinemia in the female progeny independently of their maternal diet. In accordance, the hepatic mRNA levels of several insulin-responsive genes were similarly affected in the progeny after fructose intake. Interestingly, adult progeny of fructose-fed mothers displayed, in response to the fructose feeding, augmented plasma triglyceride and NEFA levels and hepatic steatosis versus the other two groups. In agreement, the expression and activity for carbohydrate response element binding protein (ChREBP), a lipogenic transcription factor, were higher after the fructose period in female descendants from fructose-fed mothers than in the other groups. Furthermore, liver fructokinase expression that has been indicated as one of those responsible for the deleterious effects of fructose ingestion was preferentially augmented in that group. Maternal fructose intake does influence the adult female offspring's response to liquid fructose and so exacerbates fructose-induced dyslipidemia and hepatic steatosis. PMID:27142744

  9. Maternal high-fat diet inversely affects insulin sensitivity in dams and young adult male rat offspring.

    PubMed

    Karbaschi, Roxana; Sadeghimahalli, Forouzan; Zardooz, Homeira

    2016-09-01

    This study attempts to further clarify the potential effects of maternal high-fat (HF) diet on glucose homeostasis in dams and young adult male rat offspring. Female rats were divided into control (CON dams) and HF (HF dams) diet groups, which received the diet 4 weeks prior to and through pregnancy and lactation periods. Blood samples were taken to determine metabolic parameters, then an intraperitoneal glucose tolerance test (IPGTT) was performed. Maternal HF diet increased intra-abdominal fat mass and plasma corticosterone level, but decreased leptin concentration in dams. In HF offspring intra-abdominal fat mass, plasma leptin, and corticosterone levels decreased. Following IPGTT, the plasma insulin level of HF dams was higher than the controls. In HF offspring plasma insulin level was not significantly different from the controls, but a steeper decrease of their plasma glucose concentration was observed. PMID:27604865

  10. Effects of a preventive parenting intervention for divorced families on the intergenerational transmission of parenting attitudes in young adult offspring.

    PubMed

    Mahrer, Nicole E; Winslow, Emily; Wolchik, Sharlene A; Tein, Jenn-Yun; Sandler, Irwin N

    2014-01-01

    This study evaluates whether the New Beginnings Program (NBP), a parenting intervention for divorced mothers, led to positive parenting attitudes in young adult offspring. Data were collected from 240 mothers (G1) and offspring (G2) at ages 9-12 and again in adolescence and young adulthood. Alternative theoretical models were tested to examine mediators of NBP effects on G2 parenting attitudes. Significant interactions between condition and baseline G1 parenting indicated that NBP improved G2's parenting attitudes for those exposed to poorer G1 parenting at program entry. Effects on G2 warm attitudes were partially mediated through program effects on G1 warm parenting. The implications of improving parenting attitudes in offspring who experience parental divorce on well-being in the next generation are discussed. PMID:24916511

  11. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  12. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    SciTech Connect

    Wang, Lingxing; Cai, Ruowei; Lv, Guorong; Huang, Ziyang; Wang, Zhenhua

    2010-05-28

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  13. HIV-Infected Adolescent, Young Adult and Pregnant Smokers: Important Targets for Effective Tobacco Control Programs

    PubMed Central

    Escota, Gerome; Önen, Nur

    2013-01-01

    Tobacco use is inextricably linked to a number of health risks both in the general and HIV-infected populations. There is, however, a dearth of research on effective tobacco control programs among people living with HIV, and especially among adolescents, young adults and pregnant women, groups with heightened or increased vulnerability secondary to tobacco use. Adolescents and young adults constitute a growing population of persons living with HIV infection. Early and continued tobacco use in this population living with a disease characterized by premature onset multimorbidity and chronic inflammation is of concern. Additionally, there is an increased acuity for tobacco control among HIV-infected pregnant women to reduce pregnancy morbidity and improve fetal outcome. This review will provide an important summary of current knowledge of tobacco use among HIV-infected adolescents, young adults and pregnant women. The effects of tobacco use in these specific populations will be presented and the current state of tobacco control within these populations, assessed. PMID:23778059

  14. Mortality in Adult Offspring of Immigrants: A Swedish National Cohort Study

    PubMed Central

    Manhica, Hélio; Toivanen, Susanna; Hjern, Anders; Rostila, Mikael

    2015-01-01

    Background Higher risks of psychiatric disorders and lower-than-average subjective health in adulthood have been demonstrated in offspring of immigrants in Sweden compared with offspring of native Swedes, and linked to relative socioeconomic disadvantage. The present study investigated mortality rates in relation to this inequity from a gender perspective. Methods We used data from national registers covering the entire Swedish population aged 18-65 years. Offspring of foreign-born parents who were either Swedish born or had received residency in Sweden before school age (<7 years) were defined as “offspring of immigrants.” We used Cox regression models to examine the association between parental country of birth and mortality between 1990 and 2008, with adjustment for education, income, age and family type. Results Male offspring of immigrants from the Middle East (HR:2.00, CI:1.66-2.26), other non-European countries (HR:1.80, CI:1.36-2.36) and Finland (HR:1.56, CI:1.48-1.65) showed an age-adjusted excess mortality risk from all causes of death when compared to offspring with Swedish-born parents. Income, but not education, greatly attenuated these increased mortality risks. No excess mortality rates were found among female offspring of immigrants, with the exception of external cause of death among offspring of Finnish immigrants. Conclusion The study demonstrates high mortality rates in male offspring of immigrants from Finland and non-European countries that are associated with economic, but not educational, disadvantage. No increased mortality rates were found among female offspring of immigrants. Future studies are needed to explain this gender differential and why income, but not education, predicts mortality in male offspring of immigrants. PMID:25706297

  15. Parental Midlife Body Shape and Association with Multiple Adult Offspring Obesity Measures: North West Adelaide Health Study

    PubMed Central

    2015-01-01

    There is compelling evidence that parental weight is a strong determinant of offspring weight status. The study used cross-sectional self-reported and measured data from a longitudinal cohort of Australian adults (n = 2128) from Stage 3 (2008–10) of the North West Adelaide Health Study (1999–2003, baseline n = 4056) to investigate the association between midlife parental body shape and four indicators of obesity and fat distribution. The analysis used measured body mass index (BMI), waist circumference (WC), waist hip ratio (WHR) and waist height ratio (WHtR) of adult offspring, together with pictograms for recall of parental body shape. Compared to both parents being a healthy weight, offspring were more likely to be overweight or obese if both parents were an unhealthy weight at age 40 (OR 2.14, 95% CI 1.67–2.76) and further, those participants whose mother was an unhealthy weight were more likely to be overweight or obese themselves (OR 1.50, 95% CI 1.14–1.98). There were similar but lower results for those with an overweight/obese father (OR 1.44, 95% CI 1.08–1.93). The effect of one or both parents being overweight or obese tended to be stronger for daughters than for sons across BMI, WC and WHtR. BMI showed the strongest association with parental body shape (OR 2.14), followed by WC (OR 1.78), WHtR (OR 1.71) and WHR (OR 1.45). WHtR (42–45%) and BMI (35–36%) provided the highest positive predictive values for overweight/obesity from parental body shape. Parental obesity increases the risk of obesity for adult offspring, both for overall body shape and central adiposity, particularly for daughters. Pictograms could potentially be used as a screening tool in primary care settings to promote healthy weight among young adults. PMID:26355742

  16. Epigenetics: Behavioral Influences on Gene Function, Part I: Maternal Behavior Permanently Affects Adult Behavior in Offspring

    ERIC Educational Resources Information Center

    Ogren, Marilee P.; Lombroso, Paul J.

    2008-01-01

    The article highlights the field of epigenetics and its relevance in determining the effects of maternal nurturing on behavioral patterns in offsprings. Results concluded that maternal behavior influences the offspring's behavior to stress in adulthood and the effects are transgenerational through epigenetic mechanisms.

  17. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming". PMID:24275070

  18. Adult exposure to the synthetic hormone 17α-ethynylestradiol affects offspring of the gastropods Nassarius burchardi and Nassarius jonasii.

    PubMed

    Borysko, Larissa; Ross, Pauline M

    2014-05-01

    The aim of this study was to determine whether adult exposure to endocrine disrupting compounds affects offspring using trans-generational testing. Adult estuarine dwelling gastropods Nassarius burchardi and Nassarius jonasii were exposed to the synthetic estrogen 17α-ethynylestradiol (EE2) to determine the effects on the development and survival of their offspring. Adults were maintained in synthetic seawater controls and EE2 treatments (0.005, 0.05, 0.5, 50µg/L) over a sixteen week period. Egg capsules were collected from the adults following four, ten and sixteen weeks of adult exposure and transferred to different EE2 exposure scenarios. Treatment concentrations were selected to represent changes in EE2 exposure that could occur over different periods in an organism's lifecycle. Egg capsules laid by adults were therefore transferred to control or EE2 treatments (0.005, 0.05, 0.5, 5, 50, 500µg/L) to develop until hatching. The percentage of egg capsules with unviable eggs and abnormalities, number of days for hatching to occur and hatching success were measured. The veliger larvae that hatched from egg capsules following two, eight and fourteen weeks of adult exposure to EE2 and controls were used in 96h acute toxicity tests with controls and EE2 treatments at concentrations of 0.5, 5, 50, 500, 1250, 2500, 4000µg/L. Exposure of adult N. burchardi and N. jonasii to EE2 affected the percentage of egg capsules with unviable eggs, the development and hatching success of embryos and survival of veligers. These toxicity tests produced a complex set of results with different responses in developing eggs and veliger larvae to the adult EE2 treatments and length of adult exposure. This study demonstrates the importance of trans-generational testing and adult exposure scenarios in toxicity investigations. PMID:24462525

  19. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring.

    PubMed

    Dahlhoff, M; Pfister, S; Blutke, A; Rozman, J; Klingenspor, M; Deutsch, M J; Rathkolb, B; Fink, B; Gimpfl, M; Hrabě de Angelis, M; Roscher, A A; Wolf, E; Ensenauer, R

    2014-02-01

    Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized Naval Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features were not observed in females. Instead, they showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet∗sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition. PMID:24275555

  20. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure.

    PubMed

    Nobre, J L; Lisboa, P C; Santos-Silva, A P; Lima, N S; Manhães, A C; Nogueira-Neto, J F; Cabanelas, A; Pazos-Moura, C C; Moura, E G; de Oliveira, E

    2011-09-01

    Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action. PMID:21680618

  1. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

    EPA Science Inventory

    Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

  2. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    PubMed

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  3. Windscapes shape seabird instantaneous energy costs but adult behavior buffers impact on offspring

    PubMed Central

    2014-01-01

    Background Windscapes affect energy costs for flying animals, but animals can adjust their behavior to accommodate wind-induced energy costs. Theory predicts that flying animals should decrease air speed to compensate for increased tailwind speed and increase air speed to compensate for increased crosswind speed. In addition, animals are expected to vary their foraging effort in time and space to maximize energy efficiency across variable windscapes. Results We examined the influence of wind on seabird (thick-billed murre Uria lomvia and black-legged kittiwake Rissa tridactyla) foraging behavior. Airspeed and mechanical flight costs (dynamic body acceleration and wing beat frequency) increased with headwind speed during commuting flights. As predicted, birds adjusted their airspeed to compensate for crosswinds and to reduce the effect of a headwind, but they could not completely compensate for the latter. As we were able to account for the effect of sampling frequency and wind speed, we accurately estimated commuting flight speed with no wind as 16.6 ms?1 (murres) and 10.6 ms?1 (kittiwakes). High winds decreased delivery rates of schooling fish (murres), energy (murres) and food (kittiwakes) but did not impact daily energy expenditure or chick growth rates. During high winds, murres switched from feeding their offspring with schooling fish, which required substantial above-water searching, to amphipods, which required less above-water searching. Conclusions Adults buffered the adverse effect of high winds on chick growth rates by switching to other food sources during windy days or increasing food delivery rates when weather improved. PMID:26019870

  4. Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study

    PubMed Central

    Han, T S; Hart, C L; Haig, C; Logue, J; Upton, M N; Watt, G C M; Lean, M E J

    2015-01-01

    Objective Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. Design Cross-sectional general population survey. Setting Scotland. Participants 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45–64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30–59 years surveyed in 1996. Main measures Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. Results Regression coefficients for BMI associations between father–son (0.30) and mother–daughter (0.33) were greater than father–daughter (0.23) or mother–son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m2. Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. Conclusions There are

  5. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    SciTech Connect

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  6. Effects of number and gender of offspring on quality of life among older adults: evidence from the Korean Longitudinal Study of Aging, 2006–2012

    PubMed Central

    Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Cho, Kyung-Hee; Choi, Jae-Woo; Park, Eun-Cheol

    2015-01-01

    Objectives We examined correlations between number and gender of offspring and health-related quality of life (HRQoL) and quality of life (QoL) in older adults. Setting We used data from the 2006–2012 data sets of the Korean Longitudinal Study of Aging. Participants There were 10 242, 8680, 7907 and 7480 participants in 2006, 2008, 2010 and 2012, respectively. Interventions Number and gender of offspring. Primary and secondary outcome measures We measured participants’ QoL and HRQoL using a visual analogue scale developed by the Korea Labour Institute and which is similar to the EQ-VAS, a European measure. Results We estimated the HRQoL and QoL of individuals with offspring. Estimates for the HRQoL and QoL of parents with no offspring were −7.762 and −9.384, respectively (both p<0.0001) versus parents with two offspring. For parents with five or more offspring, the estimates for the HRQoL and QoL were −1.529 and 0.885, respectively (p<0.001 and p<0.017, respectively) compared with parents with two offspring. For fathers with no offspring compared with fathers with two offspring, the estimates for the HRQoL and QoL were −6.143 and −7.492, respectively (both p<0.0001). Conclusions These results suggest that number of offspring is associated with both HRQoL and QoL. Those with no offspring showed the lowest HRQoL and QoL. Although having five or more children had positive associations with QoL, it had negative associations with HRQoL. Public health services for those with poor quality of life should provide effective support programmes and services based on these findings. PMID:26063566

  7. Discrepancy in reports of support exchanges between parents and adult offspring: within- and between-family differences.

    PubMed

    Kim, Kyungmin; Zarit, Steven H; Birditt, Kira S; Fingerman, Karen L

    2014-04-01

    Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PMID:24548009

  8. An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring.

    PubMed

    Wirbisky, Sara E; Weber, Gregory J; Sepúlveda, Maria S; Lin, Tsang-Long; Jannasch, Amber S; Freeman, Jennifer L

    2016-01-01

    The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. PMID:26891955

  9. An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

    PubMed Central

    Wirbisky, Sara E.; Weber, Gregory J.; Sepúlveda, Maria S.; Lin, Tsang-Long; Jannasch, Amber S.; Freeman, Jennifer L.

    2016-01-01

    The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. PMID:26891955

  10. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring.

    PubMed

    O'Loan, Jonathan; Eyles, Darryl W; Kesby, James; Ko, Pauline; McGrath, John J; Burne, Thomas H J

    2007-04-01

    Developmental vitamin D (DVD) deficiency alters brain development and behaviour in the rat. The aim of this study was to vary levels of vitamin D deficiency during gestation and examine the effects on developmental milestones and behaviour in adult offspring. By manipulating the withdrawal and reintroduction of vitamin D in the diet of female Sprague-Dawley rats, their offspring were subjected to four different prenatal vitamin D conditions: (a) control (normal vitamin D throughout gestation); (b) early-DVD deficiency; (c) late-DVD deficiency; and (d) full-DVD deficiency. We show that the standard measure for vitamin D status, 25(OH)D(3), can be significantly manipulated within 7 days by dietary intervention. We also show that levels of the active form of this vitamin, 1,25(OH)(2)D(3), replete within the same time frame as 25(OH)D(3) but are slower to deplete. Developmental milestones remained normal across all four dietary groups. Concerning the adult behavioural phenotype, both full- and late-DVD deficiency were associated with MK-801-induced hyperlocomotion. Overall, these data suggest that vitamin D deficiency restricted to late gestation only is sufficient to disrupt adult brain functioning in the rat. These findings suggest there may be a therapeutic window for maternal dietary intervention in the DVD model of psychosis. PMID:17276604

  11. Effects of mother's dietary exposure to acesulfame-K in Pregnancy or lactation on the adult offspring's sweet preference.

    PubMed

    Zhang, Gen-Hua; Chen, Meng-Ling; Liu, Si-Si; Zhan, Yue-Hua; Quan, Ying; Qin, Yu-Mei; Deng, Shao-Ping

    2011-11-01

    This study investigates whether mother's exposure to the artificial sweetener acesulfame-K (AK) during pregnancy or lactation affected her adult offspring's sweet preference. It was found that mother's dietary exposure to AK in pregnancy or lactation decreased the preference thresholds for AK and sucrose solutions in the adult offspring, whereas the preference pattern and the most preferred concentration for AK or sucrose solution were unchanged. Furthermore, the preference scores in the exposure groups were increased significantly when compared with the control group at a range of concentrations for AK or sucrose solution. The existence of AK and its dynamic changes within 24 h in amniotic fluid during pregnancy or in mother's milk during lactation after a single oral infusion of AK solution were revealed by the methods of reversed-phase high-performance liquid chromatography and mass spectrometry. Our data suggest that AK can be ingested by the prenatal or postnatal mice through their mother's amniotic fluid or breast milk, producing a long-dated function on the adult's sweet preference. PMID:21653241

  12. Maternal Dietary Loads of Alpha-Tocopherol Increase Synapse Density and Glial Synaptic Coverage in the Hippocampus of Adult Offspring

    PubMed Central

    Salucci, S.; Ambrogini, P.; Lattanzi, D.; Betti, M.; Gobbi, P.; Galati, C.; Galli, F.; Cuppini, R.; Minelli, A.

    2014-01-01

    An increased intake of the antioxidant α-Tocopherol (vitamin E) is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Gliasynapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses) was increased. These findings indicate that gestational and neonatal exposure to supranutritional Tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant gliasynapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning. PMID:24998923

  13. Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring.

    PubMed

    Del Bas, Josep Maria; Crescenti, Anna; Arola-Arnal, Anna; Oms-Oliu, Gemma; Arola, Lluís; Caimari, Antoni

    2015-12-01

    Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring. PMID:26365577

  14. Months of asynchrony in offspring production but synchronous adult emergence: the role of diapause in an ectoparasite's life cycle.

    PubMed

    Härkönen, Laura; Kaitala, Arja

    2013-12-01

    Off-host stages of temperate zone ectoparasites must overcome two challenges: coping with unfavorable seasons and synchronizing their life cycles with host availability. In general, little is known about the seasonal cycles of insect ectoparasites of warm-blooded animals. The current study investigates the unusual phenology of a viviparous hippoboscid fly, the deer ked (Lipoptena cervi L.), that parasitizes boreal cervids. Despite months of asynchrony in offspring production, the adults emerge synchronously in mid-August across the northern boreal zone. We examined the role of diapause variation in the synchronization of life cycles by testing adult emergence success and time in relation to offspring birth month (October to April) and with respect to chilling time and photoperiod. Unexpectedly, we found that photoperiod had no role in regulating the life cycle, but diapause was maintained as long as pupae were exposed to cold. Pupae born before February needed a slightly longer exposure to high temperatures to terminate diapause if the cold period was short. Despite the apparent importance of a long period of chilling for life cycle synchrony, it was not required to terminate diapause. This finding of cold mainly preventing, rather than promoting, diapause termination is not novel among temperate insects, but it is rare. Slow diapause termination as a response to exceptionally long exposure to high, not low, temperatures seems to be a cornerstone for synchronizing the life cycle in the deer ked. PMID:24216221

  15. The reporting of maltreatment experiences during the Adult Attachment Interview in a sample of pregnant adolescents.

    PubMed

    Madigan, Sheri; Vaillancourt, Kyla; McKibbon, Amanda; Benoit, Diane

    2012-01-01

    This present student examines maltreatment experiences reported by 55 high-risk pregnant adolescents in response to a slightly adapted version of the Adult Attachment Interview (AAI; George, Kaplan, & Main, 1996 ). Previous research has suggested that the rates of unresolved states of mind regarding trauma in response to the AAI may be underestimated due to the lack of direct questions and associated probes regarding physical, sexual, and emotional abuse. We address this concern by including behaviorally phrased questions and probes regarding maltreatment experiences into the original format of the AAI and examine the concordance between reports of maltreatment experiences in response to the AAI and the Childhood Trauma Questionnaire (CTQ). Maltreatment experiences in response to the AAI were evaluated using the Maltreatment Classification Scale developed by Barnett, Manly, and Cicchetti (1993). We also examine the association between unresolved states of mind and dissociation using the Adolescent Dissociative Experience Scale. Results revealed a significant concordance between reports of maltreatment in response to the AAI and CTQ measures. Reports of maltreatment were prevalent in this sample: across the AAI and CTQ measures, 96% of pregnant adolescents reported some form of emotional abuse, 84% physical abuse, 59% sexual abuse, and 88% reported neglect. Sexual abuse history uniquely predicted unresolved status in response to the AAI. Self-reports of dissociation were significantly associated with unresolved states of mind. Results suggest that the inclusion of behaviorally focused questions and probes regarding maltreatment in the AAI protocol can further contribute to the clinical and theoretical value of this tool. PMID:22385310

  16. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

    PubMed

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  17. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    PubMed Central

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  18. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    PubMed

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. PMID:25986755

  19. Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring.

    PubMed

    Yüksel, Murat; Nazıroğlu, Mustafa; Özkaya, Mehmet Okan

    2016-05-01

    We investigated the effects of mobile phone (900 and 1800 MHz)- and Wi-Fi (2450 MHz)-induced electromagnetic radiation (EMR) exposure on uterine oxidative stress and plasma hormone levels in pregnant rats and their offspring. Thirty-two rats and their forty newborn offspring were divided into the following four groups according to the type of EMR exposure they were subjected to: the control, 900, 1800, and 2450 MHz groups. Each experimental group was exposed to EMR for 60 min/day during the pregnancy and growth periods. The pregnant rats were allowed to stand for four generations (total 52 weeks) before, plasma and uterine samples were obtained. During the 4th, 5th, and 6th weeks of the experiment, plasma and uterine samples were also obtained from the developing rats. Although uterine lipid peroxidation increased in the EMR groups, uterine glutathione peroxidase activity (4th and 5th weeks) and plasma prolactin levels (6th week) in developing rats decreased in these groups. In the maternal rats, the plasma prolactin, estrogen, and progesterone levels decreased in the EMR groups, while the plasma total oxidant status, and body temperatures increased. There were no changes in the levels of reduced glutathione, total antioxidants, or vitamins A, C, and E in the uterine and plasma samples of maternal rats. In conclusion, although EMR exposure decreased the prolactin, estrogen, and progesterone levels in the plasma of maternal rats and their offspring, EMR-induced oxidative stress in the uteri of maternal rats increased during the development of offspring. Mobile phone- and Wi-Fi-induced EMR may be one cause of increased oxidative uterine injury in growing rats and decreased hormone levels in maternal rats. TRPV1 cation channels are the possible molecular pathways responsible for changes in the hormone, oxidative stress, and body temperature levels in the uterus of maternal rats following a year-long exposure to electromagnetic radiation exposure from mobile

  20. Maternal Undernutrition Programs Offspring Adrenal Expression of Steroidogenic Enzymes

    PubMed Central

    Khorram, Naseem M.; Magee, Thomas R.; Wang, Chen; Desai, Mina; Ross, Michael; Khorram, Omid

    2011-01-01

    The aim of this study was to determine the influence of maternal undernutrition (MUN) on maternal and offspring adrenal steoridogenic enzymes. Pregnant Sprague-Dawley rats were 50% food-restricted from day 10 of gestation until delivery. Control animals received ad libitum food. Offspring were killed on day 1 of life (P1) and at 9 months. We determined the messenger RNA (mRNA) expression of steroidogneic enzymes by real-time reverse transcriptase polymerized chain reaction (RT-PCR). Maternal undernutrition inhibited maternal adrenal expression of P450 cholesterol side-chain cleavage enzyme (CYP11A1), 11 beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and adrenocorticotropic hormone (ACTH) receptor (ACTH-R; MC2 gene) compared with control offspring. There was a marked downregulation in the expression of CYP11B1, CYP11B2, 11 β-hydroxysteroid dehydrogenase type 1 and 2 (HSD1 and HSD2), CYP11A1, ACTH receptor, steroidogenic acute regulatory protein (STAR), and mineralocorticoid receptor (MCR; NR3C2 gene) mRNA in P1 MUN offspring (both genders), with no changes in glucocorticoid receptor (GCR). Quantitative immunohistochemical analysis confirmed the PCR data for GCR and MCR in P1 offspring and demonstrated lower expression of leptin receptor protein (Ob-Ra/Ob-Rb) and mRNA in P1 MUN offspring. In 9-month adult male MUN offspring, the expression of HSD1, CYP11A1, CYP11B2, Ob-Ra/Ob-Rb, and GCR mRNA were significantly upregulated with a trend toward an increase in ACTH-R and a decrease in 17 alpha-hydroxylase (CYP17A1) expression. In adult female MUN offspring, similar to males, the expression of CYP11A1, ACTH-R, and Ob-Rb mRNA were increased, whereas GCR and CYP17A1 mRNA were decreased. These results indicate that the adrenal gland is a target of nutritional programming. In utero undernutrition has a global suppressive effect on maternal and P1 offspring adrenal steroidogenic enzymes in association with reduced circulating corticosterone levels in P1 offspring

  1. Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring.

    PubMed

    Sasaki, Aya; Constantinof, Andrea; Pan, Pauline; Kupferschmidt, Dave A; McGowan, Patrick O; Erb, Suzanne

    2014-05-15

    There is evidence that maternal experience prior to pregnancy can play an important role in behavioral, physiological, and genetic programming of offspring. Likewise, exposure to cocaine in utero can result in marked changes in central nervous system function of offspring. In this study, we examined whether exposure of rat dams to cocaine prior to pregnancy subsequently alters indices of behavior, physiology, and gene expression in offspring. Multiple outcome measures were examined in adult male offspring: (1) behavioral expression of cocaine-induced psychomotor activation; (2) levels of corticosterone in response to immobilization stress; and (3) expression of multiple genes, including dopamine receptor D1 (DRD1) and D2 (DRD2), glucocorticoid receptor (GR), and corticotropin-releasing factor (CRF), in functionally relevant brain regions. Adult Sprague-Dawley females were exposed to cocaine (15-30 mg/kg, i.p.) or saline for 10 days, and were then mated to drug naïve males of the same strain. Separate groups of adult male offspring were tested for their acute psychomotor response to cocaine (0, 15, 30 mg/kg, i.p.), corticosterone responsivity to 20 min of immobilization stress, and expression of multiple genes using quantitative PCR. Offspring of dams exposed to cocaine prior to conception exhibited increased psychomotor sensitivity to cocaine, and upregulated gene expression of DRD1 in the medial prefrontal cortex (mPFC). Neither stress-induced corticosterone levels nor gene expression of GR or CRF genes were altered. These data suggest that cocaine exposure before pregnancy can serve to enhance psychomotor sensitivity to cocaine in offspring, possibly via alterations in dopamine function that include upregulation of the DRD1. PMID:24583058

  2. Different effects of prenatal stress on ERK2/CREB/Bcl-2 expression in the hippocampus and the prefrontal cortex of adult offspring rats.

    PubMed

    Zhu, Zeen; Sun, Hongli; Gong, Xiaojie; Li, Hui

    2016-05-25

    It has become increasingly evident that prenatal stress and its psychological and physiological concomitants are associated with the pathophysiology of mood disorders. However, the mechanisms underlying the prenatal stress-induced offspring's anxiety disorders remain unknown. We recently reported that prenatal stress enhanced anxiety-like behavior in adult offspring rat, and involved N-methyl-D-aspartate receptor subunits, including NR1 and NR2A. In the present research, using the same prenatal stress model, we measured the ERK2/CREB/Bcl-2 mRNA levels by real-time PCR. Our findings indicated that prenatal stress decreased ERK2 and CREB mRNA levels in the hippocampus and the prefrontal cortex and Bcl-2 mRNA levels in the hippocampus of offspring rat. The results showed that the abnormal ERK2, CREB, and Bcl-2 mRNA levels may be involved in the anxiety-like behavior of adult rats with prenatal stress. PMID:27096215

  3. Maternal dietary restriction alters offspring's sleep homeostasis.

    PubMed

    Shimizu, Noriyuki; Chikahisa, Sachiko; Nishi, Yuina; Harada, Saki; Iwaki, Yohei; Fujihara, Hiroaki; Kitaoka, Kazuyoshi; Shiuchi, Tetsuya; Séi, Hiroyoshi

    2013-01-01

    Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD) or 50% dietary restriction (DR) groups from gestation day 12 to parturition. After parturition, dams were fed AD chow. After weaning, the pups were also fed AD into adulthood. At adulthood (aged 8-9 weeks), we carried out sleep recordings. Although offspring mice displayed a significantly reduced body weight at birth, their weights recovered three days after birth. Enhancement of electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (NREM) sleep was observed in the DR mice over a 24-hour period without changing the diurnal pattern or amounts of wake, NREM, or rapid eye movement (REM) sleep. In addition, DR mice also displayed an enhancement of EEG-SWA rebound after a 6-hour sleep deprivation and a higher threshold for waking in the face of external stimuli. DR adult offspring mice exhibited small but significant increases in the expression of hypothalamic peroxisome proliferator-activated receptor α (Pparα) and brain-specific carnitine palmitoyltransferase 1 (Cpt1c) mRNA, two genes involved in lipid metabolism. Undernutrition during pregnancy may influence sleep homeostasis, with offspring exhibiting greater sleep pressure. PMID:23741310

  4. Transmission of cultural values among Mexican-origin parents and their adolescent and emerging adult offspring.

    PubMed

    Perez-Brena, Norma J; Updegraff, Kimberly A; Umaña-Taylor, Adriana J

    2015-06-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths' adjustment and family dynamics. The current study examined the reciprocal associations in parents' and two offspring's cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers' values were associated with increases in youths' values 5 years later. In contrast, youths' familism values were associated with increases in fathers' familism values 5 years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support is crucial. PMID:25470657

  5. Maternal exposure to diets containing high fructose and saturated fats, low B vitamins, or their combination programs growth, adiposity, and insulin sensitivity in adult offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early exposure to unfavorable nutrition programs increases risk of adult-onset diseases. In this rat study, we investigate morphological, metabolic and endocrinal phenotypes of offspring born to dams consuming isocaloric diets containing 30% fructose, 9.9% coconut fat and 0.5% cholesterol (F+SFA), m...

  6. Perinatal citalopram does not prevent the effect of prenatal stress on anxiety, depressive-like behaviour and serotonergic transmission in adult rat offspring.

    PubMed

    Zohar, Inbar; Shoham, Shai; Weinstock, Marta

    2016-02-01

    It is still not clear whether the selective serotonin reuptake inhibitors frequently prescribed to depressed pregnant women improve the behavioural outcome in their children. The current study investigated whether administration of citalopram to pregnant rats could prevent anxiety and depressive-like behaviour induced by gestational stress in their offspring, and restore the expression of serotonin 1A autoreceptors in GABAergic interneurons in the medial prefrontal cortex and dorsal raphe nuclei in males, and of corticotropin-releasing factor type 2 receptors in GABAergic interneurons in the dorsal raphe nuclei in females. Activation of these receptors modulates serotonergic transmission to target areas and is reduced in a sex-dependent manner by prenatal stress. Citalopram (10 mg/kg/day), administered orally from day 7 of gestation until 21 days postpartum, prevented the increase in anxiety in stressed mothers but did not reduce anxiety and depressive-like behaviour in their offspring and even induced depressive-like behaviour in the offspring of control mothers. Citalopram failed to restore the reduction in the expression of serotonin 1A autoreceptors in the prefrontal cortex of males and in corticotropin-releasing factor type 2 receptors in the dorsal raphe nuclei of females induced by prenatal stress. Prenatal citalopram did not prevent the behavioural changes or reduction in serotonergic transmission to target areas induced by prenatal stress. It had adverse behavioural effects in the offspring of control rats, which, together with the lack of any change in prenatally-stressed rats, may be due to inhibition of the foetal serotonin transporter thereby preventing normal development of the serotonin system. PMID:26669896

  7. Excess maternal salt or fructose intake programmes sex-specific, stress- and fructose-sensitive hypertension in the offspring.

    PubMed

    Gray, Clint; Gardiner, Sheila M; Elmes, Matthew; Gardner, David S

    2016-02-28

    The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (± 4% salt) and water (± 10% fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypotensive (10 mmHg MAP) above and below controls, respectively. Sex differences were unrelated to endothelial nitric oxide activity in vivo, but isolation-induced anxiety revealed a significantly steeper coupling between blood pressure and heart rate in salt-exposed male offspring but not in female offspring. MAP of all offspring was refractory to salt loading but sensitive to subsequent dietary fructose, an effect exacerbated in female offspring from fructose-fed dams. Circadian analyses of pressure in all offspring revealed higher mean set-point for heart rate and relative non-dipping of nocturnal pressure. In conclusion, increased salt and fructose in the maternal diet has lasting effects on offspring cardiovascular function that is sex-dependent and related to the offspring's stress-response axis. PMID:26653028

  8. Evaluation of possible toxic effects of spearmint (Mentha spicata) on the reproductive system, fertility and number of offspring in adult male rats

    PubMed Central

    Nozhat, Fatemeh; Alaee, Sanaz; Behzadi, Khodabakhsh; Azadi Chegini, Najmeh

    2014-01-01

    Objective: In this study we investigated the effects of spearmint (Mentha spicata Labiatae) on the reproductive system, fertility and number of offspring in adult male rats. Materials and Methods: Adult Wistar male rats in one control (C) and three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively. Following this treatment, the animals’ weights, and the standard weight of reproductive tissues, sperm count, sperm motility and serum testosterone concentration were measured, and reproductive tissues were examined histopathologically. To evaluate the effects of spearmint on fertility of male rats and growth of their offspring, male rats of the control and experimental groups mated with untreated female rats. Results: Results showed that spearmint did not affect the rats’ body and reproductive tissue weights. The sperm count, fast and slow progressive motility of sperm and serum testosterone concentration decreased while number of non-progressive sperm and immotile sperm increased in the experimental groups compared to the control group, but none of these changes were statistically significant. Histopathological studies showed no severe changes in reproductive tissues between control and experimental groups. Number and growth of offspring born from mating of male rats with untreated female rats showed no difference. Conclusion: We concluded that spearmint has no significant toxic effect on the reproductive system, fertility and number of offspring in adult male rats at the above mentioned dose levels. However high levels of this extract may have adverse effects on male fertility. PMID:25386406

  9. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome

    PubMed Central

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-01-01

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. Key points Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet-induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational

  10. A possible association between acute infectious diarrhoea in pregnant women and congenital abnormalities in their offspring--a population-based case-control study.

    PubMed

    Acs, Nándor; Bánhidy, Ferenc; Puhó, Erzsébet H; Czeizel, Andrew E

    2010-05-01

    The possible association between Salmonella gastroenteritis (SGE) and infectious diarrhoea in pregnancy (IDP) and structural birth defects, i.e. congenital abnormalities (CA) in the offspring, has not been studied. The dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 was evaluated. There were 15 (0.07%) and 82 (0.36%) out of 22,843 cases and 23 (0.06%) and 70 (0.18%) out of 38,151 (0.34%) controls with mothers who had medically recorded SGE and IDP, respectively. There was no association of SGE and a higher risk of CA. However, a higher risk of cleft lip +/- palate, congenital limb deficiencies, multiple CAs and cardiovascular CAs was found in the offspring of mothers with IDP. A possible explanation for the association of IDP with higher risk for some specific CAs may be the high fever in IDP. PMID:20100117

  11. Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway.

    PubMed

    Forrest, C M; Khalil, O S; Pisar, M; McNair, K; Kornisiuk, E; Snitcofsky, M; Gonzalez, N; Jerusalinsky, D; Darlington, L G; Stone, T W

    2013-12-19

    During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog. PMID:24076085

  12. Young Adult Exposure to Cardiovascular Risk Factors and Risk of Events Later in Life: The Framingham Offspring Study

    PubMed Central

    Pletcher, Mark J.; Vittinghoff, Eric; Thanataveerat, Anusorn; Bibbins-Domingo, Kirsten

    2016-01-01

    Background It is unclear whether coronary heart disease (CHD) risk factor exposure during early adulthood contributes to CHD risk later in life. Our objective was to analyze whether extent of early adult exposures to systolic and diastolic blood pressure (SBP, DBP) and low-and high-density lipoprotein cholesterol (LDL, HDL) are independent predictors of CHD events later in life. Methods and Findings We used all available measurements of SBP, DBP, LDL, and HDL collected over 40 years in the Framingham Offspring Study to estimate risk factor trajectories, starting at age 20 years, for all participants. Average early adult (age 20–39) exposure to each risk factor was then estimated, and used to predict CHD events (myocardial infarction or CHD death) after age 40, with adjustment for risk factor exposures later in life (age 40+). 4860 participants contributed an average of 6.3 risk factor measurements from in-person examinations and 24.5 years of follow-up after age 40, and 510 had a first CHD event. Early adult exposures to high SBP, DBP, LDL or low HDL were associated with 8- to 30-fold increases in later life CHD event rates, but were also strongly correlated with risk factor levels later in life. After adjustment for later life levels and other risk factors, early adult DBP and LDL remained strongly associated with later life risk. Compared with DBP≤70 mmHg, adjusted hazard ratios (HRs) were 2.1 (95% confidence interval: 0.8–5.7) for DBP = 71–80, 2.6 (0.9–7.2) for DBP = 81–90, and 3.6 (1.2–11) for DBP>90 (p-trend = 0.019). Compared with LDL≤100 mg/dl, adjusted HRs were 1.5 (0.9–2.6) for LDL = 101–130, 2.2 (1.2–4.0) for LDL = 131–160, and 2.4 (1.2–4.7) for LDL>160 (p-trend = 0.009). While current levels of SBP and HDL were also associated with CHD events, we did not detect an independent association with early adult exposure to either of these risk factors. Conclusions Using a mixed modeling approach to estimation of young adult exposures

  13. Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge

    PubMed Central

    Long, Nathan M.; Rule, Daniel C.; Tuersunjiang, Nuermaimaiti; Nathanielsz, Peter W.; Ford, Stephen P.

    2015-01-01

    Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an ad libitum feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term. All ewes were fed to requirements during lactation. After weaning, F1 male offspring were fed only to maintenance requirements until adulthood (control = 7, obese = 6), when they were fed ad libitum for 12 weeks with intake monitored. At the end of the feeding challenge offspring were given an intravenous glucose tolerance test (IVGTT), necropsied, and adipose tissue collected. During the feeding trial F1obese males consumed more (P < 0.01), gained more weight (P < 0.01) and became heavier (P < 0.05) than F1control males. During IVGTT, Obese F1 offspring were hyperglycemic and hypoinsulinemic (P < 0.01) compared to F1 control F1. At necropsy perirenal and omental adipose depots weights were 47% and 58% greater respectively and subcutaneous fat thickness 41% greater in F1obese vs F1control males (P < 0.05). Adipocyte diameters were greater (P ≤ 0.04) in perirenal, omental and subcutaneous adipose depots in F1obese males (11, 8 and 7% increase vs. control, respectively). When adipose tissue was incubated for 2 hrs with C-14 labeled acetate, subcutaneous, perirenal, and omental adipose tissue of F1 obese males exhibited greater incorporation (290, 83, and 90% increase vs. control, respectively P < 0.05) of acetate into lipids. Expression of fatty acid transporting, binding, and syntheses mRNA and protein was increased (P < 0.05) compared to F1 control offspring. Maternal obesity increased appetite and adiposity associated with increased adipocyte diameters and increased fatty acid synthesis in over-nourished adult male offspring. PMID:25875659

  14. Transmission of Cultural Values among Mexican American Parents and their Adolescent and Emerging Adult Offspring

    PubMed Central

    Perez-Brena, Norma J.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.

    2015-01-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths’ adjustment and family dynamics. The current study examined the reciprocal associations in parents’ and two offspring’s cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers’ values were associated with increases in youths’ values five years later. In contrast, youths’ familism values were associated with increases in fathers’ familism values five years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant-status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support are crucial. PMID:25470657

  15. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    PubMed Central

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

    Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

  16. Protective role of taurine in developing offspring affected by maternal alcohol consumption

    PubMed Central

    Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

    2015-01-01

    Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

  17. Chronic PFOS exposures induce life stage-specific behavioral deficits in adult zebrafish and produce malformations in F1 offspring

    PubMed Central

    Chen, Jiangfei; Huang, Changjiang; Das, Siba R.; La Du, Jane; Corvi, Margaret M.; Bai, Chenglian; Chen, Yuanhong; Tanguay, Robert L.; Dong, Qiaoxiang

    2014-01-01

    Perfluorooctanesulphonicacid (PFOS) is an organic contaminant that is ubiquitous in the environment, wildlife, and humans. Few studies have assessed the effects of chronic PFOS exposure on central nervous system function in aquatic organisms. The present study defined the behavioral effects of varying life span chronic exposures to low dose PFOS in zebrafish. The zebrafish were treated with vehicle control or 0.5μM PFOS during 1–21, 21–120, or 1–120 day post fertilization (dpf). Chronic PFOS exposure impaired the adult zebrafish behavior mode under the tapping stimulus. The movement speed of 1–120 dpf exposed fish was significantly increased compared with control, while 1–21 and 21–120 dpf exposed groups were not severely affected. PFOS residues in F1 embryos derived from parental exposure during both the 1–120 and 21–120 dpf groups was significantly higher than control, and F1 embryos in these two groups showed obvious malformations, such as uninflated swim bladder (USB) and bent spine (BS). Larvae of the parental exposed to PFOS from 1–21 or 21–120 dpf elicited a higher swim rate than control in both the light and dark periods. Embryos derived from the 1–120 dpf group showed a statistically lower speed in the light period and a higher speed in the dark period as compared with control. Though there is little PFOS residue in 1–21 dpf group, the adverse behavioral effects on both adult and F1 larvae indicate that exposure during the first 21 dpf induce long-term neurobehavior toxicity. Our findings demonstrate that chronic exposure to low dose PFOS in different life stage adversely impacts adult behavior, subsequent offspring malformation, and larval behavior. PMID:23059794

  18. Risk Factors Associated with Aortic and Carotid Intimal-Medial Thickness in Adolescents and Young Adults: the Muscatine Offspring Study

    PubMed Central

    Dawson, Jeffrey D.; Sonka, Milan; Blecha, Mary Beth; Lin, Wenjiao; Davis, Patricia H.

    2009-01-01

    Objectives To determine whether cardiovascular risk factors are associated with aortic and carotid intimal-medial thickness (aIMT and cIMT) in adolescents and young adults. Background Atherosclerotic lesions begin developing in youth, first in the distal abdominal aorta and later in the carotid arteries. Knowledge of how risk factors relate to aIMT and cIMT may help in the design of early interventions to prevent cardiovascular disease. Methods Participants were 635 members of the Muscatine Offspring cohort. The mean aIMT and cIMT were measured using an automated reading program. Results The means (SDs) of aIMT and cIMT were 0.63 (0.14) mm and 0.49 (0.04) mm, respectively. In adolescents (ages 11 to 17), aIMT was associated with triglycerides, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist/hip ratio, after adjusting for age, gender, and height. In young adults (ages 18 to 34), aIMT was associated with those same five risk factors, plus HDL-cholesterol and pulse pressure. In adolescents, cIMT was associated with SBP, pulse pressure, heart rate, BMI, and waist/hip ratio. In young adults, cIMT was associated total cholesterol, LDL-cholesterol, triglycerides, SBP, .DBP, BMI, waist/hip ratio, and HbA1C. In both age groups, aIMT and cIMT were significantly correlated with the PDAY coronary artery risk score. Conclusions Both aIMT and cIMT are associated with cardiovascular risk factors. Using aIMT in adolescents gives information beyond that obtained from cIMT alone. Measurement of aIMT and cIMT may help identify those at risk for premature cardiovascular disease. PMID:19520251

  19. Adult glucocorticoid exposure leads to transcriptional and DNA methylation changes in nuclear steroid receptors in the hippocampus and kidney of mouse male offspring.

    PubMed

    Petropoulos, Sophie; Matthews, Stephen G; Szyf, Moshe

    2014-02-01

    Synthetic glucocorticoids (sGCs) are commonly prescribed for the management of inflammatory and endocrine disorders. However, nothing is known regarding the effects of sGC on adult germline methylome and whether these effects can be transmitted to the next generation. We hypothesized that administration of sGC to adult male mice alters DNA methylation in mature sperm and modifies the transcription and methylation of steroid receptors in male F1 offspring. Adult C57BL/6 males (n = 10/group) were injected on five consecutive days with 1 mg/kg sGC (i.e., dexamethasone) or vehicle and euthanized 35 or 60 days after initial treatment or bred with control females (60 days postinitial treatment; n = 5/group). A significant increase in global non-CpG methylation was observed in F0 sperm 60 days following sGC treatment. In the hippocampus and kidney of Postnatal Day 50 (PND50) and PND240 male offspring derived from fathers exposed to sGC, significant differences in mineralocorticoid receptor (Nr3c2; Mr), estrogen alpha receptor (Nr3a1; Ers1), and glucocorticoid receptor (Nr3c1; Gr) expression were observed. Furthermore, significant demethylation in regulatory regions of Mr, Gr, and Esr1 was observed in the PND50 kidney derived from fathers exposed to sGC. This is the first demonstration that paternal pharmacological exposure to sGC can alter the expression and DNA methylation of nuclear steroid receptors in brain and somatic tissues of offspring. These findings provide proof of principle that adult male exposure to sGC can affect DNA methylation and gene expression in offspring, indicating the possibility that adult experiences that evoke increases in endogenous glucocorticoid (i.e., stress) might have similar effects. PMID:24451982

  20. Effects of Family Dysfunction and Parental Problem Drinking on Adult Offspring.

    ERIC Educational Resources Information Center

    Soukup, Dorothy Therese

    Few empirical studies have been conducted to determine the characteristics and functioning of Adult Children of Alcoholics (ACoAs). This study examined the emotional and behavioral wellness of college students (N=253) raised in a variety of family environments with varying levels of healthy/unhealthy functioning. For the purposes of this study…

  1. Breastfeeding Intentions Among Pregnant Adolescents and Young Adults and Their Partners

    PubMed Central

    Divney, Anna A.; Magriples, Urania; Hansen, Nathan; Gordon, Derrick; Kershaw, Trace

    2013-01-01

    Abstract Background Rates of breastfeeding remain disproportionately low among young mothers in the United States. Although breastfeeding behavior may be most directly related to breastfeeding intention, little is known about breastfeeding intentions among young women who are expecting a baby. Subjects and Methods Pregnant adolescents and young adults (14–21 years old) and their male partners were recruited for participation. Females were asked if they intended to breastfeed, and their partners were asked if they wanted their partners to breastfeed; participants indicated reasons for their responses. Logistic regression modeling was used to determine the associations between breastfeeding intentions and sociodemographic characteristics, relationship characteristics, and partner's intention to breastfeed. Results Approximately 73% of females reported intending to breastfeed, and 80% of males reported wanting his partner to breastfeed, most commonly because it is “healthier for the baby” and “a more natural way to feed the baby.” Sociodemographic and relationship characteristics explained a small amount of variance of breastfeeding intention (15% and 4% among females, respectively, and 8% and 4% among males, respectively). Partner intention explained an additional 23% and 24% of the variance in individual intention for females and males, respectively. Females who had experienced intimate partner violence (IPV) from their current partner had lower odds of intending to breastfeed (odds ratio=0.37; 95% confidence interval=0.16, 0.84). Race/ethnicity modified associations among both genders. Conclusions These findings emphasize the importance of dyadic approaches and suggest strategies for improving breastfeeding intentions and behavior among young couples expecting a baby. These results are also among the first to document the relationship between IPV and breastfeeding intentions among young women. PMID:23611330

  2. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring.

    PubMed

    Cyrus, Chu C Y; Lee, Ronald D

    2013-09-01

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages. PMID:23648187

  3. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring

    PubMed Central

    Cyrus Chu, C.Y.; Lee, Ronald D.

    2013-01-01

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages. PMID:23648187

  4. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development. PMID:26632603

  5. Too risky to settle: avian community structure changes in response to perceived predation risk on adults and offspring

    USGS Publications Warehouse

    Hua, Fangyuan; Fletcher, Robert J.; Sieving, Kathryn E.; Dorazio, Robert M.

    2013-01-01

    Predation risk is widely hypothesized as an important force structuring communities, but this potential force is rarely tested experimentally, particularly in terrestrial vertebrate communities. How animals respond to predation risk is generally considered predictable from species life-history and natural-history traits, but rigorous tests of these predictions remain scarce. We report on a large-scale playback experiment with a forest bird community that addresses two questions: (i) does perceived predation risk shape the richness and composition of a breeding bird community? And (ii) can species life-history and natural-history traits predict prey community responses to different types of predation risk? On 9 ha plots, we manipulated cues of three avian predators that preferentially prey on either adult birds or offspring, or both, throughout the breeding season. We found that increased perception of predation risk led to generally negative responses in the abundance, occurrence and/or detection probability of most prey species, which in turn reduced the species richness and shifted the composition of the breeding bird community. Species-level responses were largely predicted from the key natural-history trait of body size, but we did not find support for the life-history theory prediction of the relationship between species' slow/fast life-history strategy and their response to predation risk.

  6. Ovarian dysfunctions in adult female rat offspring born to mothers perinatally exposed to low doses of bisphenol A.

    PubMed

    Santamaría, Clarisa; Durando, Milena; Muñoz de Toro, Mónica; Luque, Enrique H; Rodriguez, Horacio A

    2016-04-01

    The study of oral exposure to the environmental estrogen bisphenol A (BPA) during the perinatal period and its effects on ovarian functionality in adulthood has generated special interest. Thus, our objective was to investigate ovarian folliculogenesis and steroidogenesis in adult female rat offspring born to mothers exposed to low doses of BPA (BPA50: 50μg/kgday; BPA0.5: 0.5μg/kgday) by the oral route during gestation and breastfeeding. Ovaries from both BPA-treated groups showed reduced primordial follicle recruitment and a greater number of corpora lutea, indicating an increased number of ovulated oocytes, coupled with higher levels of mRNA expression of 3β-hydroxysteroid dehydrogenase and serum progesterone. BPA50-treated animals had lower expression of androgen receptor (AR) at different stages of the growing follicle population. BPA0.5-treated rats evidenced an imbalance of AR expression between primordial/primary follicles, with higher mRNA-follicle-stimulating hormone receptor expression. These results add to the growing evidence that folliculogenesis and steroidogenesis are targets of BPA within the ovary. PMID:26658420

  7. Prenatal Stress Enhances Excitatory Synaptic Transmission and Impairs Long-Term Potentiation in the Frontal Cortex of Adult Offspring Rats

    PubMed Central

    Sowa, Joanna; Bobula, Bartosz; Glombik, Katarzyna; Slusarczyk, Joanna; Basta-Kaim, Agnieszka; Hess, Grzegorz

    2015-01-01

    The effects of prenatal stress procedure were investigated in 3 months old male rats. Prenatally stressed rats showed depressive-like behavior in the forced swim test, including increased immobility, decreased mobility and decreased climbing. In ex vivo frontal cortex slices originating from prenatally stressed animals, the amplitude of extracellular field potentials (FPs) recorded in cortical layer II/III was larger, and the mean amplitude ratio of pharmacologically-isolated NMDA to the AMPA/kainate component of the field potential—smaller than in control preparations. Prenatal stress also resulted in a reduced magnitude of long-term potentiation (LTP). These effects were accompanied by an increase in the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These data demonstrate that stress during pregnancy may lead not only to behavioral disturbances, but also impairs the glutamatergic transmission and long-term synaptic plasticity in the frontal cortex of the adult offspring. PMID:25749097

  8. Timing of Maternal Immunization Affects Immunological and Behavioral Outcomes of Adult Offspring in Siberian Hamsters (Phodopus sungorus).

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2016-07-01

    Maternal influences are an important contributing factor to offspring survival, development, and behavior. Common environmental pathogens can induce maternal immune responses and affect subsequent development of offspring. There are likely sensitive periods during pregnancy when animals are particularly vulnerable to environmental disruption. Here we characterize the effects of maternal immunization across pregnancy and postpartum on offspring physiology and behavior in Siberian hamsters (Phodopus sungorus). Hamsters were injected with the antigen keyhole limpet hemocyanin (KLH) (1) prior to pairing with a male (premating), (2) at separation (postmating), (3) at midpregnancy, or (4) after birth (lactation). Maternal food intake, body mass, and immunity were monitored throughout gestation, and litters were measured weekly for growth until adulthood when social behavior, hormone concentrations, and immune responses were determined. We found that immunizations altered maternal immunity throughout pregnancy and lactation. The effects of maternal treatment differed between male and female offspring. Aggressive behavior was enhanced in offspring of both sexes born to mothers treated postmating and thus early in pregnancy relative to other stages. In contrast, maternal treatment and maternal stage differentially affected innate immunity in males and females. Offspring cortisol, however, was unaffected by maternal treatment. Collectively, these data demonstrate that maternal immunization affects offspring physiology and behavior in a time-dependent and sex-specific manner. More broadly, these findings contribute to our understanding of the effects of maternal immune activation, whether it be from environmental exposure or immunization, on immunological and behavioral responses of offspring. PMID:27320639

  9. The Association of Maternal Socialization in Childhood and Adolescence with Adult Offsprings' Sympathy/Caring

    ERIC Educational Resources Information Center

    Eisenberg, Nancy; VanSchyndel, Sarah K.; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood…

  10. Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

    PubMed

    Tsoulis, Michael W; Chang, Pauline E; Moore, Caroline J; Chan, Kaitlyn A; Gohir, Wajiha; Petrik, James J; Vickers, Mark H; Connor, Kristin L; Sloboda, Deborah M

    2016-04-01

    Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood. PMID:26962114

  11. Childhood Risk Factors for Young Adult Substance Dependence Outcome in Offspring from Multiplex Alcohol Dependence Families: A Prospective Study

    PubMed Central

    Hill, Shirley Y.; Steinhauer, Stuart R.; Locke-Wellman, Jeannette; Ulrich, Richard

    2012-01-01

    Background Age of onset to begin drinking is a known risk factor for alcohol dependence. Factors have been identified that contribute to age of onset to begin regular drinking. These include reduced P300, increased postural sway, and personality variation. A longitudinal study spanning childhood to young adulthood provided the opportunity to determine if these same factors would predict the presence and onset of substance use disorders (SUD). Methods Multiplex families were identified through two or more alcohol-dependent brothers. Offspring from these multiplex or control families (n = 133) were followed annually during childhood. Using childhood predictors previously identified as risk factors for age of onset to begin drinking, SUD outcome by young adulthood was modeled. Results Familial risk status was a significant predictor of young adult SUD outcome as a main effect and as an interaction with P300 amplitude recorded before the age of 13. In adolescence (age 15), increased postural sway and familial risk predicted the SUD outcome by age 22. Analysis comparing the presence of one or both risk factors showed that those above the median for sway and below the median for P300 amplitude had substantially increased odds of developing SUD (odds ratio = 8.08 [confidence interval = 1.52– 42.83]). Conclusions Our findings indicate that among the factors predicting age of onset to begin regular drinking, P300 predicts SUD outcome across an 11-year span. The present findings provide the longest follow-up to date demonstrating that neurobiological factors in childhood are among the most salient predictors of young adult SUD outcome. PMID:19640504

  12. Self-Reported Hearing Difficulties Among Adults With Normal Audiograms: The Beaver Dam Offspring Study

    PubMed Central

    Tremblay, Kelly L.; Pinto, Alex; Fischer, Mary E.; Klein, Barbara E. K.; Klein, Ronald; Levy, Sarah; Tweed, Ted S.; Cruickshanks, Karen J.

    2016-01-01

    Objective Clinicians encounter patients who report experiencing hearing difficulty (HD) even when audiometric thresholds fall within normal limits. When there is no evidence of audiometric hearing loss, it generates debate over possible biomedical and psychosocial etiologies. It is possible that self-reported HDs relate to variables within and/or outside the scope of audiology. The purpose of this study is to identify how often, on a population basis, people with normal audiometric thresholds self-report HD and to identify factors associated with such HDs. Design This was a cross-sectional investigation of participants in the Beaver Dam Offspring Study. HD was defined as a self-reported HD on a four-item scale despite having pure-tone audiometric thresholds within normal limits (<20 dB HL0.5, 1, 2, 3, 4, 6, 8 kHz bilaterally, at each frequency). Distortion product otoacoustic emissions and word-recognition performance in quiet and with competing messages were also analyzed. In addition to hearing assessments, relevant factors such as sociodemographic and lifestyle factors, environmental exposures, medical history, health-related quality of life, and symptoms of neurological disorders were also examined as possible risk factors. The Center for Epidemiological Studies-Depression was used to probe symptoms associated with depression, and the Medical Outcomes Study Short-Form 36 mental score was used to quantify psychological stress and social and role disability due to emotional problems. The Visual Function Questionnaire-25 and contrast sensitivity test were used to query vision difficulties. Results Of the 2783 participants, 686 participants had normal audiometric thresholds. An additional grouping variable was created based on the available scores of HD (four self-report questions), which reduced the total dataset to n = 682 (age range, 21–67 years). The percentage of individuals with normal audiometric thresholds who self-reported HD was 12.0% (82 of 682). The

  13. Alteration of mitochondrial function in adult rat offspring of malnourished dams

    PubMed Central

    Reusens, Brigitte; Theys, Nicolas; Remacle, Claude

    2011-01-01

    Under-nutrition as well as over-nutrition during pregnancy has been associated with the development of adult diseases such as diabetes and obesity. Both epigenetic modifications and programming of the mitochondrial function have been recently proposed to explain how altered intrauterine metabolic environment may produce such a phenotype. This review aims to report data reported in several animal models of fetal malnutrition due to maternal low protein or low calorie diet, high fat diet as well as reduction in placental blood flow. We focus our overview on the β cell. We highlight that, notwithstanding early nutritional events, mitochondrial dysfunctions resulting from different alteration by diet or gender are programmed. This may explain the higher propensity to develop obesity and diabetes in later life. PMID:21954419

  14. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation

    PubMed Central

    Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

    2015-01-01

    Background Fetal exposure to hyperglycemia impacts negatively kidney development and function. Objective Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Design Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Results Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)—a key enzyme involved in gene expression during early development–was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Conclusion Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function. PMID:26258530

  15. Gestational and Lactational Exposure to Atrazine via the Drinking Water Causes Specific Behavioral Deficits and Selectively Alters Monoaminergic Systems in C57BL/6 Mouse Dams, Juvenile and Adult Offspring

    PubMed Central

    Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M.

    2014-01-01

    Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams’ cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams. PMID:24913803

  16. Appraisals of discriminatory events among adult offspring of Indian residential school survivors: the influences of identity centrality and past perceptions of discrimination.

    PubMed

    Bombay, Amy; Matheson, Kimberly; Anisman, Hymie

    2014-01-01

    As part of a government policy of assimilation beginning in the mid-1800s, a large proportion of Aboriginal children in Canada were forcibly removed from their homes to attend Indian Residential Schools (IRSs), a practice which continued into the 1990s. This traumatic experience had lasting negative effects not only on those who attended but also on their offspring, who were previously found to report higher levels of perceived discrimination and depressive symptoms compared with Aboriginal adults whose families were not directly affected by IRSs. In attempt to elucidate the processes involved in these previous findings, the current study (N = 399) revealed that greater levels of past perceptions of discrimination among IRS offspring, together with their greater likelihood of considering their Aboriginal heritage to be a central component of their self-concept (i.e., high identity centrality), were associated with an increased likelihood of appraising subsequent negative intergroup scenarios to be a result of discrimination and as threatening to their well-being. In turn, these altered appraisals of threat in response to the scenarios were associated with higher levels of depressive symptoms relative to non-IRS adults. The apparent reinforcing relationships between past discrimination, identity centrality, and appraisals of discrimination and threat in intergroup interactions highlight the need for interventions targeting this cycle that appears to contribute to heightened psychological distress among offspring of those who were directly victimized by collective race-based traumas. PMID:23834257

  17. Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring.

    PubMed

    Church, M W; Jen, K-L C; Anumba, J I; Jackson, D A; Adams, B R; Hotra, J W

    2010-01-01

    Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation is beneficial to fetal and infant development and might reduce the incidence and severity of preterm births by prolonging pregnancy. Consequently, supplementing maternal diets with large amounts of omega-3 FA is gaining acceptance. However, both over- and under-supplementation with omega-3 FA can harm offspring development. Adverse fetal and neonatal conditions in general can enhance age-related neural degeneration, shorten life span and cause other adult-onset disorders. We hypothesized that maternal over- and under-nutrition with omega-3 FA would shorten the offspring's life span and enhance neural degeneration in old adulthood. To test these hypotheses, female Wistar rats were randomly assigned to one of the three diet conditions starting from day 1 of pregnancy through the entire period of pregnancy and lactation. The three diets were Control omega-3 FA (omega-3/omega-6 ratio approximately 0.14), Excess omega-3 FA (omega-3/omega-6 ratio approximately 14.5) and Deficient omega-3 FA (omega-3/omega-6 ratio approximately 0% ratio). When possible, one male and female offspring from each litter were assessed for life span and sensory/neural degeneration (n=15 litters/group). The Excess offspring had shorter life spans compared to their Control and Deficient cohorts (mean+/-SEM=506+/-24, 601+/-14 and 585+/-21 days, poffspring had a higher incidence of presbycusis than the Control and Deficient groups (33.3, 4.3 and 4.5%, p=0.011) and a persistence of other sensory/neurological abnormalities and lower body weights in old adulthood. In conclusion, omega-3 FA over-nutrition or imbalance during pregnancy and lactation had adverse effects on life span and sensory/neurological function in old adulthood. The adverse outcomes in the Excess offspring were likely due to a "nutritional toxicity" during fetal and/or neonatal development

  18. Abnormal neurological responses in young adult offspring caused by excess omega-3 fatty acid (fish oil) consumption by the mother during pregnancy and lactation.

    PubMed

    Church, M W; Jen, K-L C; Jackson, D A; Adams, B R; Hotra, J W

    2009-01-01

    Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation benefits fetal and infant brain development and might reduce the severity of preterm births by prolonging pregnancy. However, diets that are relatively rich in omega-3 FA can adversely affect fetal and infant development and the auditory brainstem response (ABR), a measure of brain development and sensory function. We previously examined the offspring of female rats fed excessive, adequate or deficient amounts of omega-3 FA during pregnancy and lactation. The 24-day-old offspring in the Excess group, compared to the Control group, had postnatal growth retardation and poor hearing acuity and prolonged neural transmission times as evidenced by the ABR. The Deficient group was intermediate. The current study followed these offspring to see if these poor outcomes persisted into young adulthood. Based on prior findings, we hypothesized that the Excess and Deficient offspring would "catch-up" to the Control offspring by young adulthood. Female Wistar rats received one of the three diet conditions from day 1 of pregnancy through lactation. The three diets were the Control omega-3 FA condition (omega-3/omega-6 ratio approximately 0.14), the Excess omega-3 FA condition (omega-3/omega-6 ratio approximately 14.0) and Deficient omega-3 FA condition (omega-3/omega-6 ratio approximately 0% ratio). The Control diet contained 7% soybean oil; whereas the Deficient and Excess omega-3 FA diets contained 7% safflower oil and 7% fish oil, respectively. One male and female offspring per litter were ABR-tested as young adults using tone pip stimuli of 2, 4, 8 and 16 kHz. The postnatal growth retardation and prolonged neural transmission times in the Excess and Deficient pups had dissipated by young adulthood. In contrast, the Excess group had elevated ABR thresholds (hearing loss) at all tone pip frequencies in comparison to the Control and Deficient groups. The Deficient group had worse ABR thresholds than the

  19. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring.

    PubMed

    Chowdhury, Sabiha S; Lecomte, Virginie; Erlich, Jonathan H; Maloney, Christopher A; Morris, Margaret J

    2016-01-01

    Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID:27563922

  20. Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

    PubMed Central

    Lv, Juanxiu; Zhang, Peiwen; Zhang, Yujuan; Kuang, Hanzhe; Cao, Li; Wu, Conglong; Jiang, Lin; Li, Dawei; Mao, Caiping

    2014-01-01

    Aims: Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin–angiotensin system (RAS) that may mediate cardiac cell death. Methods and Results: Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells. Conclusion: Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway. PMID:23690339

  1. Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring.

    PubMed

    Pinheiro, C R; Moura, E G; Manhães, A C; Fraga, M C; Claudio-Neto, S; Younes-Rapozo, V; Santos-Silva, A P; Lotufo, B M; Oliveira, E; Lisboa, P C

    2015-10-01

    The mesolimbic reward pathway is activated by drugs of abuse and palatable food, causing a sense of pleasure, which promotes further consumption of these substances. Children whose parents smoke are more vulnerable to present addictive-like behavior to drugs and food.We evaluated the association between maternal nicotine exposure during lactation with changes in feeding, behavior and in the dopaminergic reward system. On postnatal day (PN) 2,Wistar rat dams were implanted with minipumps releasing nicotine (N; 6 mg/kg/day, s.c.) or saline (C) for 14 days. On PN150 and PN160, offspring were divided into 4 groups for a food challenge: N and C that received standard chow(SC); and N and C that could freely self-select (SSD) between high-fat and high-sugar diets (HFD and HSD, respectively). Offspring were tested in the elevated plus maze (EPM) and open field (OF) arena on PN152–153. On PN170, offspring were euthanized for central dopaminergic analysis. SSD animals showed an increased food intake compared to SC ones and a preference for HFD. However, N-SSD animals consumed relatively more HSD than C-SSD ones. Regarding behavior, N animals showed an increase in the time spent in the EPM center and a reduction in relative activity in the OF center. N offspring presented lower dopamine receptor (D2R) and transporter (DAT) contents in the nucleus accumbens, and lower D2R in the arcuate nucleus. Postnatal exposure to nicotine increases preference for sugar and anxiety levels in the adult progeny possibly due to a decrease in dopaminergic action in the nucleus accumbens and arcuate nucleus. PMID:26048299

  2. Sex Dimorphism in Late Gestational Sleep Fragmentation and Metabolic Dysfunction in Offspring Mice

    PubMed Central

    Khalyfa, Abdelnaby; Carreras, Alba; Almendros, Isaac; Hakim, Fahed; Gozal, David

    2015-01-01

    Background: Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates. Methods: Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed. Results: Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF. Conclusion: Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood. Citation: Khalyfa A, Carreras A, Almendros I, Hakim F, Gozal D. Sex

  3. Maternal pelvic size, fetal growth and risk of stroke in adult offspring in a large Swedish cohort.

    PubMed

    Heshmati, A; Chaparro, M P; Koupil, I

    2016-02-01

    Earlier research suggests that maternal pelvic size is associated with offspring's stroke risk in later life. We followed 6362 men and women from Uppsala, Sweden, born between 1915 and 1929 from 1964 to 2008 to assess whether maternal pelvic size was associated with incidence of thrombotic stroke (TS), haemorrhagic stroke (HS) and other stroke (OS). Offspring whose mothers had a flat pelvis had lower birth weight and birth-weight-for-gestational-age compared with those who did not. Inverse linear associations of birth-weight-for-gestational-age were observed with TS and OS. Female offspring whose mothers had a flat pelvis had increased risk of TS, but flat pelvis was not associated with other types of stroke. A smaller difference between intercristal and interspinous diameters and a smaller external conjugate diameter were independently associated with HS, whereas no pelvic measurements were associated with OS. We conclude that a smaller pelvis in women may impact the health of their offspring in adulthood. PMID:26441399

  4. N-Acetylcysteine Prevents Programmed Hypertension in Male Rat Offspring Born to Suramin-Treated Mothers.

    PubMed

    Tain, You-Lin; Hsu, Chien-Ning; Lee, Chien-Te; Lin, Yu-Ju; Tsai, Ching-Chou

    2016-07-01

    Adulthood hypertension can be programmed by preeclampsia. Preeclampsia is associated with an imbalance in vasoactive factors, including nitric oxide (NO), hydrogen sulfide (H2S), and renin-angiotensin system (RAS). We examined whether maternal N-acetylcysteine (NAC) therapy prevented maternal suramin treatment-induced programmed hypertension in offspring and explored the effects of this therapy on NO, H2S, and RAS pathways in the kidneys. Pregnant Sprague-Dawley rats were intraperitoneally administered 60 mg/kg suramin alone on Gestational Days 10 and 11 and were treated with or without 1% NAC through drinking water during the entire pregnancy and lactation period. Male offspring were divided into four groups (n = 8-10/group): control, suramin, NAC, and suramin plus NAC. All rat offspring were euthanized at 12 wk of age. Maternal suramin treatment induced programmed hypertension in male offspring, which was prevented by maternal NAC therapy. Suramin-induced programmed hypertension was associated with increased plasma asymmetric dimethylarginine (ADMA, an NO synthase inhibitor) level, decreased plasma l-arginine-to-ADMA ratio, and decreased renal dimethylarginine dimethylaminohydrolase (an ADMA-metabolizing enzyme) activity. Protective effects of NAC against suramin-induced programmed hypertension were associated with an increase in plasma glutathione level, increase in renal 3-mercaptopyruvate sulfurtransferase level, and restoration of suramin-induced reduction in H2S synthesis in the kidneys. Suramin treatment exerted negligible effect on the RAS pathway in the adult male offspring kidneys. Our data suggested interplay among suramin, ADMA-NO pathway, and H2S synthesis pathway in programmed hypertension. Furthermore, NAC administration in pregnant rats with hypertension prevented programmed hypertension in adult offspring. PMID:27251093

  5. Interesterified fat or palm oil as substitutes for partially hydrogenated fat during the perinatal period produces changes in the brain fatty acids profile and increases leukocyte-endothelial interactions in the cerebral microcirculation from the male offspring in adult life.

    PubMed

    Misan, Vanessa; Estato, Vanessa; de Velasco, Patricia Coelho; Spreafico, Flavia Brasil; Magri, Tatiana; Dos Santos, Raísa Magno de Araújo Ramos; Fragoso, Thaiza; Souza, Amanda S; Boldarine, Valter Tadeu; Bonomo, Isabela T; Sardinha, Fátima L C; Oyama, Lila M; Tibiriçá, Eduardo; Tavares do Carmo, Maria das Graças

    2015-08-01

    We investigated whether maternal intake of normolipidic diets with distinct fatty acid (FA) compositions alters the lipidic profile and influences the inflammatory status of the adult offsprings׳ brains. C57BL/6 female mice during pregnancy and lactation received diets containing either soybean oil (CG), partially hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or interesterified fat (IG). After weaning, male offspring from all groups received control diet. The FA profile was measured in the offspring׳s brains at post-natal days 21 and 90. Brain functional capillary density as well as leukocyte-endothelial interactions in the cerebral post-capillary venules was assessed by intravital fluorescence microscopy at post-natal day 90. Inflammation signaling was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult offspring. In the 21-day old offspring, the brains of the TG showed higher levels of trans FA and reduced levels of linoleic acid (LA) and total n-6 polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be lower compared to CG. The offspring׳s brains exhibited an altered microcirculation with increased leukocyte rolling in groups TG, PG and IG and in TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of trans FA, palm oil or interesterified fat during pregnancy and lactation can trigger the initial steps of inflammatory pathways in the brain of offspring in adulthood. PMID:25982597

  6. Maternal diet-induced obesity programs cardiovascular dysfunction in adult male mouse offspring independent of current body weight.

    PubMed

    Blackmore, Heather L; Niu, Youguo; Fernandez-Twinn, Denise S; Tarry-Adkins, Jane L; Giussani, Dino A; Ozanne, Susan E

    2014-10-01

    Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet-induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring. PMID:25051449

  7. A Mentor Manual: For Adults Who Work with Pregnant and Parenting Teens.

    ERIC Educational Resources Information Center

    Kanfer, Frederick H.; Englund, Susan; Lennhoff, Claudia; Rhodes, Jean

    Intended for adults working with expectant and new teen mothers, this guide provides techniques and strategies for helping the teen mother develop skills needed to achieve parenting and life goals. The first half of the guide explores the relationship between the adult mentor and teen parent, and steps toward problem solving and positive change.…

  8. Reader-Responses of Pregnant Adolescents and Teenage Mothers to Young Adult Novels Portraying Protagonists with Problems Similar and Dissimilar to the Readers'.

    ERIC Educational Resources Information Center

    Poe, Elizabeth Ann

    Applying reader response theory, a study explored the responses of 19 pregnant adolescents and teenage mothers to two dissimilar young adult novels, one about teenage pregnancy and one about adolescent alcoholism. Quantitative analysis, using a modified version of the Purves-Rippere (1968) system, and qualitative analysis of written answers to…

  9. Prenatal ethanol exposure induces the osteoarthritis-like phenotype in female adult offspring rats with a post-weaning high-fat diet and its intrauterine programming mechanisms of cholesterol metabolism.

    PubMed

    Ni, Qubo; Wang, Linlong; Wu, Yunpeng; Shen, Lang; Qin, Jun; Liu, Yansong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-14

    Osteoarthritis (OA) development is associated with hypercholesterolemia in adults. Our previous study demonstrated that offspring with intrauterine growth retardation (IUGR) due to prenatal ethanol exposure (PEE) had a high risk of developing hypercholesterolemia and metabolic syndrome when fed a post-weaning high-fat diet (HFD). In this study, we examined the changes in articular chondrocytes of IUGR offspring induced by PEE and explored its intrauterine programming mechanisms related to cholesterol metabolism. Using the PEE/IUGR model, serum and tibias from female fetuses and adult female offspring fed a post-weaning HFD were collected and examined for cholesterol metabolism and histology. The results showed that PEE adult offspring manifested significant catch-up growth. Their serum total cholesterol (TCH) and low-density lipoprotein-cholesterol increased and high-density lipoprotein-cholesterol decreased; the osteoarthritis-like phenotype and an increased TCH content were observed in articular cartilage; and the expression of insulin-like growth factor1 (IGF1) and cholesterol efflux pathway, including ATP-binding-cassette transporter A1 and liver X receptor, was reduced. The expression of IGF1 and cholesterol efflux pathway was also lower in the PEE fetuses. This study showed PEE could induce an enhanced susceptibility to HFD-induced OA in adult female IUGR offspring. The underlying mechanism related to cholesterol accumulation in cartilage mediated by intrauterine programming. PMID:26220516

  10. MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

    PubMed

    Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

    2015-08-01

    Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory

  11. Uteroplacental insufficiency programmes vascular dysfunction in non-pregnant rats: compensatory adaptations in pregnancy.

    PubMed

    Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Dragomir, Nicoleta M; Parry, Laura J; Wlodek, Mary E

    2012-07-15

    Intrauterine growth restriction is a risk factor for cardiovascular disease in adulthood. We have previously shown that intrauterine growth restriction caused by uteroplacental insufficiency programmes uterine vascular dysfunction and increased arterial stiffness in adult female rat offspring. The aim of this study was to investigate vascular adaptations in growth restricted female offspring when they in turn become pregnant. Uteroplacental insufficiency was induced in WKY rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of pregnancy. F0 pregnant females delivered naturally at term. F1 Control and Restricted offspring were mated at 4 months of age and studied on day 20 of pregnancy. Age-matched non-pregnant F1 Control and Restricted females were also studied. Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of all four groups. Collagen and elastin fibres were quantified using polarized light microscopy and qRT-PCR. F1 Restricted females were born 10–15% lighter than Controls (P <0.05). Non-pregnant Restricted females had increased uterine and renal artery stiffness compared with Controls (P <0.05), but this difference was abolished at day 20 of pregnancy. Vascular smooth muscle and endothelial function were preserved in all arteries of non-pregnant and pregnant Restricted rats. Collagen and elastin content were unaltered in uterine arteries of Restricted females. Growth restricted females develop compensatory vascular changes during late pregnancy, such that region-specific vascular deficits observed in the non-pregnant state did not persist in late pregnancy. PMID:22586217

  12. High intensity exercise during pregnancy of rats. Effects on mother and offspring.

    PubMed

    Denadai, B S; Piçarro, I da C; Madjian, S; Bergamaschi, C T; Santos, V C; da Silva, A C; Russo, A K

    1994-11-01

    We see in this study the effect of high intensity exercise (90% VO2 max) in pregnant rats and their offspring depending on the length of pregnancy. The findings were compared with those obtained for sedentary pregnant rats and non-pregnant rats for similar exercise. This allowed for analysing the isolated effects of exercise (against the sedentary non-pregnant rat control group), of pregnancy and of the interaction between the two factors. For checking the effect of the length of pregnancy, each group of rats was subdivided into those with pregnancy terminated or sacrificed on the seventh, fourteenth or twentieth day of the experiment. VO2 max, post-exertion blood lactic acid level, body weight gain, food intake, feed efficiency, glucose, triglyceride, total cholesterol, total protein and albumin plasmatic concentrations in adult rats, and weight and number of offspring of pregnant rats were determined. Pregnancy increased weight gain and feed efficiency from the first week of the study, accompanied by a greater food intake (from the twelfth day). In the group of pregnant rats subjected to exercise, there was a reduction in weight gain percentage and feed efficiency in the first and third weeks, staying the same in the second week. A greater food intake during the period accompanied this recovery in the second week. In the group of non-pregnant rats subjected to exercise, food intake did not vary. As the weight gain percentage was less in relation to the non-pregnant control group, feed efficiency decreased. Pregnancy induced a drop in blood sugar level starting in the second week, and the exercise performed during pregnancy did not change this behavior. Pregnancy produced, however, an increase in plasmatic concentration of triglycerides and total cholesterol during the third week of pregnancy. Exercise performed by pregnant rats also did not change this behavior, but the increase observed in the third week was less. Exercise performed by non-pregnant rats did not

  13. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood

    PubMed Central

    de Fante, Thaís; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; de Souza, Monique; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  14. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood.

    PubMed

    Fante, Thaís de; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; Souza, Monique de; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  15. [Nutrition of pregnant women: consequences for fetal growth and adult diseases].

    PubMed

    Weber, M; Ayoubi, J-M; Picone, O

    2015-01-01

    The developmental origins of human adult disease are thought to be secondary to a perturbation of the embryonic or fetal development, which leads to metabolic disorders such as diabetes or hypertension at adulthood. Maternal undernutrition or overnutrition, repeated glucocorticosteroids administered to the mother, or placental dysfunction are the most frequently considered causal factors. Therefore, it is necessary that the pediatrician is aware of these phenomena, as this knowledge may contribute to the prevention of adult diseases. Little is known yet, however, on the pathophysiological or epigenetic mechanisms that lead to theses observations, and more studies are needed both in humans and animal models. PMID:25440770

  16. Young Offspring at Genetic Risk of Adult Psychoses: The Form of the Trajectory of IQ or Memory May Orient to the Right Dysfunction at the Right Time

    PubMed Central

    Maziade, Michel; Rouleau, Nancie; Cellard, Caroline; Battaglia, Marco; Paccalet, Thomas; Moreau, Isabel; Gagnon, Valérie; Gingras, Nathalie; Marino, Cecilia; Gilbert, Elsa; Roy, Marc-André; Mérette, Chantal

    2011-01-01

    Objective Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations? Methods In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members. We then identified 400 adult members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring (of an affected parent) aged 7 to 22, who were administered a neuropsychological battery. We then constructed cross-sectional trajectories that were compared to those of controls. Results The childhood IQ deficit displayed a stability until young adulthood. The delay in visual memory exhibited a non-linear two-stage trajectory: a lagging period during childhood followed by a recuperation period from adolescence until adulthood, as supported by a significant Group x Age Periods interaction. No data suggested deterioration between 7 and 22. Conclusion In these offspring at genetic risk, the developmental trajectory of global IQ impairment may not apply to specific domains of cognition such as episodic memory. Different cognitive dysfunctions would mark different developmental courses. The shape of the trajectories might itself have a meaning and provide empirical leads for targeting the right dysfunction at the right time in future prevention research. PMID:21559460

  17. Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring.

    PubMed

    de Oliveira, Júlio Cezar; Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; Franco, Claudinéia Conationi da Silva; Pavanello, Audrei; Torrezan, Rosana; Natali, Maria Raquel Marçal; Lisboa, Patrícia Cristina; Mathias, Paulo Cezar de Freitas; de Moura, Egberto Gaspar

    2016-05-01

    Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071

  18. Early bi-parental separation or neonatal paternal deprivation in mandarin voles reduces adult offspring paternal behavior and alters serum corticosterone levels and neurochemistry.

    PubMed

    Yu, Peng; Zhang, Hui; Li, Xibo; He, Fengqin; Tai, Fadao

    2015-07-01

    Although the effect of early social environments on maternal care in adulthood has been examined in detail, few studies have addressed the long-term effect on paternal care and its underlying neuroendocrine mechanisms. Here, using monogamous mandarin voles (Microtus mandarinus) that show high levels of paternal care, the effects of early bi-parental separation (EBPS) or neonatal paternal deprivation (NPD) on adult paternal behavior, serum corticosterone levels, and receptor mRNA expression in the nucleus accumbens (NAcc) and medial preoptic area (MPOA) were investigated. Compared to the parental care group (PC), we found that EBPS reduced crouching behavior and increased inactivity, self-grooming, and serum corticosterone levels in adult offspring; and NPD significantly reduced retrieval behavior and increased self-grooming behavior of offspring at adulthood. EBPS displayed more dopamine type I receptor (D1R) mRNA expression in the NAcc, but less oxytocin receptor (OTR) mRNA expression than PC in the MPOA. Both EBPS and NPD exhibited more mRNA expression of estrogen receptor alpha (ERα) than PC in the MPOA. In the EBPS group, increased serum corticosterone concentration was closely associated with reduced crouching behavior, and reduced expression of OTR was closely associated with altered crouching behavior and increased D1R expression. Our results provide substantial evidence that EBPS or NPD has long-term consequences and reduces paternal behavior in adult animals. Importantly the oxytocin system in the MPOA might interact with NAcc dopamine systems to regulate paternal behavior and EBPS may affect interactions between the MPOA and NAcc. PMID:26012712

  19. Offspring, 1995.

    ERIC Educational Resources Information Center

    Offspring, 1995

    1995-01-01

    These two 1995 issues of the journal "Offspring," a publication of the Michigan Council of Cooperative Nursery Schools, cover a variety of topics familiar to nursery school and day care providers including the mission of the publication. Articles are short pieces useful to practitioners and are frequently accompanied by classroom activities.…

  20. Offspring, 1996.

    ERIC Educational Resources Information Center

    Rosenthal, Marilynn, Ed.; And Others

    1996-01-01

    These two 1996 issues of the journal "Offspring," a publication of the Michigan Council of Cooperative Nursery Schools, cover a variety of topics familiar to nursery school and day care providers and pertinent to the mission of the publication. Articles are short pieces useful to parents, teachers, and others and aim to provide a forum for views…

  1. Sex-Specific Programming of Hypertension in Offspring of Late Gestation Diabetic Rats

    PubMed Central

    Katkhuda, Ragheed; Peterson, Emily S.; Roghair, Robert D.; Norris, Andrew W.; Scholz, Thomas D.; Segar, Jeffrey L.

    2013-01-01

    Background The intrauterine environment strongly influences adult disease susceptibility. We utilized a rat model of third trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness. Methods Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 day) and partially controlled with insulin injections. Hemodynamic function was evaluated in 6–12 month old offspring. Results Male but not female offspring of diabetic mothers (ODM) had significantly increased blood pressure compared to controls, heart rate was similar. For both sexes, heart rate baroreflex responses were similar as were in vivo hemodynamic responses to angiotensin II, NOS inhibition and ganglionic blockade. Aortic contractility to angiotensin II was similar in both groups. NOS inhibition and the Cu/Zn superoxide dismutase (SOD) inhibitor diethyldithiocarbamate but not the SOD-mimetic Tempol significantly increased contractile responses to angiotensin II in controls but not ODM. NADPH stimulated superoxide production was greater in male ODM than controls (p<0.05). Conclusions Exposure to hyperglycemia in utero results in sex specific cardiovascular changes in adult offspring. Impaired NO - reactive oxygen species signaling may play a significant role in the hemodynamic phenotype of ODM. PMID:22805998

  2. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to {delta}{sup 9}-tetrahydrocannabinol

    SciTech Connect

    Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo; Lourdusamy, Anbarasu; Soverchia, Laura; Hardiman, Gary; Campolongo, Patrizia; Cuomo, Vincenzo; Ciccocioppo, Roberto

    2007-08-15

    The present study evaluated the consequences of perinatal {delta}{sup 9}-tetrahydrocannabinol ({delta}{sup 9}-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB{sub 1} receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with {delta}{sup 9}-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, {delta}{sup 9}-THC, or EtOH + {delta}{sup 9}-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to {delta}{sup 9}-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB{sub 1} receptor antagonists may represent interesting

  3. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  4. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.

    PubMed

    Batinić, Bojan; Santrač, Anja; Divović, Branka; Timić, Tamara; Stanković, Tamara; Obradović, Aleksandar Lj; Joksimović, Srđan; Savić, Miroslav M

    2016-02-15

    Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively. PMID:26620494

  5. A New and Fast Technique to Generate Offspring after Germ Cells Transplantation in Adult Fish: The Nile Tilapia (Oreochromis niloticus) Model

    PubMed Central

    Lacerda, Samyra M. S. N.; Batlouni, Sergio R.; Costa, Guilherme M. J.; Segatelli, Tânia M.; Quirino, Bruno R.; Queiroz, Bruno M.; Kalapothakis, Evanguedes; França, Luiz R.

    2010-01-01

    Background Germ cell transplantation results in fertile recipients and is the only available approach to functionally investigate the spermatogonial stem cell biology in mammals and probably in other vertebrates. In the current study, we describe a novel non-surgical methodology for efficient spermatogonial transplantation into the testes of adult tilapia (O. niloticus), in which endogenous spermatogenesis had been depleted with the cytostatic drug busulfan. Methodology/Principal Findings Using two different tilapia strains, the production of fertile spermatozoa with donor characteristics was demonstrated in adult recipient, which also sired progeny with the donor genotype. Also, after cryopreservation tilapia spermatogonial cells were able to differentiate to spermatozoa in the testes of recipient fishes. These findings indicate that injecting germ cells directly into adult testis facilitates and enable fast generation of donor spermatogenesis and offspring compared to previously described methods. Conclusion Therefore, a new suitable methodology for biotechnological investigations in aquaculture was established, with a high potential to improve the production of commercially valuable fish, generate transgenic animals and preserve endangered fish species. PMID:20505774

  6. Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex specific visceral hypersensitivity in offspring

    PubMed Central

    Winston, John H.; Li, Qingjie; Sarna, Sushil K.

    2014-01-01

    Background Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. Methods We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. Results CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. Conclusion & Inferences The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients. PMID:24588943

  7. Impaired hypothalamic mTOR activation in the adult rat offspring born to mothers fed a low-protein diet.

    PubMed

    Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Pérez García, Georgina; Matos, Rhowena J B; de Sa Braga Oliveira, André; Manhães de Castro, Raul; Bolaños-Jiménez, Francisco

    2013-01-01

    Several epidemiological and experimental studies have clearly established that maternal malnutrition induces a high risk of developing obesity and related metabolic diseases in the offspring. To determine if altered nutrient sensing might underlie this enhanced disease susceptibility, here we examined the effects of perinatal protein restriction on the activation of the nutrient sensor mTOR in response to acute variations in the nutritional status of the organism. Female Wistar rats were fed isocaloric diets containing either 17% protein (control) or 8% protein (PR) throughout pregnancy and lactation. At weaning offspring received standard chow and at 4 months of age the effects of fasting or fasting plus re-feeding on the phosphorylation levels of mTOR and its downstream target S6 ribosomal protein (rpS6) in the hypothalamus were assessed by immuno-fluorescence and western blot. Under ad libitum feeding conditions, PR rats exhibited decreased mTOR and rpS6 phosphorylation in the arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei. Moreover, the phosphorylation of mTOR and rpS6 in these hypothalamic nuclei decreased with fasting in control but not in PR animals. Conversely, PR animals exhibited enhanced number of pmTOR imunostained cells in the paraventricular nucleus (PVN) and fasting decreased the activation of mTOR in the PVN of malnourished but not of control rats. These alterations occurred at a developmental stage at which perinatally-undernourished animals do not show yet obesity or glucose intolerance. Collectively, our observations suggest that altered hypothalamic nutrient sensing in response to an inadequate foetal and neonatal energetic environment is one of the basic mechanisms of the developmental programming of metabolic disorders and might play a causing role in the development of the metabolic syndrome induced by malnutrition during early life. PMID:24040371

  8. Unhappiness with the Fetal Gender is associated with Depression in Adult Pregnant Women Attending Prenatal Care in a Public Hospital in Durango, Mexico

    PubMed Central

    Alvarado-Esquivel, Cosme; Sifuentes-Alvarez, Antonio; Salas-Martinez, Carlos

    2016-01-01

    Depression during pregnancy has been scantily studied in Mexican women. We aimed to determine the prevalence and correlates of depression in adult pregnant women attending a public hospital in the northern Mexican city of Durango, Mexico. Through a cross-sectional study design, we assessed depression in 270 adult pregnant women attended for prenatal care in a public hospital using a validated Mexican version of the Edinburg Postnatal Depression Scale in pregnancy and further confirmation by a psychiatric evaluation using the DSM-IV criteria for depression. Prevalence association with socio-demographic, clinical and psychosocial characteristics of the pregnant women was also investigated. Of the 270 pregnant women studied, 101 (37.4%) had EPDS scores equal to or higher than nine. Depression was confirmed in 56 (20.7%) women. Of them, 42 suffered from minor depression and 14 from major depression. Multivariate analysis of socio-demographic, clinical and psychosocial characteristics of the women showed that depression was associated with depression before pregnancy (OR = 3.36; 95% CI: 1.20-9.40; P=0.02), anxiety during pregnancy (OR = 9.38; 95% CI: 1.87-46.96; P=0.006), smoking (OR = 25.05; 95% CI: 1.77-353.07; P=0.01), unhappy with the fetal sex (OR = 8.53; 95% CI: 2.46-29.48; P<0.001), and unintended pregnancy (OR = 2.90; 95% CI: 1.07-7.86; P=0.03). Results indicate that about one fifth of the pregnant women studied had confirmed depression. This is the first report of an association of prenatal depression with unhappiness with the fetal sex. Factors associated with prenatal depression found in this study may help for the optimal design of preventive measures against prenatal depression. PMID:27127452

  9. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    PubMed Central

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification. PMID:26696906

  10. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation

    PubMed Central

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  11. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation.

    PubMed

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  12. Pregnant Women Experiencing IPV: Impact of Supportive and Non-Supportive Relationships with their Mothers and Other Supportive Adults on Perinatal Depression: A Mixed Methods Analysis

    PubMed Central

    Bhandari, Shreya; Bullock, Linda F. C.; Bair-Merritt, Megan; Rose, Linda; Marcantonio, Kristin; Campbell, Jacquelyn C.; Sharps, Phyllis

    2015-01-01

    The current study explored the views of women experiencing interpersonal violence (IPV) and their relationship with their mothers or other supportive adult, and determines how this relationship affected perinatal depressive symptoms. The sample consisted of 30 urban and rural pregnant women enrolled in a larger ongoing randomized controlled trial. Data from quantitative instruments that measured depressive symptoms were examined in combination with qualitative interview data collected at baseline and six months post-natal. Women describing positive relationships with their mothers or another supportive adult reported statistically significant lower depressive symptoms scores (p < .05). PMID:23215984

  13. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT₂A and mGlu₂ receptors in the adult offspring.

    PubMed

    Moreno, José L; Kurita, Mitsumasa; Holloway, Terrell; López, Javier; Cadagan, Richard; Martínez-Sobrido, Luis; García-Sastre, Adolfo; González-Maeso, Javier

    2011-02-01

    Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT(2A) receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu(2/3) agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT(2A) and mGlu(2) receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT(2A) receptor is upregulated and the mGlu(2) receptor is downregulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT(2A) receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos, egr-1, and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia. PMID:21289196

  14. Maternal investment, life-history strategy of the offspring and adult chronic disease risk in South Asian women in the UK

    PubMed Central

    Wells, Jonathan C.K.; Yao, Pallas; Williams, Jane E; Gayner, Rebecca

    2016-01-01

    Background and objectives: Patterns of development predict cardiovascular disease (CVD) risk, and ethnic differences therein, but it remains unclear why apparently ‘adaptive plasticity’ in early life should generate health costs in later life. We hypothesized that offspring receiving low maternal investment during fetal life, the primary period of organogenesis, should predict a shorter reproductive career and develop a fast life-history strategy, prioritizing reproduction over growth and homeostatic maintenance. Methodology: We studied 58 young adult South Asian women living in the UK, a group with high susceptibility to CVD. We obtained gestational age, birth weight (BW) and menarcheal age by recall and measured anthropometry, body composition, resting metabolic rate (RMR) and blood pressure (BP). Results: BW and gestational age were inversely associated with menarcheal age, indicating that lower maternal investment is associated with faster maturation. Menarcheal age was positively associated with height but inversely with adiposity, indicating that rapid maturation prioritizes lipid stores over somatic growth. BW was inversely associated with BP, whereas adiposity was positively associated, indicating that lower maternal investment reduces BP homeostasis. BW was positively associated with RMR, whereas menarche was inversely associated, indicating that maternal investment influences adult metabolism. Conclusions and implications: Supporting our hypothesis, low maternal investment promoted faster life histories, demonstrated by earlier menarche, reduced growth and elevated adiposity. These traits were associated with poorer BP regulation. This is the first study demonstrating strategic adjustment of the balance between reproduction and metabolic health in response to the level of maternal investment during fetal life. PMID:26988862

  15. Interaction of recalled parental ADHD symptoms and rearing behavior with current attachment and emotional dysfunction in adult offspring with ADHD.

    PubMed

    Edel, Marc-Andreas; Juckel, Georg; Brüne, Martin

    2010-06-30

    Research into attachment and emotion regulation has shown that children with ADHD are at risk of developing attachment disorders and emotion regulation disturbances, which in part may be due to the rearing style of their parents. No such data exists for adults with persistent ADHD. We hypothesized that current attachment style and emotion processing of adult patients with ADHD may be influenced by the presence of parental ADHD symptoms when the now adult patients were children, assuming that ADHD symptoms of parents have an impact on their parenting style. We examined recalled parental ADHD symptoms and rearing style as well as current attachment and emotion regulation abilities in a sample of 73 adults with ADHD using several self-rating instruments. Recalled prevalence of ADHD symptoms in the mother, and less so in the father, of adult patients with ADHD was significantly associated with partly adverse parental rearing styles, current attachment problems in romantic partnerships and emotion regulation disturbances compared with adult ADHD patients without possibly affected parent. ADHD symptoms in parents of children with ADHD may present a risk factor for attachment problems and poor emotion regulation when ADHD children are grown. PMID:20452044

  16. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

    PubMed Central

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-01-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi–Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

  17. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

    PubMed Central

    Hallam, Megan C.; Reimer, Raylene A.

    2016-01-01

    The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation. PMID:26784224

  18. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

    PubMed

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-05-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

  19. Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring.

    PubMed

    Singh, K P; Singh, Manoj Kr; Singh, Manish

    2016-08-01

    A tremendous increase has been documented in the recent past in prescribing second generation atypical antipsychotic drugs (AAPDs) to the pregnant women with psychosis, considering their reproductive and teratogenic safety. Among AAPDs, risperidone (RIS) ranked third after olanzapine (OLZ) and quetiapine (QUE) used during pregnancy, as OLZ is associated to substantial weight gain in adults and offspring. Although teratogenic safety of RIS has been established, its potential role in developmental neurotoxicity and related neurobehavioral impairments in adolescents has not been documented so far. Therefore, present study has been undertaken to elucidate the effect of prenatal exposure to risperidone (RIS) on developmental neurotoxicity and apoptotic neurodegeneration in neocortical region of fetal brain; and related functional sequelae in young rat offspring. The pregnant Wistar rats were exposed to RIS at 0.8, 1.0 and 2.0mg/kg, at equivalent therapeutic doses, orally from GD 6 to 21. Half of the pregnant rats were sacrificed and their brains were collected, weighed, and processed for neurohistopathological and apoptotic neurodegenerative evaluation. The remaining dams were allowed to deliver naturally, and their offspring were reared up to 10 weeks for neurobehavioral study. Prenatal exposure to RIS induced significant stunting of fetal body and brain weight, substantial reduction in the thickness of neocortical layers and apoptotic neurodegeneration in fetal brains, and delayed postnatal development and growth of the offspring; as well as long- lasting impact on anxiety like impaired behavioral responses on explorative mazes. Therefore, health care providers should be careful in prescribing atypical antipsychotics in general and RIS in particular, to the pregnant psychotic population. PMID:27184437

  20. Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

  1. Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction

    PubMed Central

    Jones, Karen L.; Smith, Ryan M.; Edwards, Kristin S.; Givens, Bennet; Beversdorf, David Q.

    2010-01-01

    Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a 3-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring. PMID:20470877

  2. Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

    PubMed

    Mao, Zhenxing; Xia, Wei; Chang, Huailong; Huo, Wenqian; Li, Yuanyuan; Xu, Shunqing

    2015-11-01

    Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. PMID:26276081

  3. Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague-Dawley offspring.

    PubMed

    Panos, John J; Law, C Delbert; Ferguson, Sherry A

    2014-01-01

    MPH is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Here, Sprague-Dawley rats were orally treated 3 ×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14 mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs) 1-21, all offspring/litter were orally treated 2 ×/day with the same dose. Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed. T3, T4, E2, testosterone, LH and corticosterone were measured at PND 22. Separate pregnant dams and resulting litters were used for serum MPH measurements. MPH treatment had mild, but significant, effects on gestational body weight and food intake. Birth weight of high MPH offspring was 5% more than controls (p<0.0500). Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more (p<0.0094), low MPH females weighed more (p<0.0001), while high MPH females weighed less (p<0.0397). PND 22 serum E2 levels were significantly decreased (20-25%) in high MPH males and females (p<0.0500). Behavioral performance was unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were within the range produced by therapeutic MPH doses in adults; however, offspring levels in all groups were substantially higher. These results indicate that developmental MPH treatment has mild effects on gestational body weight and food intake and offspring preweaning body weight. Potential functional consequences of decreased serum E2 levels are not clear, but may impact later behavior or physiology. PMID:24444667

  4. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and its implication in executive functions in adult offspring of alcohol-dependent probands.

    PubMed

    Benzerouk, Farid; Gierski, Fabien; Gorwood, Philip; Ramoz, Nicolas; Stefaniak, Nicolas; Hübsch, Bérengère; Kaladjian, Arthur; Limosin, Frédéric

    2013-06-01

    Impairment of executive functions (EFs) mediated by the prefrontal lobe is regarded as a cognitive endophenotype of alcohol dependence, being observed both in probands and in healthy offspring. Given its impact on the anatomy of the prefrontal cortex, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may well be involved in this specific endophenotype. Forty-six healthy adult children of alcoholics (HACA) and 82 healthy controls (HC) took part in the study. All the participants were assessed with the Diagnostic Interview for Genetic Studies, and their family histories of alcohol and substance use were assessed with the Family Informant Schedule and Criteria. The Trail Making Test, Arithmetic Switching Task, Stroop Color-Word Test and Wisconsin Card Sorting Test were administered to assess EFs. An overall executive factor score was calculated using factorial analyses. Genotyping of the BDNF Val66Met polymorphism was performed using the TaqMan® allelic discrimination assay. HACA had significantly lower EFs performance than HC. Genetic analysis showed that BDNF genotype distributions were in Hardy-Weinberg equilibrium in the HACA and HC. Genotype and allele distributions did not differ significantly between the two groups. Participants with the Met allele performed significantly more poorly than participants with the Val allele, and a group by allele interaction was observed, the BDNF Met allele being associated with a poorer executive factor score in the HACA group. These results suggest that the BDNF Val66Met polymorphism may contribute to alcohol dependence vulnerability via lower EFs performance. PMID:23582695

  5. PROGRAMMING OF GROWTH, INSULIN RESISTANCE AND VASCULAR DYSFUNCTION IN OFFSPRING OF LATE GESTATION DIABETIC RATS

    PubMed Central

    Segar, Emily M.; Norris, Andrew W.; Yao, Jian-Rong; Hu, Shanming; Koppenhafer, Stacia L.; Roghair, Robert D.; Segar, Jeffrey L.; Scholz, Thomas D.

    2010-01-01

    The offspring of diabetic mothers (ODM) have an increased risk of developing metabolic and cardiovascular dysfunction. However, few studies have focused on susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late-gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg, i.p.) in pregnant rats on gestational day 13 and partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (p < 0.05), however, by 6 months of age this trend reversed. Hyperinsulinemic-euglycemic clamp revealed insulin resistance in male ODM (p < 0.05). In 6-8 mo old female ODM, aortas showed significantly enhanced contractility to potassium chloride (KCl), endothelin-1 (ET-1) and noradrenaline (NA). No differences in responses to endothelin-1 and noradrenaline were apparent with co-administration of NG-nitro-L-arginine (L-NNA). Relaxation to acetylcholine but not nitroprusside was significantly impaired in female ODM. In contrast, males displayed no between group differences in response to vasoconstrictors while relaxation to nitroprusside and acetylcholine was greater in ODM compared to control animals. Thus, development of diabetes during pregnancy programs gender specific insulin resistance and vascular dysfunction in adult offspring. PMID:19203348

  6. Perinatal exposure to 4-nonylphenol affects adipogenesis in first and second generation rats offspring.

    PubMed

    Zhang, Hong-Yu; Xue, Wei-Yan; Li, Yuan-Yuan; Ma, Yue; Zhu, Ying-Shuang; Huo, Wen-Qian; Xu, Bing; Xia, Wei; Xu, Shun-Qing

    2014-03-01

    Maternal exposure to 4-nonylphenol (4-NP) during pregnancy was shown to alter adipogenesis in rodents, yet whether the effects are restricted to 4-NP-exposed offspring only or can be transmitted to the next generation are not known. Pregnant Wistar rats received either vehicle or 4-NP (5, 25 and 125μg/kg/day) from gestation to postnatal day 21. F1 pups were subjected to blood biochemistry tests, or killed to obtain their gonadal fat to determine gene expression. Some F1 adult female rats were mated with F1 males from control group to obtain F2 pups, but without any exposure to 4-NP in the perinatal stage. F2 pups underwent studies similar to those performed on F1 pups. Serum total cholesterol, leptin levels were significantly elevated, the quantity and size of fat cells were increased, gene expression of key regulators of adipogenesis and lipogenic pathway of fat tissue were perturbed by 4-NP (p<0.05 or p<0.01). In addition, the expression of mRNA levels and protein of ERα were downregulated in adipose tissue in the two generation offspring. Perinatal exposure to 4-NP affects the adipogenesis in both male and female F1 offspring, and this effect can be progressed to the F2 offspring through the maternal line. PMID:24388992

  7. Prenatal Exposure to Lamotrigine: Effects on Postnatal Development and Behaviour in Rat Offspring

    PubMed Central

    Sathiya, Sekar; Ganesh, Murugan; Kalaivani, Periyathambi; Ranju, Vijayan; Janani, Srinivasan; Pramila, Bakthavachalam; Saravana Babu, Chidambaram

    2014-01-01

    Use of antiepileptic drugs (AEDs) in pregnancy warrants various side effects and also deleterious effects on fetal development. The present study was carried out to assess the effects of prenatal exposure to lamotrigine (LTG) on postnatal development and behavioural alterations of offspring. Adult male and female Sprague Dawley rats weighing 150–180 g b. wt. were allowed to copulate and pregnancy was confirmed by vaginal cytology. Pregnant rats were treated with LTG (11.5, 23, and 46 mg/kg, p.o) from gestational day 3 (GND 3) and this treatment continued till postnatal day 11 (PND 11). Offspring were separated from their dam on day 21 following parturition. LTG, at 46 mg/kg, p.o, produced severe clinical signs of toxicity leading to death of dam between GND 15 and 17. LTG, at 11.5 and 23 mg/kg, p.o, showed significant alterations in offspring's incisors eruption and vaginal opening when compared to age matched controls. LTG (23 mg/kg, p.o) exposed female offspring expressed hyperactive behaviour and decreased GABA-A receptor expression when compared to control rats. These results reveal that prenatal exposure to LTG may impart differential postnatal behavioural alterations between male and female rats which paves way for further investigations. PMID:24967313

  8. Prenatal exposure to selective serotonin reuptake inhibitors (SSRI) increases aggression and modulates maternal behavior in offspring mice.

    PubMed

    Svirsky, Natali; Levy, Sigal; Avitsur, Ronit

    2016-01-01

    Selective serotonin reuptake inhibitors (SSRI) are commonly prescribed antidepressant drugs in pregnant women. SSRIs cross the placental barrier and affect serotonergic neurotransmission in the fetus. Although no gross SSRI-related teratogenic effects were reported, infants born following prenatal exposure to SSRIs are at higher risk for various developmental abnormalities. The aim of this study was to examine the effects of prenatal SSRI on social and maternal behavior in mice. To this end, pregnant female dams were exposed to saline or fluoxetine (FLX) throughout pregnancy, and the behavior of the offspring was examined. The results indicate that in utero FLX increased aggression in adult males and delayed emergence of maternal behavior in adult females. Social exploration and recognition memory were not affected by prenatal FLX exposure. These findings support the notion that alterations in the development of serotonergic pathways following prenatal exposure to SSRIs are associated with changes in social and maternal behavior throughout life. PMID:26336834

  9. Comparing Sexuality Communication Among Offspring of Teen Parents and Adult Parents: a Different Role for Extended Family

    PubMed Central

    Tracy, Allison J.; Richer, Amanda M.; Erkut, Sumru

    2016-01-01

    This brief report examined teenagers’ sexuality communication with their parents and extended families. It compared who teens of early parents (those who had children when they were adolescents) and teens of later parents (those who were adults when they had children) talk to about sex. Eighth grade students (N=1281) in 24 schools completed survey items about their communication about sex. Structural equation modeling was used to predict communication profiles, while adjusting for the nesting of students within schools. After controlling for teens’ age, gender, race/ethnicity, grades, parent/guardian closeness, and social desirability of survey responses, as well as family status and median family income, results showed that teens of early (teen) parents were more likely than teens of later (adult) parents to talk with both parents and extended family about sex and less likely than later parents to talk only with parents. These findings indicate that realities of teen sexuality communication for teens of early parents may extend beyond a parent-teen model to include extended family. Extended family involvement in educational outreach is a potential untapped resource to support sexual health for teens of early parents. PMID:27499816

  10. Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner

    PubMed Central

    Su, Yixin; Bi, Jianli; Figueroa, Jorge; Chappell, Mark; Rose, James C.

    2015-01-01

    We have shown a sex-specific effect of fetal programming on Na+ excretion in adult sheep. The site of this effect in the kidney is unknown. Therefore, we tested the hypothesis that renal proximal tubule cells (RPTCs) from adult male sheep exposed to betamethasone (Beta) before birth have greater Na+ uptake than do RPTCs from vehicle-exposed male sheep and that RPTCs from female sheep similarly exposed are not influenced by antenatal Beta. In isolated RPTCs from 1- to 1.5-yr-old male and female sheep, we measured Na+ uptake under basal conditions and after stimulation with ANG II. To gain insight into the mechanisms involved, we also measured nitric oxide (NO) levels, ANG II receptor mRNA levels, and expression of Na+/H+ exchanger 3. Basal Na+ uptake increased more in cells from Beta-exposed male sheep than in cells from vehicle-exposed male sheep (400% vs. 300%, P < 0.00001). ANG II-stimulated Na+ uptake was also greater in cells from Beta-exposed males. Beta exposure did not increase Na+ uptake by RPTCs from female sheep. NO production was suppressed more by ANG II in RPTCs from Beta-exposed males than in RPTCs from either vehicle-exposed male or female sheep. Our data suggest that one site of the sex-specific effect of Beta-induced fetal programming in the kidney is the RPTC and that the enhanced Na+ uptake induced by antenatal Beta in male RPTCs may be related to the suppression of NO in these cells. PMID:25834069

  11. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection.

    PubMed

    Santos, Patrícia d'Emery Alves; Lorena, Virgínia Maria Barros de; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; Nascimento, Wheverton Ricardo Correia do; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; Souza, Valdênia Maria Oliveira de

    2016-02-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  12. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

    PubMed Central

    Santos, Patrícia d‘Emery Alves; de Lorena, Virgínia Maria Barros; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; do Nascimento, Wheverton Ricardo Correia; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; de Souza, Valdênia Maria Oliveira

    2016-01-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  13. Effect of selenium on methimazole-induced liver damage and oxidative stress in adult rats and their offspring.

    PubMed

    Sefi, Mediha; Ben Amara, Ibtissem; Troudi, Afef; Soudani, Nejla; Hakim, Ahmed; Zeghal, Khaled Mounir; Boudawara, Tahia; Zeghal, Najiba

    2014-08-01

    This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250 mg L(-1) and standard diet; group III received both MMI (250 mg L(-1), orally) and Se (0.5 mg kg(-1) of diet); group IV received Se (0.5 mg kg(-1) of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage. PMID:23047615

  14. Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring

    PubMed Central

    Wilson, Christina A.; Terry, Alvin V.

    2013-01-01

    Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the α7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

  15. Combined parental obesity augments single-parent obesity effects on hypothalamus inflammation, leptin signaling (JAK/STAT), hyperphagia, and obesity in the adult mice offspring.

    PubMed

    Ornellas, Fernanda; Souza-Mello, Vanessa; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2016-01-01

    We aimed to evaluate the effects of maternal and/or paternal obesity on offspring body mass, leptin signaling, appetite-regulating neurotransmitters and local inflammatory markers. C57BL/6 mice received standard chow (SC, lean groups) or high-fat diet (HF, obese groups) starting from one month of age. At three months, HF mice became obese relative to SC mice. They were then mated as follows: lean mother and lean father, lean mother and obese father, obese mother and lean father, and obese mother and obese father. The offspring received the SC diet from weaning until three months of age, when they were sacrificed. In the offspring, paternal obesity did not lead to changes in the Janus kinase (JAK)/signal transducer and activation of the transcription (STAT) pathway or feeding behavior but did induce hypothalamic inflammation. On the other hand, maternal obesity resulted in increased weight gain, hyperleptinemia, decreased leptin OBRb receptor expression, JAK/STAT pathway impairment, and increased SOCS3 signaling in the offspring. In addition, maternal obesity elevated inflammatory markers and altered NPY and POMC expression in the hypothalamus. Interestingly, combined parental obesity exacerbated the deleterious outcomes compared to single-parent obesity. In conclusion, while maternal obesity is known to program metabolic changes and obesity in offspring, the current study demonstrated that obese fathers induce hypothalamus inflammation in offspring, which may contribute to the development of metabolic syndromes in adulthood. PMID:26485293

  16. Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study

    PubMed Central

    Karmaus, Wilfried; Dimitrov, Plamen; Simeonov, Valeri; Tsolova, Svetla; Bonev, Angel; Georgieva, Rossitza

    2008-01-01

    Background The etiology of Balkan Endemic Nephropathy, (BEN), a tubulointerstitial kidney disease, is unknown. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, similar manifestations are reported to occur in other regions, for instance Tunisia and Sri Lanka. A number of explanations have been stated including lignites, aristolochic acid, ochratoxin A, metals, and metalloids. Etiologic claims are often based on one or a few studies without sound scientific evidence. In this systematic study, we tested whether exposures to metals (cadmium and lead) and metalloids (arsenic and selenium) are related to Balkan Endemic Nephropathy. Methods In 2003/04 we recruited 102 adults whose parents had BEN and who resided in one of three communities (Vratza, Bistretz, or Beli Izvor, Bulgaria). A control group comprised of 99 adults having non-BEN hospitalized parents was enrolled in the study during the same time. We conducted face-to-face interviews, ultrasound kidney measurements, and determined kidney function in two consecutive investigations (2003/04 and 2004/05). Metals and metalloids were measured in urine and blood samples. To assess the agreement between these consecutive measurements, we calculated intraclass correlation coefficients. Repeated measurement data were analyzed using mixed models. Results We found that cadmium and arsenic were associated with neither kidney size nor function. Lead had a significant but negligible effect on creatinine clearance. Selenium showed a weak but significant negative association with two of the four kidney parameters, namely creatinine clearance and β2-microglobulin. It was positively related to kidney length. These associations were not restricted to the offspring of BEN patients. Adding credence to these findings are reports showing comparable kidney effects in animals exposed to selenium. Conclusion The findings of this 2-year follow-up study indicate that metals and metalloids do

  17. Neurocognitive outcomes of children secondary to mild iodine deficiency in pregnant women.

    PubMed

    Caron, Philippe

    2015-07-01

    Iodine deficiency is the most important preventable cause of brain damage worldwide. During pregnancy, severe iodine deficiency causes endemic cretinism, whereas mild-to-moderate iodine deficiency impairs neurocognitive function of the offspring. Numerous reports demonstrate the impact of iodine supplementation on prevention of cretinism, and recent studies evaluate the effects of iodine prophylaxis on neurocognitive development in children of women with mild-to-moderate iodine deficiency. Iodine prophylaxis is generally well tolerated without side effects for the pregnant women and the offspring. In France, the iodine status was recently considered as satisfactory in children and adult population, but regional studies conducted during the last two decades have shown that healthy women are mild-to-moderately iodine deficient during pregnancy. According to recent World Heath Organization guidelines, systematic iodine prophylaxis is recommended in women planning a pregnancy, during gestation and lactation in order to prevent maternal, neonatal and infantile consequences of mild-to-moderate iodine deficiency. PMID:25934357

  18. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    PubMed Central

    Dean, Afshan; van den Driesche, Sander; Wang, Yili; McKinnell, Chris; Macpherson, Sheila; Eddie, Sharon L.; Kinnell, Hazel; Hurtado-Gonzalez, Pablo; Chambers, Tom J.; Stevenson, Kerrie; Wolfinger, Elke; Hrabalkova, Lenka; Calarrao, Ana; Bayne, Rosey AL; Hagen, Casper P.; Mitchell, Rod T.; Anderson, Richard A.; Sharpe, Richard M.

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters. PMID:26813099

  19. ACTH-induced stress response during pregnancy in a viviparous gecko: no observed effect on offspring quality.

    PubMed

    Preest, Marion R; Cree, Alison; Tyrrell, Claudine L

    2005-09-01

    The typical stress response in reptiles involves the release of corticosterone from the adrenal glands. Elevated maternal concentrations of corticosterone in mammals during pregnancy may have deleterious effects on offspring fitness, and recent work has shown a suppression of the hormonal response to stress during pregnancy in rats. Little is known about the influence of reproductive state on the secretion of corticosterone in viviparous reptiles or on the effects of high levels of corticosterone during reproduction on the developing embryos. We examined whether New Zealand common geckos (Hoplodactylus maculatus), pregnant with embryos at stages 34-35 of development, secrete corticosterone in response to adrenocorticotrophic hormone (ACTH) and whether an ACTH-induced increase in maternal corticosterone affects the outcome of pregnancy. Corticosterone concentrations in pregnant lizards increased more than seven-fold over basal levels following injection of ACTH. However, there were no significant effects of elevated corticosterone on the duration or success of pregnancy, or on various morphological measures, growth, or sprint speed of the offspring. This may reflect a lack of sensitivity of relevant embryonic tissues to corticosterone under the conditions of the present experiment or an ability of the embryos to bind, degrade, or restrict placental transport of corticosterone. Future studies should investigate the possibility of corticosteroid effects on other offspring tissues, including effects in adult life. PMID:16106406

  20. THE INFLUENCE OF OBESITY ON BLOOD MERCURY LEVELS FOR U.S. NON-PREGNANT ADULTS AND CHILDREN: NHANES 2007–2010

    PubMed Central

    Rothenberg, Sarah E.; Korrick, Susan A.; Fayad, Raja

    2015-01-01

    Background In animal studies obesity is associated with higher blood and tissue mercury concentrations; however human studies are lacking. Although the mechanism underlying this association is uncertain, obesity may alter the metabolism and distribution of methylmercury. Objectives We determined whether obesity influenced blood mercury levels, the majority of which was methylmercury, for U.S. non-pregnant adults (≥20 years) and children (2–19 years) after controlling for methylmercury intake through fish and shellfish consumption, and other confounders. Methods We completed secondary data analysis of the National Health and Nutrition Examination Survey (NHANES) (2007–2010) for participants who consumed fish/shellfish within 24 hours of blood collection for mercury analysis. Weighted least squares regression models related blood mercury levels (the dependent variable) to methylmercury exposure (μg) from fish consumed in the previous 24 hours, body mass index (BMI) (for adults), BMI z-scores (for children), and other confounders. Results: In adjusted models, blood mercury levels were inversely correlated with BMI for adults [β, 95% confidence interval (CI) = −0.54 (−0.90, −0.18)]. For children, blood mercury levels were inversely correlated with BMI z-scores but the trend was not significant [β (95% CI) = −0.016 (−0.066, 0.035)]. When obese adults or children were compared with those who were overweight/normal weight, blood mercury averaged 22% lower for obese adults (95% CI: −33%, −8.2%), while blood mercury did not differ significantly for obese children [β (95% CI) = −1.7% (−31%, +39%)]. Conclusions After adjusting for the main, if not exclusive, exogenous source of methylmercury exposure (through fish/shellfish intake) and other confounders, our results support potential changes in the metabolism, distribution or excretion of methylmercury with increasing BMI (for adults). PMID:25721244

  1. Ambient temperature and pregnancy influence cortisol levels in female guinea pigs and entail long-term effects on the stress response of their offspring.

    PubMed

    Michel, C L; Chastel, O; Bonnet, X

    2011-05-01

    Mammals generally respond to the important metabolic requirements imposed by thermoregulation and pregnancy by increasing plasma concentrations of glucocorticoid that promote the mobilization of body reserves and enhance energy use by tissues. This study examined the impact of distinct ambient temperatures and reproductive status on cortisol plasma levels in female guinea pigs (Cavia aperea f. porcellus). We also examined cortisol profiles of their offspring. Forty adult females were placed in individual boxes, 20 were exposed to a neutral thermal regime (mean ambient temperature 22.1 ± 1.5 °C) and 20 were maintained under a cool thermal regime (15.1 ± 1.5 °C). Within each treatment, 12 females were pregnant and 8 were non-pregnant. Pregnancy generated a marked elevation of baseline cortisol. Ambient temperature also affected cortisol concentrations. Compared to the pregnant females from the neutral thermal regime, pregnant females maintained under cool conditions exhibited lower baseline levels of cortisol, were less active, but they displayed a greater stress response (i.e. rapid increase of plasma cortisol) following handling. Thermal treatment did not influence reproductive output, reproductive effort, or offspring characteristics. This suggests that pregnant female guinea pigs cope with cool (but not extreme) thermal conditions by reducing activity and baseline cortisol levels, possibly to save energy via an adaptive response. Interestingly, the greater amplitude of the stress response of the cool regime females was also observed in their offspring 2 months after parturition, suggesting that hormonal ambience experienced by the individuals in utero shaped their stress response long after birth. PMID:21334340

  2. Dietary early-life exposure to contaminated eels does not impair spatial cognitive performances in adult offspring mice as assessed in the Y-maze and the Morris water maze.

    PubMed

    Dridi, Imen; Leroy, Delphine; Guignard, Cédric; Scholl, Georges; Bohn, Torsten; Landoulsi, Ahmed; Thomé, Jean-Pierre; Eppe, Gauthier; Soulimani, Rachid; Bouayed, Jaouad

    2014-12-01

    Many environmental contaminants are introduced via the diet and may act as neurotoxins and endocrine disrupters, especially influencing growing organisms in early life. The purpose of this study was to examine whether dietary exposure of dams to fish naturally contaminated with xenobiotics, especially with polychlorinated biphenyls (PCBs) and heavy metals (e.g., mercury and lead), resulted in cognitive function deficits in adult offspring mice. Daily, four groups of dams (n = 10/group) ingested standard diet plus paste with/without eels, during gestation and lactation, from gestational day (GD) six until post natal day (PND) 21 (weaning). Dams orally ingested a standardized amount of eel (0.8 mg kg(-1) d(-1)) containing the six non-dioxin-like (NDL) PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153, and 180) at 0, 85, 216, and 400 ng kg(-1) d(-1). Results showed that early-life exposure to contaminated eels did not (compared to non-exposed controls) impair immediate working memory in the Y-maze in the offspring assessed at PND 38. Furthermore, it did not significantly impact spatial learning and retention memory as measured in the Morris water maze in adult offspring mice (PND 120-123). Our results suggest that perinatal exposure to contaminated eels does not affect spatial cognitive performances, as assessed by the Y-maze and Morris water maze at adult age. Adverse effects of xenobiotics reported earlier might be camouflaged by beneficial eel constituents, such as n-3 fatty acids. However, additional studies are needed to differentiate between potential positive and negative effects following consumption of food items both rich in nutrients and contaminants. PMID:25476192

  3. Adult T-cell leukemia-lymphoma in a pregnant woman diagnosed as a human T-cell lymphotropic virus type 1 carrier.

    PubMed

    Fuchi, Naoki; Miura, Kiyonori; Imaizumi, Yoshitaka; Hasegawa, Hiroo; Yanagihara, Katsunori; Miyazaki, Yasushi; Masuzaki, Hideaki

    2016-03-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia-lymphoma (ATL), which is difficult to cure. In Japan, a nationwide HTLV-1 screening test in pregnant women has been recommended since 2011. A 30-year-old woman was diagnosed as being an HTLV-1 carrier in her previous pregnancy. During the current pregnancy, she had persistent fever and cough. Although she had treatment with antibiotics, peripheral white blood cell count remained high, with an abnormal lymphocyte count. Given that she was an HTLV-1 carrier, she was diagnosed with unfavorable chronic ATL (aggressive ATL) at 12 weeks gestation. After pregnancy termination, her ATL status became favorable chronic ATL (indolent ATL). Therefore, watchful waiting was performed until disease progression. This is the first case report of chronic ATL in early pregnancy, in a woman already diagnosed as an HTLV-1 carrier on screening test. PMID:26663442

  4. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  5. The impact of parental educational trajectories on their adult offspring's overweight/obesity status: a study of three generations of Swedish men and women.

    PubMed

    Chaparro, M P; Koupil, Ilona

    2014-11-01

    The objective of this study was to investigate the impact of grandparental and parental education and parental educational trajectory on their adult offspring's overweight/obesity. We used register data from the Uppsala Birth Cohort Multigenerational Study, based on a representative cohort born in Sweden 1915-1929 (G1). Our sample included 5122 women and 11,204 men who were grandchildren of G1 (G3), their parents (G2), and grandparents. G3's overweight/obesity (BMI≥25 kg/m2) was based on pre-pregnancy weight/height for women before their first birth (average age=26 years), and measured weight/height at conscription for men (average age=18 years). G1's, G2's, and G3's highest educational attainment was obtained from routine registers and classified as low, intermediate, or high based on respective sample distributions. Parental (G2) educational trajectory was defined as change in education between their own and their highest educated parent (G1), classified into 5 categories: always advantaged (AA), upward trajectory (UT), stable-intermediate (SI), downward trajectory (DT), and always disadvantaged (AD). We used hierarchical gender-stratified logistic regression models adjusted for G3's age, education, year of BMI collection, lineage and G2's year of birth and income. Grandparental and parental education were negatively associated with men's odds of overweight/obesity and parental education affected women's overweight/obesity risk. Furthermore, men and women whose parents belonged to the UT, SI, DT, and AD groups had greater odds of overweight/obesity compared to men and women whose parents belonged to the AA group (adjusted for G3's age, year of BMI collection, lineage, and G2's year of birth). These associations were attenuated when further adjusting for parental income and G3's own education. Socioeconomic inequalities can have long-term consequences and impact the health of future generations. For overweight/obesity in concurrent young cohorts, this inequality

  6. Long-term toxicity of reduced graphene oxide nanosheets: Effects on female mouse reproductive ability and offspring development.

    PubMed

    Xu, Shun; Zhang, Zheyu; Chu, Maoquan

    2015-06-01

    Reduced graphene oxide (rGO) nanosheets have emerged as novel materials for cancer therapeutics. Their toxicity has attracted much attention since these nanomaterials may have great potential for clinical cancer treatment. Here we report the influence of rGO exposure on female mouse reproductive ability and offspring development. Mouse dams were injected with small or large rGO nanosheets at different doses and time points, pre- or post-fertilization. The sex hormone levels of adult female mice did not significantly change compared with the control group after intravenous injection with either small or large rGO, even at a high dose (25 mg/kg). Mouse dams could produce healthy offspring after treatment with rGO nanosheets before pregnancy and at an early gestational stage (∼6 days). Despite the successful delivery of offspring, malformed fetuses were found among rGO-injected dam litters. All mice had abortions when injected with low (6.25 mg/kg) or intermediate (12.5 mg/kg) doses at a late gestational stage (∼20 days); the majority of pregnant mice died when injected with the high dose of rGO at this stage of pregnancy. Interestingly, all surviving rGO-injected mouse mothers gave birth to another litter of healthy pups. The results presented in this work are important for a deeper understanding of the toxicity of rGO nanosheets on female reproductivity and their offspring development. PMID:25907052

  7. Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; Van den Hove, Daniel L A

    2016-05-01

    With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 427-438, 2016. PMID:26608001

  8. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    ERIC Educational Resources Information Center

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell…

  9. Maternal lipopolysaccharide treatment differentially affects 5-HT(2A) and mGlu2/3 receptor function in the adult male and female rat offspring.

    PubMed

    Wischhof, Lena; Irrsack, Ellen; Dietz, Frank; Koch, Michael

    2015-10-01

    Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. However, it is still not fully understood which biochemical mechanisms are responsible for the emergence of neuropsychiatric symptoms following prenatal immune activation. The serotonin (5-hydroxytryptamine, 5-HT) and glutamate system have prominently been associated with the schizophrenia pathophysiology but also with the mechanism of antipsychotic drug actions. Here, we investigated the behavioral and cellular response to 5-HT2A and metabotropic glutamate (mGlu)2/3 receptor stimulation in male and female offspring born to lipopolysaccharide (LPS)-treated mothers. Additionally, we assessed protein expression levels of prefrontal 5-HT2A and mGlu2 receptors. Prenatally LPS-exposed male and female offspring showed locomotor hyperactivity and increased head-twitch behavior in response to the 5-HT2A receptor agonist DOI. In LPS-exposed male offspring, the mGlu2/3 receptor agonist LY379268 failed to reduce DOI-induced prepulse inhibition deficits. In LPS-males, the behavioral changes were further accompanied by enhanced DOI-induced c-Fos protein expression and an up-regulation of prefrontal 5-HT2A receptors. No changes in either 5-HT2A or mGlu2 receptor protein levels were found in female offspring. Our data support the hypothesis of an involvement of maternal infection during pregnancy contributing, at least partially, to the pathology of schizophrenia. Identifying biochemical alterations that parallel the behavioral deficits may help to improve therapeutic strategies in the treatment of this mental illness. Since most studies in rodents almost exclusively include male subjects, our data further contribute to elucidating possible gender differences in the effects of prenatal infection on 5-HT2A and mGlu2/3 receptor function. PMID:26051401

  10. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS

    PubMed Central

    LOTH, Eduardo Alexandre; CECATTO, Vanessa; BIAZIM, Samia Khalil; FERREIRA, José Henrique Fermino; DANIELLI, Caroline; GENSKE, Rodrigo Daniel; GANDRA, Rinaldo Ferreira; de FRANCO, Marcello Fabiano

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring. PMID:27049707

  11. Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus.

    PubMed

    Zheng, Yu; Fan, Weidong; Zhang, Xianquan; Dong, Erbo

    2016-01-01

    Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety-like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression. PMID:26890656

  12. Effects of maternal plasmid GHRH treatment on offspring growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To differentiate prenatal effects of plasmid growth hormone-releasing hormone (GHRH) treatment from maternal effects mediated by lactation on long-term growth of offspring, a cross-fostering study was designed. Pregnant sows (n = 12) were untreated (n = 6), or received either a Wt-GHRH (n = 2), or H...

  13. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    PubMed

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake. PMID:27210044

  14. Maternal Drinking and Risky Sexual Behavior in Offspring

    PubMed Central

    De Genna, Natacha M.; Cornelius, Marie D.

    2015-01-01

    Teenage mothers are more likely to use drugs, and their children are more likely to use substances and become pregnant during adolescence. Teenage mothers’ substance use may play a role in the intergenerational risk for adolescent pregnancy. Pregnant adolescents (12–18 years) were seen during pregnancy and postnatal years 6, 10, 14, and 16 (n = 332). Teenage mothers reported on substance use and family characteristics. The offspring reported substance use (starting at age 10) and sexual behavior (ages 14 and 16). Prenatal alcohol exposure was associated with offspring (a) having a risky first sex partner and (b) multiple sex partners in the past year. Heavy maternal drinking during childhood was associated with offspring reports of a risky first sex partner and early teenage pregnancy. Findings from this unique birth cohort have implications for alcohol prevention efforts with girls during and after a teenage pregnancy and interventions to prevent risky sex in high-risk youth. PMID:25156314

  15. Complex life cycles and offspring provisioning in marine invertebrates.

    PubMed

    Marshall, Dustin J; Keough, Michael J

    2006-10-01

    Offspring size can have pervasive effects throughout an organism's life history. Mothers can make either a few large or many small offspring, and the balance between these extremes is determined by the relationship between offspring size and performance. This relationship in turn is thought to be determined by the offspring's environment. Recently, it has become clear that events in one life-history stage can strongly affect performance in another. Given these strong carryover effects, we asked whether events in the larval phase can change the relationship between offspring size and performance in the adult phase. We manipulated the length of the larval period in the bryozoan Bugula neritina and then examined the relationship between offspring size and various parameters of adult performance under field conditions. We found that despite the adult stage being outplanted into identical conditions, different offspring sizes were predicted to be optimal, depending on the experience of those adults as larvae. This work highlights the fact that the strong phenotypic links between life-history stages may result in optimal offspring size being highly unpredictable for organisms with complex life cycles. PMID:21672775

  16. Combo Treatment Protects Pregnant Women, Fetuses from Malaria in Study

    MedlinePlus

    ... gov/medlineplus/news/fullstory_157683.html Combo Treatment Protects Pregnant Women, Fetuses From Malaria in Study Findings ... widely used to treat malaria in adults also protects pregnant women and their fetuses from the disease, ...

  17. Association between maternal age at childbirth and child and adult outcomes in the offspring: a prospective study in five low-income and middle-income countries (COHORTS collaboration)

    PubMed Central

    Fall, Caroline H D; Sachdev, Harshpal Singh; Osmond, Clive; Restrepo-Mendez, Maria Clara; Victora, Cesar; Martorell, Reynaldo; Stein, Aryeh D; Sinha, Shikha; Tandon, Nikhil; Adair, Linda; Bas, Isabelita; Norris, Shane; Richter, Linda M

    2015-01-01

    Summary Background Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low-income and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. We aimed to examine both child and adult outcomes in five LMICs. Methods In this prospective study, we pooled data from COHORTS (Consortium for Health Orientated Research in Transitioning Societies)—a collaboration of five birth cohorts from LMICs (Brazil, Guatemala, India, the Philippines, and South Africa), in which mothers were recruited before or during pregnancy, and the children followed up to adulthood. We examined associations between maternal age and offspring birthweight, gestational age at birth, height-for-age and weight-for-height Z scores in childhood, attained schooling, and adult height, body composition (body-mass index, waist circumference, fat, and lean mass), and cardiometabolic risk factors (blood pressure and fasting plasma glucose concentration), along with binary variables derived from these. Analyses were unadjusted and adjusted for maternal socioeconomic status, height and parity, and breastfeeding duration. Findings We obtained data for 22 188 mothers from the five cohorts, enrolment into which took place at various times between 1969 and 1989. Data for maternal age and at least one outcome were available for 19 403 offspring (87%). In unadjusted analyses, younger (≤19 years) and older (≥35 years) maternal age were associated with lower birthweight, gestational age, child nutritional status, and schooling. After adjustment, associations with younger maternal age remained for low birthweight (odds ratio [OR] 1·18 (95% CI 1·02–1·36)], preterm birth (1·26 [1·03–1·53]), 2-year stunting (1·46 [1·25–1·70]), and failure to complete secondary schooling (1·38 [1·18–1·62]) compared with mothers aged 20–24 years. After adjustment, older maternal age remained

  18. Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

    PubMed Central

    Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms. PMID:25738800

  19. Face-Emotion Processing in Offspring at Risk for Panic Disorder.

    ERIC Educational Resources Information Center

    Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

    2005-01-01

    Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

  20. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia

    PubMed Central

    Arutjunyan, Alexander; Kozina, Lyudmila; Stvolinskiy, Sergey; Bulygina, Yelena; Mashkina, Anna; Khavinson, Vladimir

    2012-01-01

    The offspring of rats with experimental hyperhomocysteinemia caused by alimentary loading with dietary methionine within pregnancy has been studied. Using pinealon (Glu-Asp-Arg) under these conditions was found to result in the offspring cognitive function being improved significantly and their cerebellum neurons becoming more resistant to oxidative stress. This may be proved by the fact that the administration of pinealon to pregnant rats loaded with methionine improved their offspring spatial orientation and learning ability and decreased both reactive oxygen species accumulation and the number of necrotic cells in the population of the neurons isolated from the cerebellum of the offspring developed under the prenatal hyperhomocysteinemia. Our experiments allowed confirming the neuroprotective properties of pinealon, which is in agreement with the previous data obtained by us in vitro. PMID:22567179

  1. Maternal nutrient restriction affects properties of skeletal muscle in offspring

    PubMed Central

    Zhu, Mei J; Ford, Stephen P; Means, Warrie J; Hess, Bret W; Nathanielsz, Peter W; Du, Min

    2006-01-01

    Maternal nutrient restriction (NR) affects fetal development with long-term consequences on postnatal health of offspring, including predisposition to obesity and diabetes. Most studies have been conducted in fetuses in late gestation, and little information is available on the persistent impact of NR from early to mid-gestation on properties of offspring skeletal muscle, which was the aim of this study. Pregnant ewes were subjected to 50% NR from day 28–78 of gestation and allowed to deliver. The longissimus dorsi muscle was sampled from 8-month-old offspring. Maternal NR during early to mid-gestation decreased the number of myofibres in the offspring and increased the ratio of myosin IIb to other isoforms by 17.6 ± 4.9% (P < 0.05) compared with offspring of ad libitum fed ewes. Activity of carnitine palmitoyltransferase-1, a key enzyme controlling fatty acid oxidation, was reduced by 24.7 ± 4.5% (P < 0.05) in skeletal muscle of offspring of NR ewes and would contribute to increased fat accumulation observed in offspring of NR ewes. Intramuscular triglyceride content (IMTG) was increased in skeletal muscle of NR lambs, a finding which may be linked to predisposition to diabetes in offspring of NR mothers, since enhanced IMTG predisposes to insulin resistance in skeletal muscle. Proteomic analysis by two-dimensional gel electrophoresis demonstrated downregulation of several catabolic enzymes in 8-month-old offspring of NR ewes. These data demonstrate that the early to mid-gestation period is important for skeletal muscle development. Impaired muscle development during this stage of gestation affects the number and composition of fibres in offspring which may lead to long-term physiological consequences, including predisposition to obesity and diabetes. PMID:16763001

  2. Maternal protein restriction induces alterations in hepatic tumor necrosis factor-α/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring

    PubMed Central

    Liu, Xiaomei; Qi, Ying; Tian, Baoling; Chen, Dong; Gao, Hong; Xi, Chunyan; Xing, Yanlin; Yuan, Zhengwei

    2014-01-01

    It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-α (TNF-α)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7α-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-α expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4α and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-α/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life. PMID:25120278

  3. Subcortical band heterotopia in rat offspring following maternal hypothyroxinaemia: structural and functional characteristics.

    PubMed

    Gilbert, M E; Ramos, R L; McCloskey, D P; Goodman, J H

    2014-08-01

    Thyroid hormones (TH) play crucial roles in brain maturation and are important for neuronal migration and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported the presence of SBH in a rodent model of low level hypothyroidism induced by maternal exposure to the goitrogen, propylthiouracil (PTU). In the present study, we report the dose-response characteristics of this developmental malformation and the connectivity of heterotopic neurones with other brain regions, as well as their functionality. Pregnant rats were exposed to varying concentrations of PTU through the drinking water (0-10 p.p.m.) beginning on gestational day 6 to produce graded levels of TH insufficiency. Dose-dependent increases in the volume of the SBH present in the corpus callosum were documented in the adult offspring, with a clear presence at concentrations of PTU that resulted in minor (< 15%) reductions in maternal serum thyroxine as measured when pups were weaned. SBH contain neurones, oligodendrocytes, astrocytes and microglia. Monoaminergic and cholinergic processes were prevalent and many of the axons were myelinated. Anatomical connectivity of SBH neurones to cortical neurones and the synaptic functionality of these anatomical connections was verified by ex vivo field potential recordings. SBH persisted in adult offspring despite a return to euthyroid status on termination of exposure and these offspring displayed an increased sensitivity to seizures. Features of this model are attractive with respect to the investigation of the molecular mechanisms of cortical development, the effectiveness of therapeutic intervention in hypothyroxinaemia during pregnancy and the impact of the very modest TH imbalance that accompanies exposure to environmental contaminants. PMID:24889016

  4. In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

    PubMed Central

    Curran, Christine P.; Genter, Mary Beth; Patel, Krishna V.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on

  5. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice

    PubMed Central

    Hokke, Stacey; Puelles, Victor G.; Armitage, James A.; Fong, Karen; Bertram, John F.; Cullen-McEwen, Luise A.

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20–25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  6. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice.

    PubMed

    Hokke, Stacey; Puelles, Victor G; Armitage, James A; Fong, Karen; Bertram, John F; Cullen-McEwen, Luise A

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20-25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  7. Psychiatric Disorders in Preschool Offspring of Parents with Bipolar Disorder

    PubMed Central

    Birmaher, Boris; Axelson, David; Goldstein, Benjamin; Monk, Kelly; Kalas, Catherine; Obreja, Mihaela; Hickey, Mary Beth; Iyengar, Satish; Brent, David; Shamseddeen, Wael; Diler, Rasim; Kupfer, David

    2010-01-01

    Objective To evaluate lifetime prevalence and specificity of DSM-IV psychiatric disorders and severity of depressive and manic symptoms at intake in preschool offspring of parents with Disorder I–II. Methods 121 offspring ages 2–5 years old of 83 parents with Bipolar Disorder and 102 offspring of 65 demographically matched control parents (29 with non-Bipolar psychiatric disorders and 36 without any lifetime psychopathology) were recruited. Parents with Bipolar Disorder were recruited through advertisement and adult outpatient clinics and control parents were ascertained at random from the community. Subjects were evaluated with standardized instruments. All staff were blind to parental diagnoses. Results After adjusting for within-family correlations and both biological parents’ non-Bipolar psychopathology, compared to the offspring of the control parents, offspring of parents with Bipolar Disorder, particularly those older than 4 years old, showed an 8-fold increased life-time prevalence of Attention Deficit Hyperactive Disorder (ADHD) and significantly higher rates of ≥ 2 psychiatric disorders. While only 3 offspring of parents with Bipolar Disorder had mood disorders, offspring of parents with Bipolar Disorder, especially those with ADHD and Oppositional-Defiant Disorder, had significantly more severe current manic and depressive symptomatology than the offspring of the controls. Conclusions Preschool offspring of parents with Bipolar Disorder are at increased risk for ADHD and demonstrate increased subthreshold manic and depressive symptomatology. Longitudinal follow-up is warranted to evaluate whether these children are at high-risk to develop mood and other psychiatric disorders. PMID:20080982

  8. Food Safety for Pregnant and Breastfeeding Women

    MedlinePlus

    ... Waste Food Safety Newsroom Dietary Guidelines Communicator’s Guide Food Safety You are here Home / Audience / Adults / Moms/ ... and raw sprouts. Do not eat these foods. Food safety advice when you are pregnant Follow the ...

  9. Health & Nutrition Information for Pregnant & Breastfeeding Women

    MedlinePlus

    ... Home / Audience / Adults Pregnancy & Breastfeeding Print Share Health & Nutrition Information When you are pregnant or breastfeeding, you ... Story Last Updated: Feb 2, 2016 RESOURCES FOR NUTRITION AND HEALTH MYPLATE What Is MyPlate? Fruits Vegetables ...

  10. An evaluation of the teratogenic potential of protracted exposure of pregnant rats to 2450-MHz microwave radiation. II. Postnatal psychophysiologic analysis.

    PubMed

    Jensh, R P; Vogel, W H; Brent, R L

    1983-01-01

    The objective of this study was to determine whether protracted prenatal exposure of rats to 2450-MHz microwave radiation at a power density level of 20 mW/cm2 would significantly alter postnatal growth and psychophysiologic development. Of 75 pregnant rats, 12 were exposed to microwave radiation, 4 sham-irradiated, and 59 served as environmental control animals. Forty-five females were allowed to deliver their offspring. The neonates were examined and weighed on d 3 and weekly thereafter until 87 d of age. Neonatal reflex tests were initiated as early as d 3 (surface righting, air righting, auditory startle, visual placing). One physiologic parameter, eye opening, was also observed. Mothers were rebred 10 d after weaning and a morphologic evaluation was completed on the second litter. Behavioral tests were begun at 60 d of age and included water T-maze, conditioned avoidance response, open field, activity wheel, forelimb hanging, and swimming. At 90 d of age offspring were bred within and across groups, and a morphologic teratologic analyses was completed on the offspring. Representative tissue samples were collected and organ weights recorded for the brain, liver, kidneys, and gonads of all animals. Analyses of the data indicated that there were no significant malformations or significant alterations in the neonatal physiologic or reflex test results, body/organ weight ratios, or breeding results in the adult offspring. There were no significant alterations in five of the six adult behavioral tests. There were significant differences in activity among the irradiated and control offspring between the sexes, the irradiated offspring being more active. These results are indicative of possible radiation-induced behavioral alterations. Further studies are needed to explore the possibility of microwave radiation-related alterations in animal behavior. PMID:6827624

  11. Comparison of the effects of fetal hypothyroidism on glucose tolerance in male and female rat offspring.

    PubMed

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Zahediasl, Saleh; Ghasemi, Asghar

    2015-03-01

    Thyroid hormones are vital for survival of mammalian species and play critical roles in growth, development, and metabolism. Both fetal hypothyroidism and sex can affect carbohydrate metabolism during adult life. This study aims to assess carbohydrate metabolism in male and female offspring born from mothers who were hypothyroid during pregnancy. Pregnant rats were divided into two groups; the controls consumed water and the hypothyroid group received water containing 0.025 % 6-propyl-2-thiouracial throughout gestation. The intravenous glucose tolerance test (0.5 g/kg glucose) was carried out in 3-month-old offspring. Findings showed that compared to controls, male fetal hypothyroid rats during adulthood had glucose intolerance (area under the curve: 446.4 ± 9.7 vs. 486.4 ± 8.8, p < 0.01 in control and fetal hypothyroid groups, respectively) whereas females had improved glucose tolerance (478.1 ± 7.0 vs. 455.9 ± 8.5, p < 0.01). In conclusion, sex could modulate the effects of fetal hypothyroidism on glucose tolerance in rats. PMID:25649149

  12. Long term effects of maternal protein restriction on postnatal lung alveoli development of rat offspring.

    PubMed

    Farid, S A; Mahmoud, O M; Salem, N A; Abdel-Alrahman, G; Hafez, G A

    2015-01-01

    Poor nutrition of women during pregnancy causes reduction in foetal growth and can adversely affect the development of the foetal lungs. The purpose of the present study was to assess the effects of maternal protein restriction on the postnatal lung development in neonatal period, and on lung structure in adult rat offspring. Female virgin Sprague-Dawley albino rats (more than 200 g) were used. One male rat was introduced into a cage with one female for matting. Once the pregnancy was confirmed, pregnant rats were divided into two main groups; each consists of 6 female as follow: 1 - normally nourished group; 2 - protein deficient group. After delivery, offspring were subdivided into three groups: 1 day after delivery, 2 weeks and 2 months postnatal. Rat body and lung weight were recorded and ratio of lung weight to body weight was assessed. Total plasma protein and serum albumin were assessed for all groups. Lung tissue stained with H&E for histological and morphometric analysis. Immunohistochemistry was performed to evaluate the number of cells positive for pulmonary surfactant protein A. Our results showed that protein restriction interfere with neonatal and postnatal lung development resulting in morphological and morphometric changes of normal lung development. We concluded that protein deficiency lead to developmental retardation of lung. PMID:26620509

  13. Vaccinations for Pregnant Women

    PubMed Central

    Swamy, Geeta K.; Heine, R. Phillips

    2014-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician–gynecologists are well-suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease–related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and infant benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and provider resources. PMID:25560127

  14. Vaccinations for pregnant women.

    PubMed

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources. PMID:25560127

  15. Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats

    PubMed Central

    Bae, Soochan; Gilbert, Raymond D; Ducsay, Charles A; Zhang, Lubo

    2005-01-01

    The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia–reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg−1) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKCɛ and phospho-PKCɛ levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKCɛ gene expression in the male heart may play an important role. PMID:15677681

  16. Prenatal Polycyclic Aromatic Hydrocarbon, Adiposity, Peroxisome Proliferator-Activated Receptor (PPAR) γ Methylation in Offspring, Grand-Offspring Mice

    PubMed Central

    Yan, Zhonghai; Zhang, Hanjie; Maher, Christina; Arteaga-Solis, Emilio; Champagne, Frances A.; Wu, Licheng; McDonald, Jacob D.; Yan, Beizhan; Schwartz, Gary J.; Miller, Rachel L.

    2014-01-01

    Rationale Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH) have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear. Objectives We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected. Materials and Methods Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND) 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding proteins (C/EBP) α, cyclooxygenase (Cox)-2, fatty acid synthase (FAS) and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue. Findings Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice. Conclusions Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny. PMID:25347678

  17. Reversal of glucose intolerance in rat offspring exposed to ethanol before birth through reduction of nuclear skeletal muscle HDAC expression by the bile acid TUDCA

    PubMed Central

    Yao, Xing‐Hai; Nguyen, Khanh H.; Nyomba, B. L. Grégoire

    2014-01-01

    Abstract Prenatal ethanol exposure causes cellular stress, insulin resistance, and glucose intolerance in adult offspring, with increased gluconeogenesis and reduced muscle glucose transporter‐4 (glut4) expression. Impaired insulin activation of Akt and nuclear translocation of histone deacetylases (HDACs) in the liver partly explain increased gluconeogenesis. The mechanism for the reduced glut4 is unknown. Pregnant rats were gavaged with ethanol over the last week of gestation and adult female offspring were studied. Some ethanol exposed offspring was treated with tauroursodeoxycholic acid (TUDCA) for 3 weeks. All these rats underwent intraperitoneal glucose tolerance and insulin tolerance tests. The expression of glut4, HDACs, and markers of endoplasmic reticulum (ER) unfolded protein response (XBP1, CHOP, ATF6) was examined in the gastrocnemius muscle fractions, and in C2C12 muscle cells cultured with ethanol, TUDCA, and HDAC inhibitors. Non‐TUDCA‐treated rats exposed to prenatal ethanol were insulin resistant and glucose intolerant with reduced muscle glut4 expression, increased ER marker expression, and increased nuclear HDACs, whereas TUDCA‐treated rats had normal insulin sensitivity and glucose tolerance with normal glut4 expression, ER marker expression, and HDAC levels. In C2C12 cells, ethanol reduced glut4 expression, but increased ER makers. While TUDCA restored glut4 and ER markers to control levels and HDAC inhibition rescued glut4 expression, HDAC inhibition had no effect on ER markers. The increase in nuclear HDAC levels consequent to prenatal ethanol exposure reduces glut4 expression in adult rat offspring, and this HDAC effect is independent of ER unfolded protein response. HDAC inhibition by TUDCA restores glut4 expression, with improvement in insulin sensitivity and glucose tolerance. PMID:25538147

  18. Cross-sectional association of dietary patterns with insulin-resistant phenotypes among adults without diabetes in the Framingham Offspring Study.

    PubMed

    Liu, Enju; McKeown, Nicola M; Newby, P K; Meigs, James B; Vasan, Ramachandran S; Quatromoni, Paula A; D'Agostino, Ralph B; Jacques, Paul F

    2009-08-01

    Cluster analysis is a valuable tool for exploring the health consequences of consuming different dietary patterns. We used this approach to examine the cross-sectional relationship between dietary patterns and insulin-resistant phenotypes, including waist circumference, BMI, fasting insulin, 2 h post-challenge insulin, insulin sensitivity index (ISI0,120), HDL-cholesterol, TAG and blood pressure, using data from the fifth examination cycle of the Framingham Offspring Study. Among 2875 participants without diabetes, we identified four dietary patterns based on the predominant sources of energy: 'Fruits, Reduced Fat Dairy and Whole Grains', 'Refined Grains and Sweets', 'Beer' and 'Soda'. After adjusting for multiple comparisons and potential confounders, compared with the 'Fruits, Reduced Fat Dairy and Whole Grains' pattern, the 'Refined Grains and Sweets' pattern had significantly higher mean waist circumference (92.4 v. 90.5 cm; P = 0.008) and BMI (27.3 v. 26.6 kg/m2; P = 0.02); the 'Soda' pattern had significantly higher mean fasting insulin concentration (31.3 v. 28.0 microU/ml; P < or = 0.001); the 'Beer' pattern had significantly higher mean HDL-cholesterol concentration (1.46 v. 1.31 mmol/l; P < 0.001). No associations were observed between dietary patterns and ISI0,120, TAG, and systolic or diastolic blood pressure. Our findings suggest that consumption of a diet rich in fruits, vegetables, whole grains and reduced-fat dairy protects against insulin-resistant phenotypes and displacing these healthy choices with refined grains, high-fat dairy, sweet baked foods, candy and sugar-sweetened soda may promote insulin-resistant phenotypes. PMID:19216828

  19. Dose-dependent effects of perinatal hypothyroidism on postnatal testicular development in rat offspring.

    PubMed

    Kobayashi, Kenichi; Kubota, Hisayo; Hojo, Rieko; Miyagawa, Muneyuki

    2014-01-01

    The role of thyroid hormones in gonad development remains incompletely understood. We examined the dose-related effects of perinatal hypothyroidism induced by a reversible goitrogen, 6-propyl-2-thiouracil (PTU), on reproductive development in male rat offspring. Timed-pregnant Sprague-Dawley rats were orally administered PTU (0, 0.5, 1.0, or 2.0 mg/kg/day) by gavage from gestational day 15 through postnatal day 20. We observed a significant dose-dependent decrease in body weight in offspring with PTU exposure up to 13 weeks of age, but body weight became comparable among groups by 26 weeks of age. Testicular weight tended to be lower up to 7 weeks but was higher after 13 weeks of age. Epididymis weight was not different among the groups at any age. Plasma concentrations of thyroxine and triiodothyronine in the PTU groups were significantly lower at 3 weeks of age but recovered to normal levels by 26 weeks of age. No dose-related trend in plasma testosterone concentrations was found. Seminiferous tubules were larger at 13 and 26 weeks of age with PTU exposure. The number of Sertoli cells was significantly higher from 3 through 26 weeks of age. The number of Leydig cells was significantly lower up to 7 weeks of age but was comparable among groups from 13 weeks of age onwards. Thus, transient gestational and lactational thyroid hormone suppression induced small testes in early life but led to paradoxical dose-dependent testicular enlargement in adults as indicated partly by larger seminiferous tubules with numerous Sertoli cells in male rat offspring. PMID:25392277

  20. Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring

    PubMed Central

    Murugan, Sengottuvelan; Zhang, Changqing; Mojtahedzadeh, Sepideh; Sarkar, Dipak K.

    2013-01-01

    Background Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined if any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol exposed male rats during the adult period. Methods Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed), pair-fed with isocaloric liquid diet (pair-fed), or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostate of these animals were processed for determination of biochemical changes and histopathologies. Results Prostates of non-carcinogen treated animals which were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatally alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia primarily in the ventral prostate, whereas control animals showed only low-grade prostatic intraepithelial neoplasia. Prenatally ethanol-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. Conclusions These results suggest for the first time that prenatal ethanol exposures induces histophysiological changes in the prostate as well as

  1. Do Parental Stressors and Avoidance Coping Mediate between Parental Depression and Offspring Depression? A 23-Year Follow-Up

    ERIC Educational Resources Information Center

    Timko, Christine; Cronkite, Ruth C.; Moos, Rudolf H.

    2010-01-01

    We examined whether parents' stressors and avoidance coping when offspring were children helped to explain associations between parent depression at baseline and offspring's avoidance coping and depression in adulthood. Self-report data were collected at baseline and 1 year from parents (N = 326) and at 23 years from adult offspring (N = 326).…

  2. Maternal and developmental immune challenges alter behavior and learning ability of offspring

    PubMed Central

    Grindstaff, Jennifer L.; Hunsaker, Veronica R.; Cox, Shelby N.

    2012-01-01

    Stimulation of the offspring immune response during development is known to influence growth and behavioral phenotype. However, the potential for maternal antibodies to block the behavioral effects of immune activation during the neonatal period has not been assessed. We challenged female zebra finches (Taeniopygia guttata) prior to egg laying and then challenged offspring during the nestling and juvenile periods with one of two antigens (keyhole limpet hemocyanin (KLH) or lipopolysaccharide (LPS)). We then tested the effects of maternal and neonatal immune challenges on offspring growth rates and neophobia and learning ability of offspring during adulthood. Neonatal immune challenge depressed growth rates. Neophobia of adult offspring was influenced by a combination of maternal treatment, offspring treatment, and offspring sex. Males challenged with LPS during the nestling and juvenile periods had reduced learning performance in a novel foraging task; however, female learning was not impacted. Offspring challenged with the same antigen as mothers exhibited similar growth suppression and behavioral changes as offspring challenged with a novel antigen. Thus, developmental immune challenges have long-term effects on the growth and behavioral phenotype of offspring. We found limited evidence that matching of maternal and offspring challenges reduces the effects of immune challenge in the altricial zebra finch. This may be a result of rapid catabolism of maternal antibodies in altricial birds. Our results emphasize the need to address sex differences in the long-term effects of developmental immune challenge and suggest neonatal immune activation may be one proximate mechanism underlying differences in adult behavior. PMID:22522078

  3. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    SciTech Connect

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L. . E-mail: leonguo@ha.mc.ntu.edu.tw

    2007-05-15

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.

  4. Maternal sleep deprivation inhibits hippocampal neurogenesis associated with inflammatory response in young offspring rats.

    PubMed

    Zhao, Qiuying; Peng, Cheng; Wu, Xiaohui; Chen, Yubo; Wang, Cheng; You, Zili

    2014-08-01

    Although sleep complaints are very common among pregnant women, the potential adverse effects of sleep disturbance on the offspring are not well studied. Growing evidence suggests that maternal stress can induce an inflammatory environment on the fetal development. But people are not sure about the consequences of prenatal stress such as the inflammatory responses induced by maternal sleep deprivation (MSD). In the present study, we investigated the effects of MSD on long-term behavioral and cognitive consequences in offspring and its underlying inflammatory response pathway. The pregnant Wistar rats received prolonged sleep deprivation (72h) on gestational day (GD) 4, 9, and 18, respectively. The post-natal day (PND) 21 offspring showed impaired hippocampus-dependent spatial learning and memory in the Morris Water Maze task and anhedonia in sucrose preference experiment. Quantification of BrdU(+) and DCX(+) cells revealed a significant decrease in hippocampus neurogenesis in prepuberty offspring, especially for the late MSD (GD 18) group. Real-time RT-PCR showed that after MSD, the expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) increased in the hippocampus of offspring on PND 1, 7, 14 and 21, whereas anti-inflammatory cytokine IL-10 reduced at the same time. Immunofluorescence found that the cells of activated microglia were higher in the brains of MSD offspring. Taken together, these results suggested that the MSD-induced inflammatory response is an important factor for neurogenesis impairment and neurobehavioral outcomes in prepuberty offspring. PMID:24769004

  5. Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

    PubMed

    Dorce, Ana Leticia Coronado; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2010-01-01

    The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner. PMID:19945531

  6. Maternal immune activation increases seizure susceptibility in juvenile rat offspring.

    PubMed

    Yin, Ping; Zhang, Xin-Ting; Li, Jun; Yu, Lin; Wang, Ji-Wen; Lei, Ge-Fei; Sun, Ruo-Peng; Li, Bao-Min

    2015-06-01

    Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia. PMID:25982885

  7. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The proportion of obese women who become pregnant continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are matern...

  8. Maternal Exposure to Low Levels of Corticosterone during Lactation Protects against Experimental Inflammatory Colitis-Induced Damage in Adult Rat Offspring

    PubMed Central

    Petrella, Carla; Giuli, Chiara; Agostini, Simona; Bacquie, Valérie; Zinni, Manuela; Theodorou, Vassilia; Broccardo, Maria; Casolini, Paola; Improta, Giovanna

    2014-01-01

    Opposing emotional events (negative/trauma or positive/maternal care) during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a “positive” experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT) (0.2 mg/ml) during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid) was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake) and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R). All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also better adapted

  9. The schooling of offspring and the survival of parents.

    PubMed

    Friedman, Esther M; Mare, Robert D

    2014-08-01

    Contemporary stratification research on developed societies usually views the intergenerational transmission of educational advantage as a one-way effect from parent to child. However, parents' investment in their offspring's schooling may yield significant returns for parents themselves in later life. For instance, well-educated offspring have greater knowledge of health and technology to share with their parents and more financial means to provide for them than do their less-educated counterparts. We use data from the 1992-2006 Health and Retirement Study (HRS) to examine whether adult offspring's educational attainments are associated with parents' survival in the United States. We show that adult offspring's educational attainments have independent effects on their parents' mortality, even after controlling for parents' own socioeconomic resources. This relationship is more pronounced for deaths that are linked to behavioral factors: most notably, chronic lower respiratory disease and lung cancer. Furthermore, at least part of the association between offspring's schooling and parents' survival may be explained by parents' health behaviors, including smoking and physical activity. These findings suggest that one way to influence the health of the elderly is through their offspring. To harness the full value of schooling for health, then, a family and multigenerational perspective is needed. PMID:24917296

  10. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    PubMed Central

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders. PMID:25834439

  11. Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

  12. GESTATIONAL EXPOSURE TO NONYLPHENOL CAUSES PRECOCIOUS MAMMARY GLAND DEVELOPMENT IN FEMALE RAT OFFSPRING

    EPA Science Inventory

    This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on ge...

  13. Pubertal Timing and Early Sexual Intercourse in the Offspring of Teenage Mothers

    ERIC Educational Resources Information Center

    De Genna, Natacha M.; Larkby, Cynthia; Cornelius, Marie D.

    2011-01-01

    Early puberty is associated with stressful family environments, early sexual intercourse, and teenage pregnancy. We examined pubertal timing and sexual debut among the 14-year-old offspring of teenage mothers. Mothers (71% Black, 29% White) were recruited as pregnant teenagers (12-18 years old). Data were collected during pregnancy and when…

  14. Prenatal Activation of Toll-Like Receptor-4 Dampens Adult Hippocampal Neurogenesis in An IL-6 Dependent Manner

    PubMed Central

    Mouihate, Abdeslam

    2016-01-01

    Prenatal immune challenge has been associated with alteration in brain development and plasticity that last into adulthood. We have previously shown that prenatal activation of toll-like receptor 4 by lipopolysaccharide (LPS) induces IL-6-dependent STAT-3 signaling pathway in the fetal brain. Whether this IL-6-dependent activation of fetal brain results in long lasting impact in brain plasticity is still unknown. Furthermore, it has been shown that prenatal LPS heightens the hypothalamic–pituitary–adrenal (HPA) response in adulthood. In the present study we tested whether LPS administration during pregnancy affects neurogenesis in adult male offspring. Because corticosterone, the end-product of HPA axis activity in rats, alters neurogenesis we tested whether this enhanced HPA axis responsiveness in adult male offspring played a role in the long lasting impact of LPS on neurogenesis during adulthood. Pregnant rats were given either LPS, or LPS and an IL-6 neutralizing antibody (IL-6Ab). The newly born neurons were monitored in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus of adult male offspring by monitoring doublecortin and T-box brain protein-2 expression: two well-established markers of newly born neurons. Prenatal LPS decreased the number of newly born neurons in the DG, but not in the SVZ of adult offspring. This decreased number of newly born neurons in the DG was absent when IL-6Ab was co-injected with LPS during pregnancy. Furthermore, administration of a corticosterone receptor blocker, RU-486, to adult offspring blunted the prenatal LPS induced decrease in newly born neurons in the DG. These data suggest that maternally triggered IL-6 plays a crucial role in the long lasting impact of LPS on adult neurogenesis. PMID:27445700

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

    SciTech Connect

    Axelstad, Marta; Boberg, Julie; Hougaard, Karin Sorig; Christiansen, Sofie; Jacobsen, Pernille Rosenskjold; Mandrup, Karen Riiber; Nellemann, Christine; Lund, Soren Peter; Hass, Ulla

    2011-02-01

    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. On 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 the

  16. Prenatal exposure to LPS leads to long-lasting physiological consequences in male offspring.

    PubMed

    Asiaei, Masoud; Solati, Jalal; Salari, Ali-Akbar

    2011-12-01

    Growing evidence suggests that early life events are critical determinants for disorders later in life. According to a comprehensive number of epidemiological/animal studies, exposure to lipopolysaccharide, causes alteration in pro-inflammatory cytokine levels, hypothalamic-pituitary-adrenal functioning and the hormonal system which may contribute to behavioral and neurological injuries. In this study we investigated the effects of lipopolysaccharide administration on physiological parameters in pregnant dams and their male offspring aged 9 weeks. In gestational Day 10, pregnant mice were injected intrapritoneally with Salmonella enterica lipopolysaccharide to model prenatal exposure to infection. The following results were obtained for offspring from dams stressed during pregnancy: (a) reduced anxiety-related behavior in the elevated plus maze; (b) reduced food and water intake; (c) reduced body weight from birth up to postnatal Day 40. The observed data provide experimental evidence showing that prenatal stress can have complex and long-lasting physiological/behavioral consequences in offspring. PMID:21630247

  17. Rift Valley Fever Virus Vaccine Lacking the NSs and NSm Genes Is Safe, Nonteratogenic, and Confers Protection from Viremia, Pyrexia, and Abortion following Challenge in Adult and Pregnant Sheep ▿

    PubMed Central

    Bird, Brian H.; Maartens, Louis H.; Campbell, Shelley; Erasmus, Baltus J.; Erickson, Bobbie R.; Dodd, Kimberly A.; Spiropoulou, Christina F.; Cannon, Deborah; Drew, Clifton P.; Knust, Barbara; McElroy, Anita K.; Khristova, Marina L.; Albariño, César G.; Nichol, Stuart T.

    2011-01-01

    Rift Valley fever virus (RVFV) is a mosquito-borne human and veterinary pathogen causing large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Safe and effective vaccines are critically needed, especially those that can be used in a targeted one-health approach to prevent both livestock and human disease. We report here on the safety, immunogenicity, and efficacy of the ΔNSs-ΔNSm recombinant RVFV (rRVFV) vaccine (which lacks the NSs and NSm virulence factors) in a total of 41 sheep, including 29 timed-pregnant ewes. This vaccine was proven safe and immunogenic for adult animals at doses ranging from 1.0 × 103 to 1.0 × 105 PFU administered subcutaneously (s.c.). Pregnant animals were vaccinated with 1.0 × 104 PFU s.c. at day 42 of gestation, when fetal sensitivity to RVFV vaccine-induced teratogenesis is highest. No febrile reactions, clinical illness, or pregnancy loss was observed following vaccination. Vaccination resulted in a rapid increase in anti-RVFV IgM (day 4) and IgG (day 7) titers. No seroconversion occurred in cohoused control animals. A subset of 20 ewes progressed to full-term delivery after vaccination. All lambs were born without musculoskeletal, neurological, or histological birth defects. Vaccine efficacy was assessed in 9 pregnant animals challenged at day 122 of gestation with virulent RVFV (1.0 × 106 PFU intravenously). Following challenge, 100% (9/9) of the animals were protected, progressed to full term, and delivered healthy lambs. As expected, all 3 sham-vaccinated controls experienced viremia, fetal death, and abortion postchallenge. These results demonstrate that the ΔNSs-ΔNSm rRVFV vaccine is safe and nonteratogenic and confers high-level protection in sheep. PMID:21976656

  18. Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization.

    PubMed

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez-Garcia, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D'Mello, Anil P

    2015-04-01

    We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty-acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low-protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity, suggesting increased fatty-acid transport into the mitochondrial matrix. However, medium-chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty-acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low-protein offspring is likely due to alterations in liver fatty-acid transport or triglyceride biosynthesis. PMID:25641378

  19. Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization

    PubMed Central

    Qasem, Rani J.; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D’mello, Anil P.

    2015-01-01

    We have previously demonstrated that protein restriction throughout gestation and lactation reduced liver triglyceride content in adult rat offspring. The mechanism(s) mediating the decrease in liver triglyceride content are not understood. The objective of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and sacrificed on day 65. Liver triglyceride content was reduced in male, but not female, low protein offspring both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity suggesting increased fatty acid transport into the mitochondrial matrix. However, medium chain acyl CoA dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-hydroxybutyrate were similar between low protein and control offspring indicating a lack of change in fatty acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein were similar between low protein and control offspring. Since enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low protein offspring is likely due to alterations in liver fatty acid transport or triglyceride biosynthesis. PMID:25641378

  20. Swimming of pregnant rats at different water temperatures.

    PubMed

    Osorio, R A L; Silveira, V L F; Maldjian, S; Morales, A; Christofani, J S; Russo, A K; Silva, A C; Piçarro, I C

    2003-08-01

    We studied the chronic effect of exercise during water immersion, associated with thermal stress (water temperature at 22, 35 and 40 degrees C) at an intensity of 80% of maximal work load supported in pregnant rats (P) and non-pregnant female rats (NP). P and NP were subdivided into three subgroups according to water temperature during exercise (P22 and NP22; P35 and NP35; P40 and NP40). The animals were submitted to daily swimming sessions of 10-15 min, for 19 days of pregnancy (P) or experimental conditions (NP). Plasma concentration of triglycerides, cholesterol, glucose, total protein, albumin and corticosterone were determined 24 h after the last exercise session. Weight gain and rectal temperature pre- and post-swimming session were also determined. The offspring were examined just after caesarian section on the 20th day of pregnancy to check weight, length and litter size. Pregnant rats showed an increase of triglycerides, reduction of glycemia, total protein and albumin and cholesterol (at 35 degrees C) when compared to non-pregnant animals. Such effects probably lead to an adequate delivery of substrate to the fetus and prepare the mother for lactation. Daily thermal stress did not modify metabolic responses to exercise in pregnant rats. Results also show a deleterious effect on offspring when the mother is exposed daily to extreme temperatures during swimming. These results suggest that water temperature (cold and hot) in swimming have to be considered to avoid damage in fetal development. PMID:12890550

  1. Impaired development of female mouse offspring maternally exposed to simazine.

    PubMed

    Park, Seeun; Kim, Sarang; Jin, Hong; Lee, Kangseok; Bae, Jeehyeon

    2014-11-01

    Simazine is a suspected endocrine disruptor and the second most commonly detected pesticide in surface and groundwater worldwide. We evaluated the toxicity of simazine in female mouse offspring with in utero and lactational exposure to the agent. Pregnant mice were exposed to environmentally relevant doses (from 5 to 500μg/kg) of simazine via oral administration, and their female offspring were then analyzed. The female offspring showed shortened anogenital distance and decreased whole body, ovarian, and uterine weights. Their ovaries showed increased apoptotic granulosa cells. In addition, expression of critical genes involved in regulation of cellular apoptosis and proliferation was significantly downregulated in the ovaries of simazine-exposed mice. Moreover, in vitro exposure of human granulosa cell-derived KGN cells to simazine (0.003-1nM) resulted in decreased viability and proliferation. Thus, the present study demonstrates that maternal exposure to low doses of simazine impairs normal development of female offspring via disturbance of cellular apoptosis and proliferation. PMID:25461544

  2. Effects of low doses of alcohol on delta-9-tetrahydrocannabinol's effects in pregnant rats

    SciTech Connect

    Abel, E.L.; Subramanian, M.G. )

    1990-01-01

    Pregnant rats were intubated with 50 mg/kg of delta-9-tetrahydrocannabinol (THC) or with THC plus alcohol to determine if a low dose of alcohol would significantly increase blood levels of THC. On the basis of this study, a second study was conducted in which pregnant rats were intubated with THC plus alcohol from gestation day six to parturition. THC reduced birth weights but did not significantly affect litter size or passive avoidance learning. Alcohol did not have a significant effect on offspring birth weight nor did it interact with THC to affect offspring.

  3. Elevated cortisol in healthy female adolescent offspring of mothers with posttraumatic stress disorder.

    PubMed

    Liu, Keke; Ruggero, Camilo J; Goldstein, Brandon; Klein, Daniel N; Perlman, Greg; Broderick, Joan; Kotov, Roman

    2016-05-01

    Offspring with maternal PTSD are at increased risk of developing PTSD themselves. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis may play a role and have been noted in offspring, although evidence is mostly from adult offspring with PTSD symptoms themselves. The present study of adolescent girls (N=472) and their mothers (n=18 with lifetime PTSD versus n=454 with no PTSD) sought to determine whether healthy, non-affected offspring of mothers with PTSD would exhibit altered HPA axis function. Saliva samples were collected from the adolescent girls at waking, 30min after waking, and 8 pm on 3 consecutive days. Offspring whose mothers were diagnosed with PTSD demonstrated higher cortisol awakening response (CAR; Cohen's d=0.58) and greater total cortisol output (Cohen's d=0.62). In this preliminary study, higher cortisol levels during adolescence among offspring of mothers with PTSD may index a vulnerability in these at-risk youth. PMID:27088877

  4. Congenital anomalies in the offspring of rats after exposure of the testis to an electrostatic field.

    PubMed

    Soeradi, O; Tadjudin, M K

    1986-04-01

    The effect of electrostatic field treatment of the testis on the offspring of male rats was investigated. The results showed that treatment ranging from 1 to 7 kV caused reduced fertility, but no deaths occurred among the treated animals during the experiment. Observations at 3, 30, 60 and 90 days after exposure showed no recovery of fertility among the treated rats. Treatment with 6 or 7 kV caused congenital anomalies in the offspring, such as micropthalmy, elongation of the foreskin of the penis (praeputium-like), 'rounded face' with omnidirectional hair growth, and narrow pelvis in adult female offspring. The anomalies might be caused by changes to the genetic material in the sperm. The sex ratio of offspring in the experimental groups was not significantly different from normal, suggesting that the number of male and female offspring was unaffected by treatment. The number of offspring with experimentally linked congenital anomalies decreased with time. PMID:3793258

  5. Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans.

    PubMed

    Lee, Hwayoung; Joo, Jaesoon; Nah, Seong-Su; Kim, Jong Woo; Kim, Hyung-Ki; Kwon, Jun-Tack; Lee, Hwa-Young; Kim, Young Ock; Kim, Hak-Jae

    2015-06-01

    Exposure to stress during critical periods of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. In the present study, a repeated-variable stress paradigm was applied to pregnant rats during the last week of gestation, which is analogous to the second trimester of brain development in humans. Behavioral and proteomic analyses were conducted in prenatally-stressed (PNS) adult offspring and non-stressed (NS) adult controls. In the behavioral tests, grooming behavior in the social interaction test, line-crossing behavior in the open field test, and swimming behavior in the forced swimming test were decreased in the PNS group. Western blot analysis and immunohistochemical analysis revealed that the expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population. Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon region) were associated with susceptibility to schizophrenia. The present findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3 in a rat model of prenatal stress may affect subsequent behavioral changes and that polymorphisms of the DPYSL2 gene in humans may be associated with the development of schizophrenia. Taken together with previous studies investigating the association between the DPYSL2 gene and schizophrenia, the present findings may contribute additional evidence regarding developmental theories of the pathophysiology of schizophrenia. PMID:25847191

  6. Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans

    PubMed Central

    LEE, HWAYOUNG; JOO, JAESOON; NAH, SEONG-SU; KIM, JONG WOO; KIM, HYUNG-KI; KWON, JUN-TACK; LEE, HWA-YOUNG; KIM, YOUNG OCK; KIM, HAK-JAE

    2015-01-01

    Exposure to stress during critical periods of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. In the present study, a repeated-variable stress paradigm was applied to pregnant rats during the last week of gestation, which is analogous to the second trimester of brain development in humans. Behavioral and proteomic analyses were conducted in prenatally-stressed (PNS) adult offspring and non-stressed (NS) adult controls. In the behavioral tests, grooming behavior in the social interaction test, line-crossing behavior in the open field test, and swimming behavior in the forced swimming test were decreased in the PNS group. Western blot analysis and immunohistochemical analysis revealed that the expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population. Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon region) were associated with susceptibility to schizophrenia. The present findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3 in a rat model of prenatal stress may affect subsequent behavioral changes and that polymorphisms of the DPYSL2 gene in humans may be associated with the development of schizophrenia. Taken together with previous studies investigating the association between the DPYSL2 gene and schizophrenia, the present findings may contribute additional evidence regarding developmental theories of the pathophysiology of schizophrenia. PMID:25847191

  7. Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment

    PubMed Central

    Plant, Dominic T.; Pariante, Carmine M.; Sharp, Deborah; Pawlby, Susan

    2015-01-01

    Background Studies have shown that maternal depression during pregnancy predicts offspring depression in adolescence. Child maltreatment is also a risk factor for depression. Aims To investigate (a) whether there is an association between offspring exposure to maternal depression in pregnancy and depression in early adulthood, and (b) whether offspring child maltreatment mediates this association. Method Prospectively collected data on maternal clinical depression in pregnancy, offspring child maltreatment and offspring adulthood (18–25 years) DSM-IV depression were analysed in 103 mother–offspring dyads of the South London Child Development Study. Results Adult offspring exposed to maternal depression in pregnancy were 3.4 times more likely to have a DSM-IV depressive disorder, and 2.4 times more likely to have experienced child maltreatment, compared with non-exposed offspring. Path analysis revealed that offspring experience of child maltreatment mediated the association between exposure to maternal depression in pregnancy and depression in adulthood. Conclusions Maternal depression in pregnancy is a key vulnerability factor for offspring depression in early adulthood. PMID:26045352

  8. Maternal Obesity at Conception Programs Obesity in the Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adult life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in the offspring, we have developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via ...

  9. Maternal overweight programs insulin and adiponectin signaling in the offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult-life. Male offspring from OW dams gain greater body weight, fat mass and develop insulin resistance when fed high fat diets (45 percent fat). In this report we identify molecular targets of maternal OW-induced p...

  10. Maternal Obesity at Conception Programs Obesity in the Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adult-life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in the offspring, we have developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via ...

  11. Prenatal LPS-exposure--a neurodevelopmental rat model of schizophrenia--differentially affects cognitive functions, myelination and parvalbumin expression in male and female offspring.

    PubMed

    Wischhof, Lena; Irrsack, Ellen; Osorio, Carmen; Koch, Michael

    2015-03-01

    Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. Gender differences can be seen in various features of the illness and sex steroid hormones (e.g. estrogen) have strongly been implicated in the disease pathology. In the present study, we evaluated sex differences in the effects of prenatal exposure to a bacterial endotoxin (lipopolysaccharide, LPS) in rats. Pregnant dams received LPS-injections (100 μg/kg) at gestational day 15 and 16. The offspring was then tested for prepulse inhibition (PPI), locomotor activity, anxiety-like behavior and object recognition memory at various developmental time points. At postnatal day (PD) 33 and 60, prenatally LPS-exposed rats showed locomotor hyperactivity which was similar in male and female offspring. Moreover, prenatal LPS-treatment caused PPI deficits in pubertal (PD45) and adult (PD90) males while PPI impairments were found only at PD45 in prenatally LPS-treated females. Following prenatal LPS-administration, recognition memory for objects was impaired in both sexes with males being more severely affected. Additionally, we assessed prenatal infection-induced alterations of parvalbumin (Parv) expression and myelin fiber density. Male offspring born to LPS-challenged mothers showed decreased myelination in cortical and limbic brain regions as well as reduced numbers of Parv-expressing cells in the medial prefrontal cortex (mPFC), hippocampus and entorhinal cortex. In contrast, LPS-exposed female rats showed only a modest decrease in myelination and Parv immunoreactivity. Collectively, our data indicate that some of the prenatal immune activation effects are sex dependent and further strengthen the importance of taking into account gender differences in animal models of schizophrenia. PMID:25455585

  12. Maternal Overweight Programs Insulin and Adiponectin Signaling in the Offspring

    PubMed Central

    Shankar, Kartik; Kang, Ping; Harrell, Amanda; Zhong, Ying; Marecki, John C.; Ronis, Martin J. J.; Badger, Thomas M.

    2010-01-01

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr308) and phospho-insulin receptor-β were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-α signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-α-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr172) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal

  13. Paternal fenvalerate exposure influences reproductive functions in the offspring.

    PubMed

    Xia, Dong; Parvizi, Nahid; Zhou, Yuchuan; Xu, Kesi; Jiang, Hui; Li, Rongjie; Hang, Yiqiong; Lu, Yang

    2013-11-01

    Fenvalerate (Fen), a synthetic pyrethroid insecticide, has been shown to have adverse effects on male reproductive system. Thus, the aim of the present study was to elucidate whether these adverse effects are passed from exposed male mice to their offspring. Adult male mice received Fen (10 mg/kg) daily for 30 days and mated with untreated females to produce offspring. Fenvalerate significantly changed the methylation status of angiotensin I-converting enzyme (Ace), forkhead box O3 (Foxo3a), huntingtin-associated protein 1 (Hap1), nuclear receptor subfamily 3 (Nr3c2), promyelocytic leukemia (Pml), and Prostaglandin F2 receptor negative regulator (Ptgfrn) genes in paternal mice sperm genomic DNA. Further, Fen significantly increased sperm abnormalities; serum testosterone and estradiol-17ß level in adult male (F0) and their male offspring (F1). Further, paternal Fen treatment significantly increased the length of estrous cycle, serum estradiol-17ß concentration in estrus, and progesterone levels in diestrus in female offspring (F1). These findings suggest that adverse effects of paternal Fen exposure on reproductive functions can be seen not only in treated males (F0) but also in their offsprings. PMID:23548413

  14. Maternal cypermethrin exposure during the perinatal period impairs testicular development in C57BL male offspring.

    PubMed

    Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Numerous studies have demonstrated that endocrine-disrupting compounds (EDC) are a possible cause of male reproductive organ malfunction and malformation. Cypermethrin (CYP) is a widely used synthetic pyrethroid and a potential EDC. This study aimed to examine the effects of perinatal exposure to low-dose CYP on the development and function of the offspring testes. Pregnant mice were intragastrically administered 0.12 to 12 mg/kg/day CYP from embryonic day 0.5 (E0.5) to weaning (PD21.5, postnatal day 21.5). Maternal exposure to 0.12, 1.2, and 12 mg/kg/day CYP affected the body and organ weight of the offspring. Exposure of CYP led to a dose-dependent decrease in the male-to-female sex ratio. A histopathological analysis revealed a thinner seminiferous epithelium layer at PD21.5, interstitial hyperplasia at PD45.5, and germ cell vacuolization at PD90.5 in the 12 mg/kg/day CYP group. The TUNEL assay results revealed increased germ cell apoptosis in the 12 mg/kg/day CYP group. The serum testosterone (T) level decreased, whereas the estradiol level increased with age in the 1.2 and 12 mg/kg/day CYP groups. The RT-PCR analysis demonstrated decreased expression of T production-related, mitosis-related, and meiosis-related genes in the 1.2 and 12 mg/kg/day CYP groups. The in vitro experimental results demonstrated reduced expression of steroidogenesis genes and decreased T levels. It is concluded that perinatal exposure to low-dose CYP affects testes development and function in adults. PMID:24810582

  15. Maternal Cypermethrin Exposure during the Perinatal Period Impairs Testicular Development in C57BL Male Offspring

    PubMed Central

    Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Numerous studies have demonstrated that endocrine-disrupting compounds (EDC) are a possible cause of male reproductive organ malfunction and malformation. Cypermethrin (CYP) is a widely used synthetic pyrethroid and a potential EDC. This study aimed to examine the effects of perinatal exposure to low-dose CYP on the development and function of the offspring testes. Pregnant mice were intragastrically administered 0.12 to 12 mg/kg/day CYP from embryonic day 0.5 (E0.5) to weaning (PD21.5, postnatal day 21.5). Maternal exposure to 0.12, 1.2, and 12 mg/kg/day CYP affected the body and organ weight of the offspring. Exposure of CYP led to a dose-dependent decrease in the male-to-female sex ratio. A histopathological analysis revealed a thinner seminiferous epithelium layer at PD21.5, interstitial hyperplasia at PD45.5, and germ cell vacuolization at PD90.5 in the 12 mg/kg/day CYP group. The TUNEL assay results revealed increased germ cell apoptosis in the 12 mg/kg/day CYP group. The serum testosterone (T) level decreased, whereas the estradiol level increased with age in the 1.2 and 12 mg/kg/day CYP groups. The RT-PCR analysis demonstrated decreased expression of T production-related, mitosis-related, and meiosis-related genes in the 1.2 and 12 mg/kg/day CYP groups. The in vitro experimental results demonstrated reduced expression of steroidogenesis genes and decreased T levels. It is concluded that perinatal exposure to low-dose CYP affects testes development and function in adults. PMID:24810582

  16. Maternal Early Life Risk Factors for Offspring Birth Weight: Findings from the Add Health Study

    PubMed Central

    Thompson, Elaine; Rue, Tessa; Guo, Yuqing

    2014-01-01

    The aim of this study was to examine the pathways that link mothers’ early life socioeconomic status (SES) and mothers’ experience of childhood maltreatment with birth weight among their later born offspring. Data were drawn from a nationally representative longitudinal survey of school-aged respondents, initially enrolled during adolescence in Wave I (1994–1995) and Wave II (1996) of the National Longitudinal Study of Adolescent Health and followed-up in adulthood in Wave III (2001–2002). Data on offspring birth weight were obtained from nulliparous females (N=1,897) who had given birth between Waves II and III. Analyses used structural equation modeling to examine the extent to which early life maternal risk predicted offspring birth weight, and demonstrated that maternal childhood SES and maternal childhood maltreatment predicted offspring birth weight through several mediated pathways. First, maternal adolescent substance use and prenatal cigarette use partially mediated the association between maternal childhood SES and offspring birth weight. Second, maternal adolescent depressive symptoms and adult SES partially mediated the association between maternal childhood SES and offspring birth weight. Third, adult SES partially mediated the association between maternal childhood SES and offspring birth weight. Fourth, maternal adolescent substance use and prenatal cigarette use partially mediated the association between maternal childhood maltreatment and offspring birth weight. Finally, maternal adolescent depressive symptoms and adult SES partially mediated the association between maternal childhood maltreatment and offspring birth weight. To our knowledge, this is the first study to identify maternal childhood maltreatment as an early life risk factor for offspring birth weight among a nationally representative sample of young women, and to demonstrate the mechanisms that link childhood SES and maltreatment to offspring birth weight. These findings

  17. Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal, family study

    PubMed Central

    MacGregor, Erica K.; Grunebaum, Michael F.; Galfalvy, Hanga C.; Melhem, Nadine; Burke, Ainsley K.; Brent, David A.; Oquendo, Maria A.; Mann, J. John

    2015-01-01

    Objective To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. Method 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992–2008 during a longitudinal family study completed January 31, 2014. Results Parent avoidant attachment predicted offspring suicide attempts at a trend level (p=0.083). Parent anxious attachment did not predict offspring attempts (p=0.961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (p=0.034), and in offspring suicide attempters, was associated with greater intent (p=0.045) and lethality of attempts (p=0.003). Avoidant attachment in parents was associated with offspring impulsivity (p=0.025) and major depressive disorder (p=0.012). Parent avoidant attachment predicted a greater number of suicide attempts (p=0.048) and greater intent in offspring attempters (p=0.003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Conclusion Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parent attachment traits were associated with impulsivity and major depressive disorder in all offspring, and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. PMID:25098943

  18. Pregnant phenotype in aquaporin 8-deficient mice

    PubMed Central

    Sha, Xiao-yan; Xiong, Zheng-fang; Liu, Hui-shu; Zheng, Zheng; Ma, Tong-hui

    2011-01-01

    Aim: Aquaporin 8 (AQP8) is expressed within the female reproductive system but its physiological function reminds to be elucidated. This study investigates the role of AQP8 during pregnancy using AQP8-knockout (AQP8-KO) mice. Methods: Homozygous AQP8-KO mice were mated, and the conception rate was recorded. AQP8-KO pregnant mice or their offspring were divided into 5 subgroups according to fetal gestational day (7, 13, 16, 18 GD) and newborn. Wild type C57 pregnant mice served as the control group. The number of pregnant mice, total embryos and atrophic embryos, as well as fetal weight, placental weight and placental area were recorded for each subgroup. The amount of amniotic fluid in each sac at 13, 16, and 18 GD was calculated. Statistical significance was determined by analysis of variance of factorial design and chi-square tests. Results: Conception rates did not differ significantly between AQP8-KO and wild type mice. AQP8-KO pregnant mice had a significantly higher number of embryos compared to wild type controls. Fetal/neonatal weight was also significantly greater in the AQP8-KO group compared to age-matched wild type controls. The amount of amniotic fluid was greater in AQP8-KO pregnant mice than wild type controls, although the FM/AFA (fetal weight/amniotic fluid amount) did not differ. While AQP8-KO placental weight was significantly larger than wild type controls, there was no evidence of placental pathology in either group. Conclusion: The results suggest that AQP8 deficiency plays an important role in pregnancy outcome. PMID:21602842

  19. Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring.

    PubMed

    Xu, Xin-Jie; Zhang, Hong-Feng; Shou, Xiao-Jing; Li, Jin; Jing, Wei-Long; Zhou, Ying; Qian, Yi; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

    2015-01-01

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent impairment in social communication and social interaction. Recent studies revealed that environmental factors, especially the intrauterine developmental environment, played important roles in the development of ASD. It is hypothesized that maternal hyperandrogenism during pregnancy may increase the susceptibility of the fetus to ASD. In the present study, pregnant rats were treated with a low dose of letrozole (1μg/kg/day) in an attempt to produce a hyperandrogenic intrauterine environment for the developing fetus. Results showed that rat pups prenatally exposed to hyperandrogenic intrauterine environment emitted less number of ultrasonic vocalizations when isolated from their dams and littermates. Additionally, the female rats in the treatment group spent less time in social interaction in adolescence and exhibited impaired heterosexual interaction in adult. Moreover, the duration of social interaction and heterosexual interaction of the female offspring were negatively correlated with maternal serum testosterone levels during pregnancy. These results suggest that prenatal exposure to hyperandrogenic intrauterine environment could induce autistic-like behavior in female rats and maternal hyperandrogenism during pregnancy should be considered as a potential risk factor for the etiology of ASD. PMID:25455866

  20. Intrauterine stress induces bone loss in adult offspring of C3H/HeJ mice having high bone mass phenotype but not C57BL/6J mice with low bone mass phenotype.

    PubMed

    Raygorodskaya, M; Gabet, Y; Shochat, C; Kobyliansky, E; Torchinsky, A; Karasik, D

    2016-06-01

    In this study we examined to what extent and how genetics may modify osteoporosis risk arising due to environmental stresses which act during the antenatal period of life and have the potential to induce bone loss in adulthood. C57Bl/6J (C57) and C3H/HeJ (C3H) mice were used as a model system. The mice were exposed to a single injection of 5-aza-2'-deoxycytidine (5-AZA) on day 10 of pregnancy and the structure and bone mineral density (BMD) of the femur and 3rd lumbar vertebra of 3- and 6-month-old male and female offspring were evaluated by micro-computed tomography (μCT). Besides, we also attempted to evaluate whether 5-AZA affects the expression of some osteogenic genes in the embryonic limb buds. The main observation of this study is that 5-AZA-induced loss of bone quality was registered in 6-mo-old C3H offspring but not in their C57 counterparts. We also observed that C57 and C3H embryos may differ in their response to 5-AZA-induced detrimental stimuli: whereas 5-AZA treated C3H embryos exhibited a decreased expression of Col1a1, C57 embryos exhibit a decreased expression of Sox9. Overall, our study, by thorough characterization of bone homeostasis in 3- and 6-month-old offspring of 5-AZA-exposed C57 and C3H mice, allows hypothesizing that the adaptive response to antenatal insults may be stronger in offspring inherently exhibiting a low bone mass phenotype than in offspring inherently exhibiting a high bone mass phenotype. PMID:27072519

  1. Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring.

    PubMed

    Konycheva, Galina; Dziadek, Marie A; Ferguson, Lynnette R; Krägeloh, Christian U; Coolen, Marcel W; Davison, Michael; Breier, Bernhard H

    2011-10-01

    Two important lines of research have enhanced our understanding of the molecular role of nutrition in influencing behavior. First, exposure to an adverse environment during early life can influence the long-term behavior of the offspring. Second, regulation of the nervous system development and functioning appears to involve epigenetic mechanisms that require a continuous supply of methyl group donors in food. We hypothesized that a maternal diet during pregnancy deficient in methyl donors (MDD) may lead to altered behavior in offspring through permanent changes in hippocampal DNA methylation. We used a rat model of prenatal dietary MDD to test this hypothesis in female offspring as they aged. Prenatal MDD reduced birth weight, litter size, and newborn viability. Aged female offspring of MDD mothers showed increased anxiety and increased learning ability in comparison with control diet group offspring. To explore the role of MDD on epigenetic mechanisms in the brain of adult offspring, we studied expression and methylation of 4 selected genes coding for glucocorticoid receptor, hydroxysteroid dehydrogenase 11 type 2, neuronatin, and reelin proteins in the hippocampus. No major group differences in methylation or expression of the studied genes were detected, except for a significant down-regulation of the reelin gene in the MDD female offspring. The prenatal MDD diet caused intrauterine growth restriction, associated with long-term effects on the behavior of the offspring. However, the observed behavioral differences between the MDD and control diet offspring cannot be explained by epigenetic regulation of the specific genes investigated in this study. PMID:22074804

  2. Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood

    PubMed Central

    Moon, RJ; Harvey, NC; Robinson, SM; Ntani, G; Davies, JH; Inskip, HM; Godfrey, KM; Dennison, EM; Calder, PC; Cooper, C

    2013-01-01

    Context Maternal diet during pregnancy has been linked to offspring adiposity, but it is unclear whether maternal polyunsaturated fatty acid (PUFA) status during pregnancy affects offspring body composition. Objective We investigated the associations between maternal plasma n-3 and n-6 PUFA status at 34 weeks gestation and offspring body composition. Design and setting A prospective UK population-based mother-offspring cohort: the Southampton Women’s Survey (SWS). Participants 12583 non-pregnant women were recruited into the SWS, of which 1987 delivered a baby before 31st December 2003. 293 mother-child pairs had complete measurements of maternal plasma PUFA concentrations in late pregnancy and offspring body composition at ages 4 and 6 years. Main Outcomes Measured Offspring body composition by DXA, yielding fat mass(FM), lean mass(LM), percentage fat mass(%FM) and percentage lean mass(%LM). Results Maternal plasma n-6 PUFA concentration positively predicted offspring fat mass at 4 years (β=0.14 SD/SD, p=0.01) and 6 years (β=0.11 SD/SD, p=0.04), but there was no association with offspring lean mass at either age (β=0.005 SD/SD, p=0.89 & β=0.008 SD/SD, p=0.81, respectively). Maternal plasma n-3 PUFA concentration displayed no associations with offspring fat mass at 4 years (β=0.057 SD/SD, p=0.34) or 6 years (β=0.069 SD/SD, p=0.21). Maternal plasma n-3 PUFA status positively correlated with offspring lean mass on univariate analysis (4yrs β=0.11, p=0.06; 6yrs β=0.14, p=0.02), however this was confounded by a positive association with offspring height. Conclusions This observational study suggests that maternal n-6 PUFA status during pregnancy might influence offspring adiposity in childhood. PMID:23162098

  3. Maternal obesity, lipotoxicity and cardiovascular diseases in offspring.

    PubMed

    Dong, Maolong; Zheng, Qijun; Ford, Stephen P; Nathanielsz, Peter W; Ren, Jun

    2013-02-01

    Maternal obesity has risen dramatically over the past 20 years, by nearly 42% in African-Americans and 29% in Caucasians. Maternal obesity is afflicted with many maternal obstetric complications in the offspring including high blood pressure, obesity, gestational diabetes and increased perinatal morbidity. Maternal nutritional environment plays a rather important role in the programming of the health set-points in the offspring such as glucose and insulin metabolism, energy balance and predisposition to metabolic disorders. In particular, maternal obesity is associated with elevated prevalence of cardiovascular diseases in the offspring. Evidence from human and experimental studies including rodents and nonhuman primates has indicated that maternal obesity or overnutrition programs offspring for an increased risk of adult obesity. Maternal obesity or fat diet exposure predisposes the onset and development of obesity, insulin resistance, cardiac hypertrophy and myocardial contractile anomalies in the offspring. A number of mechanisms including elevated hormones (leptin, insulin), nutrients (fatty acids, triglycerides and glucose) and inflammatory cytokines have been postulated to play a key role in maternal obesity-induced postnatal cardiovascular sequelae. In addition, lipotoxicity (accumulation of lipid metabolites) resulting from maternal obesity is capable of activating a number of stress signaling cascades including pro-inflammatory cytokines and oxidative stress to exacerbate maternal obesity-induced cardiovascular complications later on in adult life. This mini-review summarizes the recent knowledge with regard to the role of lipotoxicity in maternal obesity-induced change in cardiovascular function in the offspring. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". PMID:22982026

  4. Sex roles in nest keeping - how information asymmetry contributes to parent-offspring co-adaptation.

    PubMed

    Lucass, Carsten; Fresneau, Nolwenn; Eens, Marcel; Müller, Wendt

    2016-03-01

    Parental food provisioning and offspring begging influence each other reciprocally. This makes both traits agents and targets of selection, which may ultimately lead to co-adaptation. The latter may reflect co-adapted parent and offspring genotypes or could be due to maternal effects. Maternal effects are in turn likely to facilitate in particular mother-offspring co-adaptation, further emphasized by the possibility that mothers are sometimes found to be more responsive to offspring need. However, parents may not only differ in their sensitivity, but often play different roles in postnatal care. This potentially impinges on the access to information about offspring need. We here manipulated the information on offspring need as perceived by parents by playing back begging calls at a constant frequency in the nest-box of blue tits (Cyanistes caeruleus). We measured the parental response in provisioning to our treatment, paying particular attention to sex differences in parental roles and whether such differences alter the perception of the intensity of our manipulation. This enabled us to investigate whether an information asymmetry about offspring need exists between parents and how such an asymmetry relates to co-adaptation between parental provisioning and offspring begging. Our results show that parents indeed differed in the frequency how often they perceived the playback due to the fact that females spent more time with their offspring in the nest box. Correcting for the effective exposure of an adult to the playback, the parental response in provisioning covaried more strongly (positive) with offspring begging intensity, independent of the parental sex, indicating coadaptation on the phenotypic level. Females were not more sensitive to experimentally increased offspring need than males, but they were exposed to more broadcasted begging calls. Therefore, sex differences in access to information about offspring need, due to different parental roles, have the

  5. The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences

    PubMed Central

    Rice, F.; Harold, G. T.; Boivin, J.; van den Bree, M.; Hay, D. F.; Thapar, A.

    2010-01-01

    Background Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers' characteristics and behaviour during pregnancy which are inherited by offspring. Method A ‘prenatal cross-fostering’ design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother–child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed. Results Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother–offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother–offspring pairs and therefore was attributable to inherited factors. Conclusions Genetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects. PMID:19476689

  6. Maternal high-fat-diet programs rat offspring liver fatty acid metabolism.

    PubMed

    Seet, Emily L; Yee, Jennifer K; Jellyman, Juanita K; Han, Guang; Ross, Michael G; Desai, Mina

    2015-06-01

    In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway. PMID:25899040

  7. Maternal methyl supplemented diets and effects on offspring health

    PubMed Central

    O'Neill, Rachel J.; Vrana, Paul B.; Rosenfeld, Cheryl S.

    2014-01-01

    Women seeking to become pregnant and pregnant women are currently advised to consume high amounts of folic acid and other methyl donors to prevent neural tube defects in their offspring. These diets can alter methylation patterns of several biomolecules, including nucleic acids, and histone proteins. Limited animal model data suggests that developmental exposure to these maternal methyl supplemented (MS) diets leads to beneficial epimutations. However, other rodent and humans studies have yielded opposing findings with such diets leading to promiscuous epimutations that are likely associated with negative health outcomes. Conflict exists to whether these maternal diets are preventative or exacerbate the risk for Autism Spectrum Disorders (ASD) in children. This review will discuss the findings to date on the potential beneficial and aversive effects of maternal MS diets. We will also consider how other factors might influence the effects of MS diets. Current data suggest that there is cause for concern as maternal MS diets may lead to epimutations that underpin various diseases, including neurobehavioral disorders. Further studies are needed to explore the comprehensive effects maternal MS diets have on the offspring epigenome and subsequent overall health. PMID:25206362

  8. Effect of maternal exposure to ozone on reproductive outcome and immune, inflammatory, and allergic responses in the offspring

    EPA Science Inventory

    There is growing concern that exposure to air pollutants during pregnancy affects health outcomes in the offspring due to alterations in the development of immune and other homeostatic processes. To assess the risks of maternal inhalation exposure to ozone (O3), timed pregnant BA...

  9. Pregnant Guppy in Flight

    NASA Technical Reports Server (NTRS)

    1960-01-01

    The Pregnant Guppy is a modified Boeing B-377 Stratocruiser used to transport the S-IV (second) stage for the Saturn I launch vehicle between manufacturing facilities on the West coast, and testing and launch facilities in the Southeast. The fuselage of the B-377 was lengthened to accommodate the S-IV stage and the plane's cabin section was enlarged to approximately double its normal volume. The idea was originated by John M. Conroy of Aero Spaceliners, Incorporated, in Van Nuys, California. The former Stratocruiser became a B-377 PG: the Pregnant Guppy. This photograph depicts the Pregnant Guppy in flight.

  10. Low Folate and Selenium in the Mouse Maternal Diet Alters Liver Gene Expression Patterns in the Offspring after Weaning

    PubMed Central

    Barnett, Matthew P.G.; Bermingham, Emma N.; Young, Wayne; Bassett, Shalome A.; Hesketh, John E.; Maciel-Dominguez, Anabel; McNabb, Warren C.; Roy, Nicole C.

    2015-01-01

    During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring. PMID:26007332

  11. Maternal Patterns of Marijuana Use and Early Sexual Behavior in Offspring of Teenage Mothers

    PubMed Central

    Goldschmidt, Lidush; Cornelius, Marie D.

    2015-01-01

    Teenage mothers use marijuana more frequently than older mothers, and marijuana use may predict HIV risk behavior in offspring. Our goals were to (1) describe trajectories of marijuana use in teenage mothers and (2) determine if these trajectories were associated with early sexual behavior in their offspring. Pregnant adolescents (12–18 years) were recruited at a prenatal clinic and interviewed during pregnancy, at delivery, and during follow-up visits when offspring were 6, 10, 14 and 16 years old. At 16 years, 332 women (71 % Black, 29 % White) and their offspring were assessed. Mothers were asked about their marijuana use at each time point. Offspring reported on their sexual behavior at age 14. Trajectory analyses using growth mixture models revealed four maternal patterns of marijuana use: no use, only at the 6 year follow-up, quit by the 16 year follow-up, and used across most of the time points. The children of chronic users were more likely to have early sex. The maternal marijuana trajectory group variable remained a statistically significant predictor in multivariate models controlling for race, gender, socioeconomic status, child pubertal timing, child externalizing behavior problems, and child marijuana use. These findings suggest that a minority of teenage mothers continue to use marijuana over time. Chronic maternal marijuana use across a decade was associated with early sex in offspring (oral or vaginal sex by age 14). Early sexual behavior places these children at significantly higher risk of teenage pregnancy and HIV risk behaviors. PMID:24942139

  12. Maternal patterns of marijuana use and early sexual behavior in offspring of teenage mothers.

    PubMed

    De Genna, Natacha M; Goldschmidt, Lidush; Cornelius, Marie D

    2015-03-01

    Teenage mothers use marijuana more frequently than older mothers, and marijuana use may predict HIV risk behavior in offspring. Our goals were to (1) describe trajectories of marijuana use in teenage mothers and (2) determine if these trajectories were associated with early sexual behavior in their offspring. Pregnant adolescents (12-18 years) were recruited at a prenatal clinic and interviewed during pregnancy, at delivery, and during follow-up visits when offspring were 6, 10, 14 and 16 years old. At 16 years, 332 women (71 % Black, 29 % White) and their offspring were assessed. Mothers were asked about their marijuana use at each time point. Offspring reported on their sexual behavior at age 14. Trajectory analyses using growth mixture models revealed four maternal patterns of marijuana use: no use, only at the 6 year follow-up, quit by the 16 year follow-up, and used across most of the time points. The children of chronic users were more likely to have early sex. The maternal marijuana trajectory group variable remained a statistically significant predictor in multivariate models controlling for race, gender, socioeconomic status, child pubertal timing, child externalizing behavior problems, and child marijuana use. These findings suggest that a minority of teenage mothers continue to use marijuana over time. Chronic maternal marijuana use across a decade was associated with early sex in offspring (oral or vaginal sex by age 14). Early sexual behavior places these children at significantly higher risk of teenage pregnancy and HIV risk behaviors. PMID:24942139

  13. The Effect of Parents' Attitudes toward Divorce on Offspring's Attitudes: Gender and Parental Divorce as Mediating Factors

    ERIC Educational Resources Information Center

    Kapinus, Carolyn A.

    2004-01-01

    This study addresses three questions: (a) What influence do parents' attitudes toward divorce have on offspring's attitudes? (b) How are offspring's attitudes toward divorce influenced by parental divorce, and do the effects vary depending on the gender of the child? and (c) How do conditions surrounding parental divorce influence young adults'…

  14. Travelers' Health: Pregnant Travelers

    MedlinePlus

    ... animals presents risk of trauma to the abdomen. INFECTIOUS DISEASES Pregnant women who develop travelers’ diarrhea or other ... and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Global Migration and Quarantine (DGMQ) ...

  15. Toxoplasmosis and Pregnant Women

    MedlinePlus

    ... mouth after changing a litter box, or while gardening without gloves. Fruits and vegetables may have contact ... pregnant. Keep outdoor sandboxes covered. Wear gloves when gardening and during contact with soil or sand because ...

  16. Maternal infection during late pregnancy increases anxiety- and depression-like behaviors with increasing age in male offspring.

    PubMed

    Enayati, Mohsen; Solati, Jalal; Hosseini, Mohammad-Hassan; Shahi, Hamid-Reza; Saki, Golshid; Salari, Ali-Akbar

    2012-02-10

    Scientific reports suggest that the exposure to long-term stressors throughout or during late gestation increase anxiety- and depression-like behaviors of offspring in their later life. Moreover, several studies concluded that increasing age correlates with increased anxiety behaviors in humans and rodents. In the present study, we assessed the effects of prenatally administration of equal lipopolysaccharide (LPS) doses in various points of late gestation (days 15, 16, and 17) period, on neuroendocrine and immunological responses of pregnant mice, and subsequent long-lasting consequences of anxiety and depression with increasing age in male offspring at postnatal days (PD) 40 and 80. Four hours after the LPS injection, levels of corticosterone (COR) and pro-inflammatory cytokines (PIC) in pregnant mice, as compared to the control dams, were increased significantly. Furthermore, maternal inflammation raised the levels of COR, anxiety- and depression-like behaviors with increasing age in male offspring in comparison with saline male offspring. These data support other studies demonstrating that maternal stress increases the levels of anxiety and depression in offspring. Additionally, our data confirm other findings indicating that increasing age correlates with increased anxiety or depression behaviors in humans and rodents. Findings of this study suggest that time course of an inflammation response or stressor application during various stages of gestation and ages of offspring are important factors for assessing neuropsychiatric disorders. PMID:21893170

  17. Plasticity in offspring contaminant tolerance traits: developmental cadmium exposure trumps parental effects.

    PubMed

    Plautz, Stephanie C; Salice, Christopher J

    2013-07-01

    Parental effects are non-genotypic influences on offspring phenotype that occur via parental phenotypes or environments, while developmental plasticity is phenotypic variation that arises during development in response to environmental cues. We evaluated the relative contribution of these two sources of phenotypic variation on offspring toxicant tolerance in Physa pomilia snails exposed to cadmium. We exposed adult snails to 0, 2, or 20 μg/L cadmium for 7 days, then exposed egg masses collected from these adults to 0 or 2 μg/L cadmium in a factorial design (adult cadmium exposure × egg mass cadmium exposure). Starting at 2 days old, we recorded time to death for hatchlings exposed to 150 μg/L cadmium for 72 h at 8 h intervals. Juveniles hatched from cadmium-exposed egg masses displayed higher cadmium tolerance than juveniles from unexposed egg masses. Among juveniles from egg masses not exposed to cadmium, offspring of parents exposed to 20 μg/L cadmium had higher cadmium tolerance than offspring of parents exposed to 0 or 2 μg/L cadmium. Our results show that both parental effects and developmental plasticity can impact offspring toxicant tolerance and point to the potential importance of both processes in understanding how offspring respond to chemical contaminants. When both parents and offspring are exposed to a toxicant, our results showed that the effects of parental exposure on offspring toxicant tolerance may be eclipsed by the effects of offspring exposure during development. PMID:23661094

  18. Altered gravity effects on mothers and offspring: the importance of maternal behavior

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.

    2001-01-01

    In this paper, I review and discuss recent studies of pregnant, parturient and lactating rat mothers and neonates exposed to hypo- and hypergravity. These studies are revealing new insights into how deviations form Earth-normal gravity may affect fundamental reproductive and ontogenetic processes in mammals. By way of background, I will first briefly summarize the spaceflights that have carried mammalian mothers and their offspring into space.

  19. Acute exposure to ethanol on gestational day 15 affects social motivation of female offspring.

    PubMed

    Varlinskaya, Elena I; Mooney, Sandra M

    2014-03-15

    Alterations in social behavior are a hallmark of many neurodevelopmental disorders in humans. In rodents, social behavior is affected by prenatal insults. The outcomes are dependent on the timing of the insult as well as the sex and age of the animal tested. The limbic system is particularly important for social behavior, and a peak of neurogenesis within this system occurs on gestational day (G)15. Neurons appear particularly vulnerable to ethanol insult around the time they become post-mitotic. We tested the hypothesis that acute exposure to ethanol on G15 would result in significant social behavior deficits. Accordingly, Long Evans pregnant females were injected with ethanol (2.9 g/kg) or an equivalent volume of saline on G15. Offspring were assessed in a modified social interaction test on postnatal day (P) 28, P42, or P75, i.e., during early adolescence, late adolescence, or young adulthood. Prenatal ethanol exposure decreased social investigation in P28 females and transformed social preference into social avoidance in 75-day-old females. Contact behavior, play fighting, and locomotor activity differed as a function of age, but were not significantly affected by ethanol exposure. Males demonstrated significantly more contact behavior and play fighting at P42 than at P28 or P70, whereas there were no age-related changes in females. Adult females showed more locomotor activity than adult males. Overall, prenatal ethanol exposure on G15 enhanced social anxiety in females, with these effects seen in adulthood only. PMID:24355753

  20. Familial transmission of parental mood disorders: unipolar and bipolar disorders in offspring

    PubMed Central

    Oquendo, Maria A; Ellis, Steven P; Chesin, Megan S; Birmaher, Boris; Zelazny, Jamie; Tin, Adrienne; Melhem, Nadine; Burke, Ainsley K; Kolko, David; Greenhill, Laurence; Stanley, Barbara; Brodsky, Beth S; Mann, J John; Brent, David A

    2013-01-01

    Objectives Offspring of depressed parents are at increased risk for psychiatric disorders. Although bipolar disorder (BD) and major depressive disorder (MDD) are both found in the same families, it is not clear whether transmission to offspring of BD or MDD tends to occur from parents with the same mood disorder subtype. The primary hypothesis was that offspring of parents with BD would be at increased risk for BD and other comorbid disorders common to BD such as anxiety and substance use relative to offspring of parents with MDD. Offspring of parents with BD versus those with MDD were also hypothesized to be at greater risk for externalizing disorders, i.e., conduct disorder, attention-deficit hyperactivity disorder, or antisocial personality disorder. Methods Parents (n = 320) with mood disorders and their offspring (n = 679) were studied. Adult offspring were administered the Structured Clinical Interview for DSM-IV Axis I Disorders to establish the presence of psychopathology. Offspring aged 10 to 18-years-old were assessed with the School Aged Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and parents of children under age 10 completed the Child Behavioral Checklist. Data were examined using Cox Proportional Hazard regression. Results There was no difference in hazard of mood disorders in the offspring of parents with BD as compared to offspring of parents with MDD. However, a number of other parent and offspring characteristics increased risk for mood, anxiety, externalizing, and substance use disorders in offspring, including self-reported childhood abuse in parent or offspring, offspring impulsive aggression, and age of onset of parental mood disorder. Conclusions Mood disorders are highly familial independent of whether the parent’s condition is unipolar or bipolar, and considerable overlap in the familial basis of MDD and BD was found. Although parental characteristics had limited influence on risk of offspring

  1. Physiological and behavioral responses in offspring mice following maternal exposure to sulfamonomethoxine during pregnancy.

    PubMed

    Zhang, Qiang; Zhang, Dan; Ye, Kui; Liu, Kaiyong; Sheng, Jie; Liu, Yehao; Hu, Chunqiu; Ruan, Liang; Li, Li; Tao, Fangbiao

    2016-06-15

    Sulfamonomethoxine (SMM), a veterinary antibiotic, is widely used in China. However, the impacts of maternal SMM exposure on neurobehavioral development in early life remain little known. In this study, we investigated the effects of maternal SMM exposure during pregnancy on behavioral and physiological responses in offspring mice. Pregnant mice were randomly divided into three SMM-treated groups, namely low-(10mg/kg/day), medium-(50mg/kg/day), and high-dose (200mg/kg/day), and a control group. The pregnant mice in the SMM-treated groups received SMM by gavage daily from gestational day 1-18, whereas those in the control received normal saline. On postnatal day (PND) 50, spatial memory was assessed using the Morris water maze test, and anxiety was measured using the elevated plus-maze and open field tests. The results showed significantly increased blood glucose in pups whose mothers received a high SMM dose. In addition, maternal SMM exposure increased anxiety-related activities among the offspring; spatial learning and memory were impaired more severely in the male offspring. The contents of tetrahydrobiopterin (BH4) and brain-derived neurotrophic factors (BDNF) on PND 22 were significantly reduced in the male offspring of the high-dose group compared with the controls. These findings indicate that SMM may be identified as a risk factor for cognitive and behavioral development on the basis of gender and that it may be associated with diminished BH4 and BDNF levels early in life. PMID:27173165

  2. The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory.

    PubMed

    Tang, Wei; Cheng, Juan; Wang, Zheng-Yu; Chen, Ke-Yang; Han, Zhen-Min; Wang, Qi-Hong; Yao, Yu-You

    2016-04-23

    In Alzheimer's disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of AβPP, Aβ42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of Aβ42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene. PMID:27128656

  3. Formaldehyde inhalation during pregnancy abolishes the development of acute innate inflammation in offspring.

    PubMed

    Silva Ibrahim, Beatriz; Miranda da Silva, Cristiane; Barioni, Éric Diego; Correa-Costa, Matheus; Drewes, Carine Cristiane; Saraiva Câmara, Niels Olsen; Tavares-de-Lima, Wothan; Poliselli Farsky, Sandra Helena; Lino-dos-Santos-Franco, Adriana

    2015-06-01

    Formaldehyde (FA) is an environmental and occupational pollutant that induces programming mechanisms on the acquired immune host defense in offspring when exposed during the prenatal period. Hence, here we investigated whether the exposure of FA on pregnant rats could affect the development of an innate acute lung injury in offspring induced by lipopolissacaride (LPS) injection. Pregnant Wistar rats were exposed to FA (0.92 mg/m(3)) or vehicle (distillated water), both 1 h/day, 5 days/week, from 1 to 21 days of pregnancy. Non-manipulated rats were used as control. After 30 days of birth, the offspring was submitted to injection of LPS (Salmonella abortus equi, 5 mg/kg, i.p.). Systemic and lung inflammatory parameters were evaluated 24 h later. Exposure to FA during gestation abolished the development of acute lung injury in offspring, as observed by reduced number of leukocytes in the bronchoalveolar fluid (BAL), in the blood and in the bone marrow, and decreased myeloperoxidase activity in the lung. Moreover, phagocytes from BAL presented normal phagocytosis, but reduced oxidative burst. Alterations on the profile of inflammatory cytokines were evidenced by reduced mRNA levels of IL-6 and elevated levels of IL-10 and IFN gamma in the lung tissue. Indeed, mRNA levels of toll-likereceptor-4 and nuclear factor-kappa B translocation into the nucleus were also reduced. Additionally, hyperresponsiveness to methacholine was blunted in the trachea of offspring of FA exposed mothers. Together, our data clearly show that FA exposure in the prenatal period modifies the programming mechanisms of the innate defense in the offspring leading to impaired defense against infections. PMID:25845602

  4. Pre-birth world and the development of the immune system: mum's diet affects our adult health: new insight on how the diet during pregnancy permanently influences offspring health and immune fitness.

    PubMed

    Ferreira, Manuela; Veiga-Fernandes, Henrique

    2014-12-01

    Secondary lymphoid organs form in utero through an inherited and well-established developmental program. However, maternal non-heritable features can have a major impact on the gene expression of the embryo, hence influencing the future health of the offspring. Recently, maternal retinoids were shown to regulate the formation of immune structures, shedding light on the role of maternal nutrition in the genetic signature of emergent immune cells. Here we highlight evidence showing how the maternal diet influences the establishment of the immune system, and we also discuss how unbalanced maternal diets may set the response to infection and vaccination in the progeny. PMID:25382781

  5. Thermoregulatory deficits in adult Long Evans rat exposed perinatally to the antithyroidal drug, propylthiouracil.

    PubMed

    Johnstone, Andrew F M; Gilbert, Mary E; Aydin, Cenk; Grace, Curtis E; Hasegawa, Masashi; Gordon, Christopher J

    2013-01-01

    Developmental exposure to endocrine disrupting drugs and environmental toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (T(c)) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic pituitary thyroid (HPT) axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor. Propylythiouracil (PTU) was used as a prototypical compound because of its well known antithyroidal properties. PTU was added to the drinking water of pregnant rats in concentrations of 0, 1, 2, 3, and 10 ppm from gestational day (GD) 6 through postnatal day (PND) 21. Adult male offspring were implanted with radiotransmitters to monitor Tc and motor activity (MA) and were observed undisturbed at an ambient temperature of 22 °C for 12 consecutive days. Data were averaged into a single 24 hour period to minimize impact of ultradian changes in T(c) and MA. All treatment groups showed a distinct circadian temperature rhythm. Rats exposed to 10 ppm PTU exhibited a marked deviation in their regulated T(c) with a reduction of approximately 0.4 °C below that of controls throughout the daytime period and a smaller reduction at night. Rats exposed to 1 or 2 ppm also had smaller but significant reductions in T(c). MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an antithyroidal drug led to an apparent permanent reduction in T(c) of adult offspring that was independent of changes in MA. PMID:23732561

  6. Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi.

    PubMed

    Nemoda, Z; Massart, R; Suderman, M; Hallett, M; Li, T; Coote, M; Cody, N; Sun, Z S; Soares, C N; Turecki, G; Steiner, M; Szyf, M

    2015-01-01

    Depression affects 10-15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q<0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P=0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring. PMID:25849984

  7. Social and ecological factors influencing offspring survival in wild macaques

    PubMed Central

    Kerhoas, Daphne; Perwitasari-Farajallah, Dyah; Agil, Muhammad; Widdig, Anja

    2014-01-01

    Premature loss of offspring decreases direct fitness of parents. In gregarious mammals, both ecological and social variables impact offspring survival and may interact with each other in this regard. Although a number of studies have investigated factors influencing offspring loss in mammals, we still know very little on how different factors interact with one another. We therefore investigated fetal and infant mortality in 3 large groups of wild crested macaques (Macaca nigra) over a period of up to 5 years by including potential social causes such as maternal dominance rank, male immigration, between group encounters, and ecological conditions such as rainfall in a multivariate survival analysis using Cox proportional hazards model. Infant but not fetal survival was most impaired after a recent takeover of the alpha-male position by an immigrant male. Furthermore, infant survival probability increased when there was an increase in number of group adult females and rainfall. Fetal survival probability also increased with an increase of these 2 factors, but more in high-ranking than low-ranking females. Fetal survival, unlike that of infants, was also improved by an increase of intergroup encounter rates. Our study thus stresses the importance of survival analyses using a multivariate approach and encompassing more than a single offspring stage to investigate the determinants of female direct fitness. We further provide evidence for fitness costs and benefits of group living, possibly deriving from high pressures of both within- and between-group competition, in a wild primate population. PMID:25214754

  8. Risk of Suicide Attempt in Adopted and Nonadopted Offspring

    PubMed Central

    Malone, Stephen M.; Sharma, Anu; Iacono, William G.; McGue, Matt

    2013-01-01

    OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide attempt. METHODS: Participants were drawn from the Sibling Interaction and Behavior Study, which included 692 adopted and 540 nonadopted offspring and was conducted at the University of Minnesota from 1998 to 2008. Adoptees were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadoptees were ascertained from Minnesota birth records. Outcome measures were attempted suicide, reported by parent or offspring, and factors known to be associated with suicidal behavior including psychiatric disorder symptoms, personality traits, family environment, and academic disengagement. RESULTS: The odds of a reported suicide attempt were ∼4 times greater in adoptees compared with nonadoptees (odds ratio: 4.23). After adjustment for factors associated with suicidal behavior, the odds of reporting a suicide attempt were reduced but remained significantly elevated (odds ratio: 3.70). CONCLUSIONS: The odds for reported suicide attempt are elevated in individuals who are adopted relative to those who are not adopted. The relationship between adoption status and suicide attempt is partially mediated by factors known to be associated with suicidal behavior. Continued study of the risk of suicide attempt in adopted offspring may inform the larger investigation of suicidality in all adolescents and young adults. PMID:24019414

  9. Imprinting of cerebral and hepatic cytochrome p450s in rat offsprings exposed prenatally to low doses of cypermethrin.

    PubMed

    Singh, Anshuman; Yadav, Sanjay; Srivastava, Vikas; Kumar, Rakesh; Singh, Dhirendra; Sethumadhavan, Rao; Parmar, Devendra

    2013-08-01

    Oral administration of low doses (1.25 or 2.5 or 5 mg/kg) corresponding to 1/200th or 1/100th or 1/50th of LD50 of cypermethrin, a synthetic type II pyrethroid, to pregnant Wistar rats from gestation day 5 to 21 produced a dose-dependent increase in the expression of xenobiotic metabolizing cytochrome P450 (CYP) 1A-, 2B- and 2E1 in the brain and liver of offsprings postnatally at 3 weeks that persisted up to 12 weeks. This persistent increase in CYPs was associated with alterations in circulating concentrations of testosterone, luteinizing hormone and follicle stimulating hormone, spontaneous locomotor activity and accumulation of cypermethrin in the brain of exposed offsprings. Rechallenge of exposed offsprings at adulthood (12 weeks old) with cypermethrin (p.o., 10 mg/kg × 6 days) led to a much higher increase in the expression of CYPs in the exposed offsprings when compared to the control offsprings treated with cypermethrin. Further, bioinformatic analysis demonstrating absence of specific short interspersed elements in CYPs suggests that persistence in the increase in CYPs in exposed offsprings could be attributed to the imprinting of the cerebral and hepatic CYPs following prenatal exposure to low doses of cypermethrin. This imprinting could be of toxicological relevance as it may modify the response of drugs or environmental exposures in exposed offsprings particularly for those chemicals which require CYP-mediated metabolism to produce their beneficial or toxic effects. PMID:23447098

  10. Executive summary--nutritional care of HIV-infected adolescents and adults, including pregnant and lactating women: what do we know, what can we do, and where do we go from here?

    PubMed

    Raiten, Daniel J; Mulligan, Kathleen; Papathakis, Peggy; Wanke, Christine

    2011-12-01

    The HIV pandemic continues to place an unbearable burden on the international community, with disease prevalence remaining highest in resource-limited settings in Africa, Asia, and the Americas. HIV is most often imposed on conditions of food insecurity and consequent malnutrition, poor sanitation, and chronic exposure to a myriad of infectious (eg, malaria, tuberculosis, and diarrheal) and noncommunicable (eg, obesity, diabetes, cancer, and cardiovascular) diseases. Women and children continue to bear the greatest burden. Two essential tenets underpin our approach to HIV: 1) antiretroviral drugs (ARVs) are essential to prolong lives and to halt the spread of HIV and AIDS and 2) food and sound nutrition are essential to human health. The challenge is to apply sound principles of clinical care and nutrition science to the safe and efficacious implementation of ARVs and for long-term care for people living with HIV and AIDS. The WHO has played a leading role in developing guidelines to support this goal with the generation of general recommendations regarding nutritional needs of people living with HIV and AIDS and specific guidelines for the nutritional care of HIV-infected infants and children (<14 y of age). These proceedings represent a summary of the work accomplished at a workshop sponsored by the NIH to review the existing evidence to support changes in the recommendations regarding nutrient requirements for people living with HIV and AIDS; to support development of new WHO guidelines for adolescents and adults, including for pregnant and lactating women; and to identify a research agenda to address outstanding knowledge gaps. PMID:22089438

  11. Deep, prolonged torpor by pregnant, free-ranging bats

    NASA Astrophysics Data System (ADS)

    Willis, Craig K. R.; Brigham, R. Mark; Geiser, Fritz

    2006-02-01

    Many mammals save energy during food shortage or harsh weather using controlled reductions in body temperature and metabolism called torpor. However, torpor slows offspring growth, and reproductive individuals are thought to avoid using it because of reduced fitness resulting from delayed offspring development. We tested this hypothesis by investigating torpor during reproduction in hoary bats ( Lasiurus cinereus, Vespertilionidae) in southern Canada. We recorded deep, prolonged torpor bouts, which meet the definition for hibernation, by pregnant females. Prolonged torpor occurred during spring storms. When conditions improved females aroused and gave birth within several days. Our observations imply a fitness advantage of torpor in addition to energy conservation because reduced foetal growth rate could delay parturition until conditions are more favourable for lactation and neonatal survival.

  12. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    PubMed Central

    2016-01-01

    Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats. PMID:27230461

  13. Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring

    PubMed Central

    Schöll, Isabella; Ackermann, Ute; Özdemir, Cevdet; Blümer, Nicole; Dicke, Tanja; Sel, Serdar; Sel, Sarper; Wegmann, Michael; Szalai, Krisztina; Knittelfelder, Regina; Untersmayr, Eva; Scheiner, Otto; Garn, Holger; Jensen-Jarolim, Erika; Renz, Harald

    2010-01-01

    The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30–50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. PMID:17227952

  14. Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring.

    PubMed

    Schöll, Isabella; Ackermann, Ute; Ozdemir, Cevdet; Blümer, Nicole; Dicke, Tanja; Sel, Serdar; Sel, Sarper; Wegmann, Michael; Szalai, Krisztina; Knittelfelder, Regina; Untersmayr, Eva; Scheiner, Otto; Garn, Holger; Jensen-Jarolim, Erika; Renz, Harald

    2007-04-01

    The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. PMID:17227952

  15. Parental age and characteristics of the offspring.

    PubMed

    Liu, Yongsheng; Zhi, Mingxing; Li, Xiuju

    2011-01-01

    The relations of an offspring to its parents are complex, and the ways in which a parent may influence the characteristics of its offspring are many. This review focuses on the relations of parental age to intelligence, health outcomes, longevity and other characteristics of offspring. Many researchers have demonstrated that children of older parents tend to be more intelligent than do children of younger parents, although there are also some negative findings. Either teenage or advanced parental age is associated with risk of birth and health outcomes in offspring. Parental age at birth displays a negative association with offspring longevity. Parental age can also influence dominant characters, sex ratio, personality and development process of the offspring. To fully analyze the influence of parental age on the offspring is of great significance in deciding the optimal age for parenthood. PMID:20887815

  16. The Effects of Sugammadex on Progesterone Levels in Pregnant Rats

    PubMed Central

    Et, Tayfun; Topal, Ahmet; Erol, Atilla; Tavlan, Aybars; Kılıçaslan, Alper; Uzun, Sema Tuncer

    2015-01-01

    Background: Sugammadex has been shown to decrease the efficiency of progesterone-containing oral contraceptive drugs which possess a steroid structure. Aims: The aim of the present study was to evaluate the effects of sugammadex on progesterone levels in pregnant rats as well as on the physiological course of the pregnancy. Study Design: Animal experiment. Methods: This study was approved by the Selçuk University Ethical Committee for Experimental Animal Research. Pregnant Winster Albino rats (n=26) were divided into three groups and administered with various intravenous injections on the 7th day of pregnancy. The control group (Group K, n=6) received 1.5 mL serum physiologic, the sugammadex group (Group S, n=10) received 30 mg/kg sugammadex and the sugammadex + rocuronium group (Group SR, n=10) received 30 mg/kg sugammadex and 3.5 mg/kg rocuronium. Progesterone levels were measured and the offspring were monitored for morphologic status. Results: Mean progesterone levels were 94.16±15.54 ng/mL in Group K, 87.86±12.48 ng/mL in Group S, and 94.53±16.10 ng/mL in Group SR (p>0.05). No stillbirth or miscarriage was observed in the rats. The mean number of offspring was 6.8±1.47 in Group K, 6.5±1.35 in Group S, and 6.4±1.17 in Group SR. The offspring appeared macroscopically normal. Conclusion: Sugammadex does not appear to affect the progesterone levels in pregnant rats in the first trimester and the clinical course. Successful completion of pregnancy and the absence of stillbirth or miscarriage will guide future studies about the use of sugammadex, particularly in the first trimester of the pregnancy. PMID:26167346

  17. The Effects of Food Limitation on Life History Tradeoffs in Pregnant Male Gulf Pipefish

    PubMed Central

    Paczolt, Kimberly A.; Jones, Adam G.

    2015-01-01

    Syngnathid fishes (pipefishes, seahorses and seadragons) are characterized by a unique mode of paternal care in which embryos develop on or in the male’s body, often within a structure known as a brood pouch. Evidence suggests that this pouch plays a role in mediating postcopulatory sexual selection and that males have some control over the events occurring within the pouch during the pregnancy. These observations lead to the prediction that males should invest differently in broods depending on the availability of food. Here, we use the Gulf pipefish to test this prediction by monitoring growth rate and offspring survivorship during the pregnancies of males under low- or high-food conditions. Our results show that pregnant males grow less rapidly on average than non-pregnant males, and pregnant males under low-food conditions grow less than pregnant males under high-food conditions. Offspring survivorship, on the other hand, does not differ between food treatments, suggesting that male Gulf pipefish sacrifice investment in somatic growth, and thus indirectly sacrifice future reproduction, in favor of current reproduction. However, a positive relationship between number of failed eggs and male growth rate in our low-food treatments suggests that undeveloped eggs reduce the pregnancy’s overall cost to the male compared to broods containing only viable offspring. PMID:25970284

  18. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

    SciTech Connect

    Maiellaro, Marília; Correa-Costa, Matheus; Vitoretti, Luana Beatriz; Gimenes Júnior, João Antônio; Câmara, Niels Olsen Saraiva; Tavares-de-Lima, Wothan; Farsky, Sandra Helena Poliselli; Lino-dos-Santos-Franco, Adriana

    2014-08-01

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment.

  19. Impact of Ethanol and Saccharin on Fecal Microbiome in Pregnant and Non-Pregnant Mice

    PubMed Central

    Labrecque, Matthew T; Malone, D’eldra; Caldwell, Katharine E; Allan, Andrea M

    2015-01-01

    Research identifying connections between the gastrointestinal flora and human health has developed at a rapid pace. Several studies link the gut microbiome to a variety of biological functions beyond the gastrointestinal tract. Changes in our diets, including the consumption of artificial sweeteners, have profound effects on the composition of the gut microbiome and can, in turn, affect brain function, glucose tolerance, and inflammation. Sweeteners are often used to encourage consumption of agents such as ethanol and nicotine in laboratory studies using rodents. Studies aiming to examine the effects of agents like ethanol on the developing nervous system administer these agents during pregnancy. To date, there have been no studies exploring the impact of the combination of dietary ethanol and saccharin during pregnancy on the gut microbiome in either humans or laboratory animal models. In the study presented, we evaluated the impact of ethanol in either water or saccharin on the fecal microbiome in pregnant and non-pregnant mice using a qPCR approach. We found that the combination of ethanol and saccharin produced different effects than ethanol in water, depending on pregnancy status. Levels of Clostridium were reduced in ethanol-saccharin but not ethanol-water drinking mice, even though the total levels of ethanol consumed were the same for the two groups. Eubacteria were increased in the pregnant, but decreased in the non-pregnant, ethanol-saccharin drinking group. These treatment and pregnancy specific changes could impact the development of the offspring. In developing and quality checking our primer sets for these studies we identified several problems within previous research in the field. The technical drawbacks in previous studies, as well as our own study, are discussed. Despite some progress in the ability to study the gut microbiome, more advances and standardization of practices should be established to improve the reliability and validity of

  20. Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

    NASA Technical Reports Server (NTRS)

    Alberts, J. R.; Burden, H. W.; Hawes, N.; Ronca, A. E.

    1996-01-01

    To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

  1. Locomotor activity and sensory-motor developmental alterations in rat offspring exposed to arsenic prenatally and via lactation.

    PubMed

    Gumilar, Fernanda; Lencinas, Ileana; Bras, Cristina; Giannuzzi, Leda; Minetti, Alejandra

    2015-01-01

    Arsenic (As) is one of the most toxic naturally occurring contaminants in the environment. The major source of human exposure to inorganic As (iAs) is through contaminated drinking water. Although both genotoxicity and carcinogenicity derived from this metalloid have been thoroughly studied, the effects of iAs on the development and function of the central nervous system (CNS) have received less attention and only a few studies have focused on neurobehavioral effects. Thus, in order to characterize developmental and behavioral alterations induced by iAs exposure, pregnant Wistar rats were exposed to 0.05 and 0.10 mg/L iAs through drinking water during gestation and lactation. Sensory-motor reflexes in each pup were analyzed and the postnatal day when righting reflex, cliff aversion and negative geotaxis were recorded. Functional Observational Battery (FOB) and locomotor activity in an open field were assessed in 90-day-old offspring. Results show that rats exposed to low iAs concentrations through drinking water during early development evidence a delay in the development of sensory-motor reflexes. Both FOB procedure and open-field tests showed a decrease in locomotor activity in adult rats. This study reveals that exposure to the above-mentioned iAs concentrations produces dysfunction in the CNS mechanisms whose role is to regulate motor and sensory development and locomotor activity. PMID:25725132

  2. Learning of your parent’s BRCA mutation during adolescence or early adulthood: a study of offspring experiences

    PubMed Central

    Bradbury, Angela R.; Patrick-Miller, Linda; Pawlowski, Kimberly; Ibe, Comfort N.; Cummings, Shelly A.; Hlubocky, Fay; Olopade, Olufunmilayo I.; Daugherty, Christopher K.

    2015-01-01

    Objective To examine the experience, comprehension and perceptions of learning of a parent’s BRCA mutation during adolescence and early adulthood, and explore the impact on offspring’s physical and psychosocial well-being. Methods Semi-structured interviews were completed with 22 adult offspring who learned of their parent’s BRCA mutation prior to age 25 years. Data were summarized using qualitative methods and response proportions. Results Offspring reports of the content shared varied; discussion of cancer risks and offspring genetic testing were described more frequently than risk modification strategies. The majority of offspring reported a good understanding of the information shared and no negative aspects for learning this information. Some offspring reported changing their health behaviors after learning of the familial mutation; many tobacco users stopped smoking. Offspring interest in genetic counseling surrounding parent disclosure and genetic testing during adulthood were high. Conclusions Some offspring understand and respond adaptively to early communication of a genetic risk for cancer, and disclosure may foster improved health behaviors during adolescence and young adulthood. Further research is necessary to evaluate how offspring conceptualize and utilize genetic risk and to identify the biopsychosocial factors predictive of adaptive/maladaptive responses to early disclosure of hereditary risk for adult cancer. PMID:18702049

  3. Risk of emotional disorder in offspring of depressed parents: gender differences in the effect of a second emotionally affected parent.

    PubMed

    Landman-Peeters, Karlien M C; Ormel, Johan; Van Sonderen, Eric L P; Den Boer, Johan A; Minderaa, Ruud B; Hartman, Catharina A

    2008-01-01

    In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depression and anxiety disorder. We found that daughters had a higher risk of depression and anxiety than sons and that offspring of depressed mothers had a higher risk of anxiety than offspring of depressed fathers. In addition to these main effects, we found an interaction between parent and offspring gender inasmuch that sons of depressed fathers had the lowest risk of depression and anxiety relative to the other groups. A second affected parent tended to increase risk of depression and significantly increased risk of anxiety. However, this effect of a second affected parent on offspring anxiety was most prominent in daughters when the second affected parent was the father, whereas risk in sons did not increase if the father was affected as well. Our results indicate that paternal and maternal depression similarly and additively increase daughters' risk of emotional disorder, but that sons' risk only increases with maternal depression. Intergenerational transmission of emotional disorder seems strongest when the female gender is involved, either in the form of a daughter or a depressed mother. PMID:17941098

  4. Intrauterine environment and later disease development: infertility treatment and the risk of diabetes in offspring.

    PubMed

    Alcolado, John

    2006-01-01

    The phenotype of an individual, including their susceptibility to disease, is governed by several factors including parental genes and intrauterine environment. Thus, the risk of developing Type 2 diabetes is modulated by the inheritance of specific genetic variants that are slowly being characterised by the techniques of linkage analysis and population association studies using either a candidate gene or genome-wide scan approach. At the same time, evidence has accrued that alterations in the nutritional status of the developing foetus also increase the risk of diabetes in later life. Restricting protein intake in pregnant dams or interfering with placental function increases the risk of diabetes in offspring and light weight babies are more likely to develop Type 2 diabetes as adults than heavier ones. The oocyte plays a key role, since it contains not only the maternal haplotype but other information such as mitochondrial DNA and factors that modulate the expression of genes in the developing foetus. Although the ovaries contain a huge number of primordial follicles, generally each month only one oocyte matures to ovulation. Little is known about the processes that control this phenomenon. Certainly, primordial follicles and oocytes are not all the same, differing especially in mitochondrial DNA content. As women age, the oocytes released are more likely to contain genetic errors, explaining the increased risk of Trisomy 21 with maternal age. It is generally assumed that primordial follicle development and the selection of a single ooctye for ovulation is a random process. This paper suggests that this may not be the case but that a carefully controlled system may allow the mother to release an oocyte that is best suited to the prevailing environment. This would represent an important mechanism for species adaptation. Many human infertility treatments involve pharmacological superovulation, egg harvesting and culture prior to in vitro fertilisation and

  5. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring.

    PubMed

    Wasinski, Frederick; Estrela, Gabriel R; Arakaki, Aline M; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  6. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

    PubMed Central

    Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  7. Hypergravity Effects on the Mother-Offspring System in Mammals

    NASA Technical Reports Server (NTRS)

    Ronca, April E.; Sun, Sid (Technical Monitor)

    2001-01-01

    In 1995, ten pregnant female rats were launched on the Space Shuttle (STS-70) on Gestational day (G) 11 of their 22-day pregnancy as part of the NASA/NIH.Rodent (R)2 Experiment. Following landing on G20, fetuses were harvested from half of the dams, 0 g while the remaining five dams underwent birth. Spaceflight did not interrupt pregnancy, alter litter sizes, or affect body weights or gender ratios of the fetuses or neonates. Analyses of rats exposed to Hypergravity (HG) at 2.0-g, HG 1.75-g, HG 1.5-g were also conducted. Dams were exposed to continuous centrifugation from G I I through G20, with brief daily stops for animal health checks and maintenance. For both the G20 and Birth dams, comparable litter sizes and litter gender ratios were observed across gravity conditions. However, centrifugation-exposed (HG and RC) fetuses and neonates showed significantly lower body masses (p less than 0.05) relative to SC offspring. FIG 2.0-g offspring weighed significantly less than those in all other gravity conditions (p less than 0.05). Changes in the mothers care of the young will be discussed.

  8. Gestational weight gain and offspring longitudinal growth in early life

    PubMed Central

    Diesel, Jill C.; Eckhardt, Cara L.; Day, Nancy L.; Brooks, Maria M.; Arslanian, Silva A.; Bodnar, Lisa M.

    2015-01-01

    Background Excessive gestational weight gain (GWG) increases the risk of childhood obesity, but little is known about its association with infant growth patterns. Aim To examine the GWG-infant growth association. Methods Pregnant women (n=743) self-reported GWG at delivery, which we classified as inadequate, adequate, or excessive based on current guidelines. Offspring weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ (with height-for-age (HAZ) in place of length at 36 months)), and body mass index z-scores (BMIZ) were calculated at birth, 8, 18, and 36 months using the 2006 WHO growth standards. Linear mixed models estimated the change in z-scores from birth to 36 months by GWG. Results The mean (SD) WAZ was −0.22 (1.20) at birth. Overall, WAZ and BMIZ increased from birth to approximately 24 months and decreased from 24 to 36 months, while LAZ/HAZ decreased from birth through 36 months. Excessive GWG was associated with higher offspring WAZ and BMIZ at birth, 8, and 36 months, and higher HAZ at 36 months, compared with adequate GWG. Compared with the same referent, inadequate GWG was associated with smaller WAZ and BMIZ at birth and 8 months. Conclusion Excessive GWG may predispose infants to obesogenic growth patterns while inadequate GWG may not have a lasting impact on infant growth. PMID:26279171

  9. Effects of maternal plasmid GHRH treatment on offspring growth.

    PubMed

    Khan, Amir S; Bodles-Brakhop, Angela M; Fiorotto, Marta L; Draghia-Akli, Ruxandra

    2010-02-23

    To differentiate prenatal effects of plasmid growth hormone-releasing hormone (GHRH) treatment from maternal effects mediated by lactation on long-term growth of offspring, a cross-fostering study was designed. Pregnant sows (n=12) were untreated (n=6) or received either a Wt-GHRH (n=2) or HV-GHRH (n=4) plasmid. At birth, half of each litter was cross-fostered (treated to controls and controls to treated only). Piglets from plasmid-injected sows were heavier at birth (HV-GHRH, 1.65+/-0.07kg; Wt-GHRH, 1.46+/-0.05kg vs. Controls, 1.27+/-0.03kg; P>or=0.001) and at weaning (Wt-GHRH, 6.01+/-0.21kg and HV-GHRH, 6.34+/-0.15kg vs. Controls, 5.37+/-0.14kg; P>or=0.02, respectively). Control piglets cross-fostered to plasmid-injected sows grew faster to weaning (Wt-GHRH, 5.61+/-0.15kg and HV-GHRH, 5.70+/-0.29kg vs. Controls, 5.08+/-0.22kg; P>0.05, respectively). Piglets from plasmid-injected sows that suckled on control sows were larger than control piglets on control sows (Wt-GHRH, 5.93+/-0.20kg and HV-GHRH, 6.2+/-0.19kg vs. Controls, 5.08+/-0.22kg; P>0.05, respectively), but smaller than their littermates left on their treated mothers. The observed improvements were maintained until the end of the study when the offspring were 170-day-old. The results suggest that the improved growth of offspring of GHRH plasmid-treated sows pre-weaning is attributable to improved maternal performance, while after weaning the effects on the pituitary component are relevant. PMID:20188245

  10. Maternal Smoke Exposure Impairs the Long-Term Fertility of Female Offspring in a Murine Model.

    PubMed

    Camlin, Nicole J; Sobinoff, Alexander P; Sutherland, Jessie M; Beckett, Emma L; Jarnicki, Andrew G; Vanders, Rebecca L; Hansbro, Philip M; McLaughlin, Eileen A; Holt, Janet E

    2016-02-01

    The theory of fetal origins of adult disease was first proposed in 1989, and in the decades since, a wide range of other diseases from obesity to asthma have been found to originate in early development. Because mammalian oocyte development begins in fetal life it has been suggested that environmental and lifestyle factors of the mother could directly impact the fertility of subsequent generations. Cigarette smoke is a known ovotoxicant in active smokers, yet disturbingly 13% of Australian and 12% of US women continue to smoke throughout pregnancy. The focus of our investigation was to characterize the adverse effects of smoking on ovary and oocyte quality in female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 wk throughout pregnancy/lactation, and ovary and oocyte quality of the F1 (maternal smoke exposed) generation was examined. Neonatal ovaries displayed abnormal somatic cell proliferation and increased apoptosis, leading to a reduction in follicle numbers. Further investigation found that altered somatic cell proliferation and reduced follicle number continued into adulthood; however, apoptosis did not. This reduction in follicles resulted in decreased oocyte numbers, with these oocytes found to have elevated levels of oxidative stress, altered metaphase II spindle, and reduced sperm-egg interaction. These ovarian and oocyte changes ultimately lead to subfertility, with maternal smoke-exposed animals having smaller litters and also taking longer to conceive. In conclusion, our results demonstrate that in utero and lactational exposure to cigarette smoke can have long-lasting effects on the fertility of the next generation of females. PMID:26764348

  11. Coadaptation of offspring begging and parental provisioning--an evolutionary ecological perspective on avian family life.

    PubMed

    Estramil, Natalia; Eens, Marcel; Müller, Wendt

    2013-01-01

    Offspring begging and parental provisioning are the two central social behaviours expressed during the period of parental care. Both behaviours influence each other and it is, therefore, hypothesized that they should ultimately become (genetically) correlated, stabilized by fitness costs to parents and/or offspring. By reciprocally exchanging entire clutches in canaries (Serinus canaria), we tested (1) whether there is covariation between these behaviours and (2) whether a mismatch--as introduced by cross-fostering--entails costs. Begging was scored in a standardized begging test and parental provisioning was measured via (a) the actual feeding rate and (b) using the growth rate of the foster nestlings as a proxy. Costs were established in terms of future reproductive investment in subsequent clutches and offspring growth. We found a positive and significant phenotypic covariation between offspring begging and parental feeding when using the growth rate as a proxy and, to a lesser extent, in case of the parental feeding rate. Female parents suffered no future reproductive costs when feeding foster nestlings that were more demanding than their own nestlings. Neither growth measured amongst all offspring nor the reproductive investment measured amongst the female offspring as adults was influenced by their begging behaviour. However, the reproductive investment of female offspring tended to depend on the parental qualities of their foster parents. Thus, offspring may only be able to extract resources within the limit of generosity of their foster parents. This suggests parental control of feeding, which is also supported by the positive covariation between offspring begging and parental feeding. PMID:23894662

  12. Maternal protein restriction during gestation impairs female offspring pancreas development in the rat.

    PubMed

    Calzada, Lizbeth; Morales, Angélica; Sosa-Larios, Tonantzin C; Reyes-Castro, Luis A; Rodríguez-González, Guadalupe L; Rodríguez-Mata, Verónica; Zambrano, Elena; Morimoto, Sumiko

    2016-08-01

    A maternal low-protein (LP) diet programs fetal pancreatic islet β-cell development and function and predisposes offspring to metabolic dysfunction later in life. We hypothesized that maternal protein restriction during pregnancy differentially alters β- and α-cell populations in offspring by modifying islet ontogeny and function throughout life. We aimed to investigate the effect of an LP maternal diet on pancreatic islet morphology and cellular composition in female offspring on postnatal days (PNDs) 7, 14, 21, 36, and 110. Mothers were divided into 2 groups: during pregnancy, the control group (C) was fed a diet containing 20% casein, and the LP group was fed an isocaloric diet with 10% casein. Offspring pancreases were obtained at each PND and then processed. β and α cells were detected by immunohistochemistry, and cellular area and islet size were quantified. Islet cytoarchitecture and total area were similar in C and LP offspring at all ages studied. At the early ages (PNDs 7-21), the proportion of β cells was lower in LP than C offspring. The proportion of α cells was lower in LP than C offspring on PND 14 and higher on PND 21. The β/α-cell ratio was lower in LP compared with C offspring on PNDs 7 and 21 and higher on PND 36 (being similar on PNDs 14 and 110). We concluded that maternal protein restriction during pregnancy modifies offspring islet cell ontogeny by altering the proportions of islet sizes and by reducing the number of β cells postnatally, which may impact pancreatic function in adult life. PMID:27440540

  13. Coadaptation of Offspring Begging and Parental Provisioning - An Evolutionary Ecological Perspective on Avian Family Life

    PubMed Central

    Estramil, Natalia; Eens, Marcel; Müller, Wendt

    2013-01-01

    Offspring begging and parental provisioning are the two central social behaviours expressed during the period of parental care. Both behaviours influence each other and it is, therefore, hypothesized that they should ultimately become (genetically) correlated, stabilized by fitness costs to parents and/or offspring. By reciprocally exchanging entire clutches in canaries (Serinus canaria), we tested (1) whether there is covariation between these behaviours and (2) whether a mismatch - as introduced by cross-fostering - entails costs. Begging was scored in a standardized begging test and parental provisioning was measured via (a) the actual feeding rate and (b) using the growth rate of the foster nestlings as a proxy. Costs were established in terms of future reproductive investment in subsequent clutches and offspring growth. We found a positive and significant phenotypic covariation between offspring begging and parental feeding when using the growth rate as a proxy and, to a lesser extent, in case of the parental feeding rate. Female parents suffered no future reproductive costs when feeding foster nestlings that were more demanding than their own nestlings. Neither growth measured amongst all offspring nor the reproductive investment measured amongst the female offspring as adults was influenced by their begging behaviour. However, the reproductive investment of female offspring tended to depend on the parental qualities of their foster parents. Thus, offspring may only be able to extract resources within the limit of generosity of their foster parents. This suggests parental control of feeding, which is also supported by the positive covariation between offspring begging and parental feeding. PMID:23894662

  14. Predator-Specific Effects on Incubation Behaviour and Offspring Growth in Great Tits

    PubMed Central

    Basso, Alessandra; Richner, Heinz

    2015-01-01

    In birds, different types of predators may target adults or offspring differentially and at different times of the reproductive cycle. Hence they may also differentially influence incubation behaviour and thus embryonic development and offspring phenotype. This is poorly understood, and we therefore performed a study to assess the effects of the presence of either a nest predator or a predator targeting adults and offspring after fledging on female incubation behaviour in great tits (Parus major), and the subsequent effects on offspring morphological traits. We manipulated perceived predation risk during incubation using taxidermic models of two predators: the short-tailed weasel posing a risk to incubating females and nestlings, and the sparrowhawk posing a risk to adults and offspring after fledging. To disentangle treatment effects induced during incubation from potential carry-over effects of parental behaviour after hatching, we cross-fostered whole broods from manipulated nests with broods from unmanipulated nests. Both predator treatments lead to a reduced on- and off-bout frequency, to a slower decline in on-bout temperature as incubation advanced and showed a negative effect on nestling body mass gain. At the current state of knowledge on predator-induced variation in incubation patterns alternative hypotheses are feasible, and the findings of this study will be useful for guiding future research. PMID:25830223

  15. [Sexuality of pregnant women].

    PubMed

    Malarewicz, Andrzej; Szymkiewicz, Jadwiga; Rogala, Jerzy

    2006-09-01

    Over the time when the sexual intercourse has been considered merely one of a number of forms of sexual contact, views on sexuality during pregnancy have undergone considerable transformation. A great many of authors emphasise, that the pregnancy is a stimulus for partners to search for ways to maintain mutual emotional bond, close physical affinity and satisfy sexual needs not necessarily finished with an intercourse. The fact, that one of the two partners is pregnant, imposes some restrictions on sexual life. Not rarely, in particular in the first trimester of pregnancy, a female is little interested in sex. It is due to, inter alia, hormonal changes resulting in nausea, fatigue and increased nervosity. These symptoms contribute to general feebleness and reduction of the level of sexual needs and difficulty to become aroused and sexually ready. In spite of that, a lot of women have the need to keep physical and emotional contact with their partners. For a number of couples, pregnancy becomes a stimulus to search for new ways of pleasing each other in love play, that does not necessarily leads with an intercourse. Most studies concerning sexuality during pregnancy focus on observing sexual activity, physiological changes, mutual relationship of partners, analysis of sexual intercourses and investigation of so-called sexual satisfaction. Examination of sexual satisfaction ruchedes the frequency of sexual contacts, intercourses, foreplay, concurrence of orgasms in the two partners, partners' happiness, sexual satisfaction and mutual heartiness. In some researchers' opinion, sexual satisfaction correlates with the feeling of happiness resulting form being pregnant, pregnant woman's feeling still attractive and experience of orgasm. However, some researchers observe reduced sexual activity during pregnancy, except for the second trimester, when sexual activity is similar to the one outside pregnancy. Pregnant women prefer the following types of sexual activity: non

  16. Infectious Offspring: How Birds Acquire and Transmit an Avian Polyomavirus in the Wild

    PubMed Central

    Potti, Jaime; Blanco, Guillermo; Lemus, Jesús Á.; Canal, David

    2007-01-01

    Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an ‘upwards vertical’ route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care. PMID:18060070

  17. Scaling of Foraminifera Parent and Offspring Size through the Phanerozoic

    NASA Astrophysics Data System (ADS)

    Guo, D.; Holme, F.; Payne, J.; Skotheim, J.

    2011-12-01

    Since before the 1940s, scientists have studied the scaling of body mass with metabolic rate, heart rate, fecundity, cardiac cycling rate, and numerous other traits. Like these traits, offspring mass scales with parent body mass for plants and animals. However, the relationship is not well documented in single-celled organisms. In our study, we examined how adult size scales with embryo size in fusulinid foraminifera. Fusulinids, and most other foraminifera, are an exceptional study group because the proloculus (the initial shell chamber) can be used to measure the size of the daughter cell at the time it became independent of its parent. We find that proloculus size increases with adult test size across fusulinid species. This pattern may result because the genomic sizes and the cellular machinery necessary for a larger adult size place limits on how small the initial daughter cell can be.

  18. High sucrose consumption during pregnancy induced ADHD-like behavioral phenotypes in mice offspring.

    PubMed

    Choi, Chang Soon; Kim, Pitna; Park, Jin Hee; Gonzales, Edson Luck T; Kim, Ki Chan; Cho, Kyu Suk; Ko, Mee Jung; Yang, Sung Min; Seung, Hana; Han, Seol-Heui; Ryu, Jong Hoon; Cheong, Jae Hoon; Shin, Chan Young

    2015-12-01

    In recent years, the average consumption of sugar in humans from all ages has remarkably increased, exceeding the recommended limit. Pregnancy is a critical time for the global development of offsprings who are vulnerable to the deleterious effects of environmental factors. In this study, we investigated whether high sucrose consumption during pregnancy could affect the attention-deficit hyperactivity disorder (ADHD)-like neurobehavioral outcomes in offspring mice. Pregnant mice were randomly grouped and orally administered with either water as control (Con) or 30% wt/vol sucrose diluted in water at 6 (Suc6) or 9 (Suc9) g/kg dosage per day from gestational days 6 to 15. After the weaning period, offspring mice underwent a series of behavioral testing for locomotor activity, attention, and impulsivity. Although there is no obvious difference in gross development of offspring mice such as weight gain, high sucrose-exposed offspring mice showed a significantly increased locomotor activity. Moreover, these mice exhibited a dose-dependent decrease in attention and increase in impulsivity. In the striatum, a significantly increased dopamine transporter (DAT) mRNA expression was found in the Suc9 group along with dose-dependent decreases in the Drd1, Drd2 and Drd4 dopamine receptor subtypes. Furthermore, synaptosomal DAT protein expression was increased about twofold in the Suc9 group. Prenatal fructose exposure also induced hyperactive behavior in offspring mice suggesting the essential role of fructose in the dysregulated neurobehavioral development. These findings suggest prenatal sucrose consumption as a new risk factor for ADHD, which may need further attention and investigation in humans. PMID:26452319

  19. Fibronectin Regulation by Vitamin C Treatment in Kidneys of Nicotinic Mice Offspring

    PubMed Central

    Pahang, Hasan; Nikravesh, Mohammad Reza; Jalali, Mehdi; Ebrahimzadeh Bideskan, Alireza; Zargari, Peyman; Sadr Nabavi, Ariane

    2014-01-01

    Background: Maternal cigarette smoking causes health risks and developmental defects in the offspring. So far, many studies have been conducted to suppress the effects of nicotine. However, the effects of coadministration of vitamin C and nicotine on extracellular matrix have not gained enough attention. Objectives: This study decided to investigate the effects of vitamin C on fibronectin expression in kidneys of mice offspring, treated with nicotine. Materials and Methods: Eighteen female pregnant BALB/c mice were selected; six mice in the experimental group 1 (exp 1) received nicotine (3 mg/kg/day), six mice in the experimental group 2 (exp 2) received 3 mg/kg/day nicotine and 9 mg/kg/day vitamin C simultaneously, and six were used as the control group and received 3 mL/kg/day normal saline via intraperitoneal (IP) injection parallel to other groups, since the 6th day of gestation to the end of prenatal period. In the first days of delivery, fibronectin content of neonatal kidneys was studied by immunohistochemistry (IHC) assay and gene expression was studied by the real-time PCR. Results: IHC results showed that fibronectin reaction significantly increased in proximal convoluted tubules of exp 1 compared with the control offspring; on the other hand, fibronectin reaction decreased in the mice offspring of exp 2. Gene expression results showed that fibronectin expression in the exp 1 offspring significantly increased compared with the control ones and fibronectin expression decreased in the mice offspring of exp 2. Conclusions: This study revealed that vitamin C could reduce the fibronectin accumulation effects of nicotine on kidney. PMID:25237577

  20. Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: potential role of enhanced maternal immune activity?

    PubMed

    Canuti, Marta; Buka, Stephen; Jazaeri Farsani, Seyed Mohammad; Oude Munnink, Bas B; Jebbink, Maarten F; van Beveren, Nico J M; de Haan, Lieuwe; Goldstein, Jill; Seidman, Larry J; Tsuang, Ming T; Storosum, Jitschak G; van der Hoek, Lia

    2015-08-01

    Viral infections during the prenatal or early childhood periods are one of the environmental factors which might play an etiological role in psychoses. Several studies report higher antibody levels against viruses during pregnancy in blood of mothers of offspring with psychotic disorders, but the presence of such viruses has never been demonstrated. The goal of this study was to investigate the potential association between viral infections during pregnancy and progeny with psychotic disorders and, for this purpose, we performed a nested case-control study involving pregnant mothers of offspring with schizophrenia or bipolar disorder with psychotic features (cases, N=43) and pregnant women with healthy offspring (controls, N=95). Since several potential viral candidates have been suggested in prior work, a broad-spectrum virus detection system was necessary. A metagenomic analysis performed with the virus discovery method VIDISCA-454 revealed only common blood-associated viruses in all cohorts. However, a significantly lower viral prevalence was detected in the group of cases and in the sub-population of pregnant mothers of offspring with schizophrenia (p<0.05). Consistent with the existing inverse correlation between the level of these viruses and the immunocompetence of an individual, we hypothesized the presence of a higher immune activity during pregnancy in mothers whose offspring later develop a psychotic disorder as compared to controls. Combining our results with previously available literature data on antibody levels during the gestation period suggests that a more prominent maternal immune activity can be considered a risk factor for developing psychosis. PMID:26004694

  1. Parent-Offspring Correlations in Pedometer-Assessed Physical Activity

    PubMed Central

    Jacobi, David; Caille, Agnès; Borys, Jean-Michel; Lommez, Agnès; Couet, Charles; Charles, Marie-Aline; Oppert, Jean-Michel

    2011-01-01

    Background Physical activity is a major component of a healthy lifestyle in youth and adults. To identify determinants of this complex behavior is an important research objective in the process of designing interventions to promote physical activity at population level. In addition to individual determinants, there is evidence documenting familial influences on physical activity. However, the few studies that have addressed this issue with objective measures did not provide data on parent-offspring physical activity relationships throughout childhood and adolescence. The purpose of this study was to assess familial correlations in pedometer-assessed physical activity. Methods We measured ambulatory activity in 286 French nuclear families (283 mothers, 237 fathers, and 631 children aged 8–18 years) by pedometer recordings (Yamax Digiwalker DW 450) over a week. Correlations were computed with their 95% confidence intervals (CI) for spouse pairs, siblings, mother-offspring, and father-offspring. Data were expressed as steps per day and computed both for the full recording period and separately for weekdays and weekends. Results The correlations were the highest between siblings (r = 0.28, 95%CI: 0.17–0.38). Parent–offspring correlations were significant in mothers (r = 0.21, 95%CI: 0.12–0.30), especially between mothers and daughters (r = 0.24, 95%CI: 0.12–0.36 vs. r = 0.18, 95%CI: 0.05–0.31 for sons), but were almost nonexistent in fathers. Correlations were generally higher on weekend days compared to weekdays. Mother-offspring correlations did not decrease with increasing age of children (r = 0.17, 95%CI: 0.00–0.34 in 8–11-year-olds, r = 0.20, 95%CI: 0.07–0.33 in 12–15-year-olds, and r = 0.25, 95%CI: 0.07–0.39 in ≥16-year-olds). Finally, between-spouse correlations were significant only during weekend days (r = 0.14, 95%CI: 0.01–0.27). Conclusion Ambulatory activity correlated within families, with a

  2. Furosemide Pharmacokinetics in Adult Rats become Abnormal with an Adverse Intrauterine Environment and Modulated by a Post-Weaning High-Fat Diet.

    PubMed

    DuBois, Barent N; Pearson, Jacob; Mahmood, Tahir; Thornburg, Kent; Cherala, Ganesh

    2016-06-01

    Adult individuals born with intrauterine growth restriction (IUGR) have physiological maladaptations that significantly increase risk of chronic disease. We suggested that such abnormalities in organ function would alter pharmacokinetics throughout life, exacerbated by environmental mismatch. Pregnant and lactating rats were fed either a purified control diet (18% protein) or low-protein diet (9% protein) to produce IUGR offspring. Offspring were weaned onto either laboratory chow (11% fat) or high-fat diet (45% fat). Adult offspring (5 months old) were dosed with furosemide (10 mg/kg i.p.) and serum and urine collected. The overall exposure profile in IUGR males was significantly reduced due to a ~35% increase in both clearance and volume of distribution. Females appeared resistant to the IUGR phenotype. The effects of the high-fat diet trended in the opposite direction to that of IUGR, with increased drug exposure due to decreases in both clearance (31% males, 46% females) and volume of distribution (24% males, 44% females), with a 10% longer half-life in both genders. The alterations in furosemide pharmacokinetics and pharmacodynamics were explained by changes in the expression of renal organic anion transporters 1 and 3, and sodium-potassium-chloride cotransporter-2. In summary, this study suggests that IUGR and diet interact to produce subpopulations with similar body-weights but dissimilar pharmacokinetic profiles; this underlines the limitation of one-size-fits-all dosing which does not account for physiological differences in body composition resulting from IUGR and diet. PMID:26550796

  3. Associations of Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain with Offspring Longitudinal Change in BMI

    PubMed Central

    Lawrence, Gabriella M.; Shulman, Shani; Hochner, Hagit; Sitlani, Colleen M.; Burger, Ayala; Savitsky, Bella; Granot-Hershkovitz, Einat; Lumley, Thomas; Kwok, Pui-Yan; Hasselson, Stephanie; Enquobahrie, Daniel; Wander, Pandora L.; Manor, Orly; Siscovick, David S.; Friedlander, Yechiel

    2013-01-01

    Introduction Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. While maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Objectives We examined associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI), and assessed whether associations are explained by offspring genetics. Design and Methods We used a birth cohort of 1400 adults, with data at birth, age 17 and 32. After genotyping offspring, we created genetic scores, predictive of exposures and outcome, and fit linear regression models with and without scores to examine the associations of mppBMI and GWG with ΔBMI. Results A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m2 increase in ΔBMI respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed. Conclusions This study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for the GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health. PMID:24124160

  4. Offspring ADHD as a Risk Factor for Parental Marital Problems: Controls for Genetic and Environmental Confounds

    PubMed Central

    Schermerhorn, Alice C.; D’Onofrio, Brian M.; Slutske, Wendy S.; Emery, Robert E.; Turkheimer, Eric; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

    2013-01-01

    Background Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. The reasons for this association are unclear, however. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method Data were drawn from the Australian Twin Registry, including 1296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Results Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems. PMID:22958575

  5. Vitamin D status during Pregnancy and Aspects of Offspring Health

    PubMed Central

    Ponsonby, Anne-Louise; Lucas, Robyn M.; Lewis, Sharon; Halliday, Jane

    2010-01-01

    Low maternal vitamin D levels during pregnancy have been linked to various health outcomes in the offspring, ranging from periconceptional effects to diseases of adult onset. Maternal and infant cord 25(OH)D levels are highly correlated. Here, we review the available evidence for these adverse health effects. Most of the evidence has arisen from observational epidemiological studies, but randomized controlled trials are now underway. The evidence to date supports that women should be monitored and treated for vitamin D deficiency during pregnancy but optimal and upper limit serum 25(OH)D levels during pregnancy are not known. PMID:22254029

  6. Evaluating School-Based Programming for Pregnant and Parenting Adolescents.

    ERIC Educational Resources Information Center

    Fenyk, Julie; Maruyama, Geoffrey; Seiden, Katherine; Pain, Lorna; Hoxie, Ann

    The Children and Adolescent Support and Self-Sufficiency (CAPSS) program serves pregnant and parenting adolescents eligible to attend an urban school district in the Midwest. It employs a Youth Development Framework promoting connections with caring adults. While pregnancy prevention has become a major initiative for schools, programming to help…

  7. Disturbed relaxin signaling pathway and testicular dysfunction in mouse offspring upon maternal exposure to simazine.

    PubMed

    Park, Ho-Oak; Bae, Jeehyeon

    2012-01-01

    Simazine is a triazine herbicide that is being widely applied worldwide and commonly detected in surface and groundwater. Despite its popular use in controlling weeds and algae, very limited information is available regarding its toxicity. In the present study, pregnant mice were orally exposed to low doses (0, 5, 50, or 500 µg/kg body weight per day) of simazine during gestation and lactation, during which no overt maternal toxic response was detected, and their offspring was assessed. Simazine-exposed male offspring showed decreased body, testicular, and epididymis weight, increased testicular apoptosis, and decreased sperm concentrations. Differentially-expressed genes in the testes of male offspring exposed to simazine were identified by DNA microarray, revealing 775 upregulated and 791 downregulated genes; among these, the relaxin-family peptide receptor 1 (Rxfp1), which is the receptor for relaxin hormone, was significantly downregulated. In addition, the expression of target genes in the relaxin pathway, including nitric oxide synthase 2 (Nos2) and Nos3, was significantly decreased in simazine-exposed F1 testes. Moreover, simazine inhibited NO release, and knockdown of Rxfp1 blocked the inhibitory action of simazine on NO production in testicular Leydig cells. Therefore, the present study provides a better understanding of the toxicities associated with the widely used herbicide simazine at environmentally relevant doses by demonstrating that maternal exposure interferes with the pleotropic relaxin-NO signaling pathway, impairing normal development and reproductive activity of male offspring. PMID:22984576

  8. Absence of transplacental transmission of Lyme disease spirochetes from reservoir mice (Peromyscus leucopus) to their offspring.

    PubMed

    Mather, T N; Telford, S R; Adler, G H

    1991-09-01

    Lyme disease spirochetes (Borrelia burgdorferi) are naturally maintained in an enzootic cycle mainly by vector ticks (Ixodes dammini) infesting white-footed mice (Peromyscus leucopus). Suggestions that mice may become infected without exposure to ticks prompted a study to evaluate whether mice could transmit spirochetes transplacentally to their offspring. Mice were live-captured in two Massachusetts sites where Lyme disease spirochetes are intensely enzootic. Pregnant females were housed separately in the laboratory through delivery, and mothers and their offspring were caged together until weaning. Each female and two offspring were then examined for evidence of infection serologically and by tick xenodiagnosis. All 14 mother mice examined produced infected ticks and exhibited serum antibodies to B. burgdorferi. However, none of 28 offspring tested produced infected ticks and only a few had evidence of circulating antibody. In a separate experiment, no young CD-1 mice, born of infected mothers, had IgM antibody to B. burgdorferi. It would appear that immature mice are not transplacentally infected with spirochetes and must be exposed to infected ticks before becoming infected and infective themselves. PMID:1869842

  9. Does prenatal restraint stress change the craniofacial growth pattern of rat offspring?

    PubMed

    Aminabadi, Naser A; Behroozian, Ahmad; Talatahari, Elham; Samiei, Mohammad; Sadigh-Eteghad, Saeed; Shirazi, Sajjad

    2016-02-01

    A major and frequently encountered condition underlying the long-term programming effects of the intrauterine environment is exposure to stress. Gestational stress is an environmental factor that induces physical and behavioral alterations in offspring. Seventy female virgin Wistar rats were mated with one male rat for a maximum of four times, after which 52 pregnant rats were divided into two groups. In the experimental group the rats were exposed to restraint stress during pregnancy, whereas the control group did not receive the stress protocol. One male litter was randomly chosen from the offspring of each rat with 8-13 pups. A total of 40 male rat offspring were available for analysis. Thirty-one linear and angular measurements were analyzed in both study groups to investigate whether prenatal restraint stress changes the craniofacial growth pattern of rat offspring. In the prenatally stressed group, anterior cranial base length and viscerocranium measures were significantly increased compared with the control group, whereas cranial width, mandibular dimensions, and posterior cranial height and length remained unchanged. Furthermore, the prenatally stressed group showed backward rotation of the midface and decreased flattening of the cranial vault. It was concluded that prenatal chronic stress can induce alterations in the craniofacial growth pattern by promoting endochondral growth in the cranial base and nasal septum. PMID:26620628

  10. Maternal obesity alters endoplasmic reticulum homeostasis in offspring pancreas.

    PubMed

    Soeda, Jumpei; Mouralidarane, Angelina; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Carter, Rebeca; Kapur, Sabrina R; Pombo, Joaquim; Poston, Lucilla; Taylor, Paul D; Vinciguerra, Manlio; Oben, Jude A

    2016-06-01

    The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p < 0.001) and plasma leptin (p < 0.001) and decreased insulin (p < 0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p < 0.1 to p < 0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults. PMID:26979740

  11. Developmental toxicity of brominated flame retardants, tetrabromobisphenol A and 1,2,5,6,9,10-hexabromocyclododecane, in rat offspring after maternal exposure from mid-gestation through lactation.

    PubMed

    Saegusa, Yukie; Fujimoto, Hitoshi; Woo, Gye-Hyeong; Inoue, Kaoru; Takahashi, Miwa; Mitsumori, Kunitoshi; Hirose, Masao; Nishikawa, Akiyoshi; Shibutani, Makoto

    2009-12-01

    To evaluate developmental exposure effects of two brominated flame retardants, tetrabromobisphenol A (TBBPA) and 1,2,5,6,9,10-hexabromocyclododecane (HBCD), pregnant Sprague-Dawley rats were administered either chemical at doses of 100, 1000 or 10,000 ppm in a soy-free diet from gestation day 10 until the day 20 after delivery. Offspring exposed to TBBPA showed dose-unrelated slight decreases of serum triiodothyronine (T(3)) concentration at postnatal day 20, and there was no evidence of hypothyroidism-related neuronal mismigration and impaired oligodendroglial development as judged by morphometric analyses of NeuN-immunoreactive neuronal distribution in the hippocampal CA1, and area of corpus callosum as well as density of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-immunoreactive oligodendrocytes in the cingulate deep cortex at the adult stage. On the other hand, HBCD exerted a weak hypothyroidism evident with increases in thyroid weight, thyroid follicular cell hypertrophy and serum concentrations of thyroid-stimulating hormone as well as decreases of serum T(3) concentrations in offspring at 10,000 ppm at weaning. Increased thyroid weights and decreased serum T(3) concentrations were also observed in the adult stage from 1000 ppm. With regard to the effect on brain development, HBCD reduced density of CNPase-positive oligodendrocytes at 10,000 ppm, suggesting an impaired oligodendroglial development. Results thus suggest that TBBPA did not exert developmental brain effects, while HBCD did, and 100 ppm was determined to be the no-observed-adverse-effect level of HBCD from changes in thyroid parameters at the adult stage by maternal exposure, translating into 8.1-21.3mg/kg-d. PMID:19577631

  12. Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The intake of carbohydrates has been evaluated cross-sectionally, but not longitudinally in an ageing American adult population. The aim of the present study was to examine trends in the intake of dietary carbohydrates and their major food sources among the Framingham Heart Study Offspring (FOS) coh...

  13. Epigenetic Patterns Modulate the Connection between Developmental Dynamics of Parenting and Offspring Psychosocial Adjustment

    ERIC Educational Resources Information Center

    Naumova, Oksana Yu.; Hein, Sascha; Suderman, Matthew; Barbot, Baptiste; Lee, Maria; Raefski, Adam; Dobrynin, Pavel V.; Brown, Pamela J.; Szyf, Moshe; Luthar, Suniya S.; Grigorenko, Elena L.

    2016-01-01

    This study attempted to establish and quantify the connections between parenting, offspring psychosocial adjustment, and the epigenome. The participants, 35 African American young adults (19 females and 16 males; age = 17-29.5 years), represented a subsample of a 3-wave longitudinal 15-year study on the developmental trajectories of low-income…

  14. Pubertal timing and early sexual intercourse in the offspring of teenage mothers.

    PubMed

    De Genna, Natacha M; Larkby, Cynthia; Cornelius, Marie D

    2011-10-01

    Early puberty is associated with stressful family environments, early sexual intercourse, and teenage pregnancy. We examined pubertal timing and sexual debut among the 14-year-old offspring of teenage mothers. Mothers (71% Black, 29% White) were recruited as pregnant teenagers (12-18 years old). Data were collected during pregnancy and when offspring were 6, 10 and 14 years old (n = 318). Adolescents (50% male) compared the timing of their pubertal maturation to same-sex peers. There was a significant 3-way interaction effect of race, sex, and pubertal timing on sexual debut (n = 305). This effect remained significant in a model controlling for maternal age at first intercourse, substance use, exposure to trauma, authoritative parenting, and peer sexual activity (n = 255). Early maturation was associated with early sex in daughters, and may be one pathway for the inter-generational transfer of risk for teenage pregnancy among daughters of teenage mothers. PMID:21279428

  15. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.

    PubMed

    Choi, Gloria B; Yim, Yeong S; Wong, Helen; Kim, Sangdoo; Kim, Hyunju; Kim, Sangwon V; Hoeffer, Charles A; Littman, Dan R; Huh, Jun R

    2016-02-26

    Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes. PMID:26822608

  16. Current research and prospects for health effects of nanoparticles on offspring

    NASA Astrophysics Data System (ADS)

    Umezawa, Masakazu; Takeda, Ken

    2011-10-01

    Caution in handling ceramic nanoparticles is required by workers and consumers if they are to be used safely and profitably. The small size of nanoparticles can bestow high reactivity and unique translocational properties. Studies have shown that exposure to some types of nanoparticles affects the respiratory, cardiovascular and central nervous systems and various organs. When pregnant mice were exposed to nanoparticles, various organs of offspring are also affected. Our recent studies showed that prenatal exposure to nanoparticles (carbon black and titanium dioxide) causes long-term adverse effects on the reproductive, respiratory and central nervous systems of offspring. The effects of nanoparticles on fetuses and children and the possibility of them leading to the onset of diseases in adulthood are of concern. Thus, it is important to research the risk of unintentional exposure to nanoparticles, including ceramic nanoparticles, from the environment and to attempt to identify methods to protect against their toxicity.

  17. The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring

    PubMed Central

    Choi, Gloria B.; Yim, Yeong S.; Wong, Helen; Kim, Sangdoo; Kim, Hyunju; Kim, Sangwon V.; Hoeffer, Charles A.; Littman, Dan R.; Huh, Jun R.

    2016-01-01

    Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor–related orphan nuclear receptor γt (RORγt)–dependent effector T lymphocytes [e.g., T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes PMID:26822608

  18. Maternally derived carotenoid pigments affect offspring survival, sex ratio, and sexual attractiveness in a colorful songbird

    NASA Astrophysics Data System (ADS)

    McGraw, K. J.; Adkins-Regan, E.; Parker, R. S.

    2005-08-01

    In egg-laying animals, mothers can influence the development of their offspring via the suite of biochemicals they incorporate into the nourishing yolk (e.g. lipids, hormones). However, the long-lasting fitness consequences of this early nutritional environment have often proved elusive. Here, we show that the colorful carotenoid pigments that female zebra finches ( Taeniopygia guttata) deposit into egg yolks influence embryonic and nestling survival, the sex ratio of fledged offspring, and the eventual ornamental coloration displayed by their offspring as adults. Mothers experimentally supplemented with dietary carotenoids prior to egg-laying incorporated more carotenoids into eggs, which, due to the antioxidant activity of carotenoids, rendered their embryos less susceptible to free-radical attack during development. These eggs were subsequently more likely to hatch, fledge offspring, produce more sons than daughters, and produce sons who exhibited more brightly colored carotenoid-based beak pigmentation. Provisioned mothers also acquired more colorful beaks, which directly predicted levels of carotenoids found in eggs, thus indicating that these pigments may function not only as physiological ‘damage-protectants’ in adults and offspring but also as morphological signals of maternal reproductive capabilities.

  19. Maternal obesity during pregnancy and cardiovascular development and disease in the offspring.

    PubMed

    Gaillard, Romy

    2015-11-01

    Maternal obesity during pregnancy is an important public health problem in Western countries. Currently, obesity prevalence rates in pregnant women are estimated to be as high as 30%. In addition, approximately 40% of women gain an excessive amount of weight during pregnancy in Western countries. An accumulating body of evidence suggests a long-term impact of maternal obesity and excessive weight gain during pregnancy on adiposity, cardiovascular and metabolic related health outcomes in the offspring in fetal life, childhood and adulthood. In this review, we discuss results from recent studies, potential underlying mechanisms and challenges for future epidemiological studies. PMID:26377700

  20. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring

    PubMed Central

    Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet

    2015-01-01

    During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. PMID:26578781

  1. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring.

    PubMed

    Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet

    2015-11-17

    During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. PMID:26578781

  2. Assessing the offspring of workaholic parents: the Children of Workaholics Screening Test.

    PubMed

    Robinson, B E; Carroll, J J

    1999-06-01

    This study reports initial stages in the development of a self-report instrument that measures offsprings' mental disposition toward their parents' work habits. In an initial sitting, a battery of tests was administered to 207 young adults to assess the reliability and validity of the Children of Workaholics Screening Test. After a 2-wk. interval, the test was administered again. Test-retest reliability, split-half reliability, and concurrent validity are reported. The findings provide strong support for the utility of the Children of Workaholics Screening Test for assessing the offspring of workaholic parents. PMID:10485093

  3. Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice.

    PubMed

    Zhang, Zhi; van Praag, Henriette

    2015-03-01

    Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic-polyribocytidilic acid (PolyIC, 5mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n=105), was administered systemic bromodeoxyuridine (BrdU, 50mg/kg) (n=52) or intracerebral retroviral injection into the DG (n=53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation. PMID:25449671

  4. Multiple paternity in wild house mice (Mus musculus musculus): effects on offspring genetic diversity and body mass

    PubMed Central

    Thonhauser, Kerstin E; Thoß, Michaela; Musolf, Kerstin; Klaus, Teresa; Penn, Dustin J

    2014-01-01

    Multiple mating is common in many species, but it is unclear whether multiple paternity enhances offspring genetic diversity or fitness. We conducted a survey on wild house mice (Mus musculus musculus), and we found that in 73 pregnant females, 29% of litters had multiple sires, which is remarkably similar to the 23–26% found in feral populations of Mus musculus domesticus in the USA and Australia, respectively. The question is: How has selection maintained multiple mating in these subspecies since the evolutionary divergence, ca. 2800–6000 years ago? We found no evidence that multiple paternity enhanced females’ litter size, contrary to the fertility assurance or genetic benefits hypotheses. Multiple paternity was associated with reduced mean and variance in offspring body mass, which suggests that females allocate fewer resources or that there is increased intrauterine conflict in multiple-versus single-sired litters. We found increased allelic diversity (though not heterozygosity) in multiple-sired litters, as predicted by the genetic diversity hypothesis. Finally, we found that the dams’ heterozygosity was correlated with the mean heterozygosity of their offspring in single-and multiple-sired litters, suggesting that outbred, heterozygous females were more likely to avoid inbreeding than inbred, homozygous females. Future studies are needed to examine how increased genetic diversity of litters and smaller mean (and variance) offspring body mass associated with multiple paternity affect offspring fitness. PMID:24558575

  5. Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: Differential influences of fetal sex.

    PubMed

    Fineberg, Anna M; Ellman, Lauren M; Schaefer, Catherine A; Maxwell, Seth D; Shen, Ling; H Chaudhury, Nashid; Cook, Aundrea L; Bresnahan, Michaeline A; Susser, Ezra S; Brown, Alan S

    2016-02-28

    Exposure to adverse life events during pregnancy has been linked to increased risk of schizophrenia spectrum disorders (SSD) in offspring. Nevertheless, much of the previous work inferred maternal stress from severe life events rather than directly assessing maternal reports of stress. The present study aimed to examine maternal reports of stress during pregnancy and risk for offspring SSD. Participants were 95 SSD cases and 206 controls who were offspring from a large birth cohort study that followed pregnant women from 1959 to 1966. During pregnancy interviews, women were asked if anything worrisome had occurred recently. Interviews were qualitatively coded for stress-related themes, including reports of daily life stress, by two independent raters. None of the maternal psychosocial stress themes were significantly associated with increased odds of offspring SSD in analyses of the full sample. However, results indicated a significant daily life stress by infant sex interaction. Maternal daily life stress during pregnancy was associated with significantly increased odds of SSD among male offspring. Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy. PMID:26753951

  6. Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring

    PubMed Central

    Li, Na; Li, Yongmei; Gao, Qinqin; Li, Dawei; Tang, Jiaqi; Sun, Miao; Zhang, Pengjie; Liu, Bailin; Mao, Caiping; Xu, Zhice

    2015-01-01

    Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2+-activated K+ (BKCa) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BKCa currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage/Ca2+ sensitivity of BKCa channels. BKCa α-subunit expression was unchanged, BKCa β1-subunit and sensitivity of BKCa to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BKCa in the MA. Simultaneous [Ca2+]i fluorescence and vasoconstriction testing showed reduced Ca2+, leading to diminished BKCa activation via ryanodine receptor Ca2+ release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BKCa, providing new information for further understanding increased risks of hypertension in developmental origins. PMID:26277840

  7. Development of anxiety-like behavior via hippocampal IGF-2 signaling in the offspring of parental morphine exposure: effect of enriched environment.

    PubMed

    Li, Chang-Qi; Luo, Yan-Wei; Bi, Fang-Fang; Cui, Tao-Tao; Song, Ling; Cao, Wen-Yu; Zhang, Jian-Yi; Li, Fang; Xu, Jun-Mei; Hao, Wei; Xing, Xiao-Wei; Zhou, Fiona H; Zhou, Xin-Fu; Dai, Ru-Ping

    2014-11-01

    Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure. PMID:24889368

  8. The maternal environment affects offspring viability via an indirect effect of yolk investment on offspring size.

    PubMed

    Warner, Daniel A; Lovern, Matthew B

    2014-01-01

    Environmental conditions that reproductive females experience can influence patterns of offspring provisioning and fitness. In particular, prey availability can influence maternal reproduction and, in turn, affect the viability of their offspring. Although such maternal effects are widespread, the mechanisms by which these effects operate are poorly understood. We manipulated the amount of prey available to female brown anole lizards (Anolis sagrei) to evaluate how this factor affects patterns of reproductive investment (total egg output, egg size, yolk steroids) and offspring viability (morphology, growth, survival). Experimental reduction of yolk in a subset of eggs enabled us to evaluate a potential causal mechanism (yolk investment) that mediates the effect of maternal prey availability on offspring viability. We show that limited prey availability significantly reduced egg size, which negatively influenced offspring size, growth, and survival. Experimental yolk removal from eggs directly reduced offspring size, which, in turn, negatively affected offspring growth and survival. These findings show that maternal environments (i.e., low prey) can affect offspring fitness via an indirect effect of yolk investment on offspring size and highlight the complex set of indirect effects by which maternal effects can operate. PMID:24642545

  9. Stable isotope tracer reveals that viviparous snakes transport amino acids to offspring during gestation.

    PubMed

    Van Dyke, James U; Beaupre, Steven J

    2012-03-01

    Viviparity and placentation have evolved from oviparity over 100 times in squamate reptiles (lizards and snakes). The independent origins of placentation have resulted in a variety of placental morphologies in different taxa, ranging from simple apposition of fetal and maternal tissues to endotheliochorial implantation that is homoplasious with mammalian placentation. Because the eggs of oviparous squamates transport gases and water from the environment and calcium from the eggshell, the placentae of viviparous squamates are thought to have initially evolved to accomplish these functions from within the maternal oviduct. Species with complex placentae have also been shown to rely substantially, or even primarily, on placental transport of organic nutrients for embryonic nutrition. However, it is unclear whether species with only simple placentae are also capable of transporting organic nutrients to offspring. Among viviparous squamates, all of the snakes that have been studied thus far have been shown to have simple placentae. However, most studies of snake placentation are limited to a single lineage, the North American Natricinae. We tested the abilities of four species of viviparous snakes - Agkistrodon contortrix (Viperidae), Boa constrictor (Boidae), Nerodia sipedon (Colubridae: Natricinae) and Thamnophis sirtalis (Colubridae: Natricinae) - to transport diet-derived amino acids to offspring during gestation. We fed [(15)N]leucine to pregnant snakes, and compared offspring (15)N content with that of unlabeled controls. Labeled females allocated significantly more (15)N to offspring than did controls, but (15)N allocation did not differ among species. Our results indicate that viviparous snakes are capable of transporting diet-derived amino acids to their offspring during gestation, possibly via placentation. PMID:22323198

  10. Effects of prenatal exposure to Tityus bahiensis scorpion venom on rat offspring development.

    PubMed

    Dorce, Ana Leticia Coronado; Bellot, Rogério Gentil; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2009-11-01

    Scorpion envenoming is a public health problem. In Brazil, the scorpion Tityus serrulatus is considered the most dangerous, but a large number of exposures also occur with Tityus bahiensis. There are quite a few studies in literature about the toxic effects of this venom but it is not known if the venom causes malformations or behavioral defects to the offspring of mothers exposed to the venom during pregnancy. The objective of this work was to determine, in rats, the possible toxic effects of T. bahiensis venom on offspring when injected into rats during different periods of fetal development. Rats were assigned to one of three groups: one control group and two experimental groups that were subcutaneously injected with venom (2.5mg/kg) on the 10th (GD10) or on 16th day (GD16) of gestation. Pups were evaluated for changes in physical and behavioral development. GD10 treatment group offspring showed an increase in body weight gain, earlier ear unfolding, incisor tooth eruption and vaginal opening. A decrease in the time of palmar grasp and surface-righting reflexes was observed only for males. In GD16 treatment group, earlier ear unfolding, incisor tooth eruption, and delay in eye opening were observed in the offspring. In female pups a decrease in weight gain and in time for palmar grasp reflex, and an increase in time for negative geotaxis were observed. In male pups a delay in the testis descent, decrease in the time of palmar grasp, increase in the time of negative geotaxis reflex and in the general and locomotor activities could be noticed. Therefore, we concluded that a moderate dose of scorpion venom administered to pregnant rats was able to elicit alterations in physical and behavioral development in the offspring during the postnatal period. PMID:19383539

  11. Maternal Stress Induces Epigenetic Signatures of Psychiatric and Neurological Diseases in the Offspring

    PubMed Central

    Zucchi, Fabiola C. R.; Yao, Youli; Ward, Isaac D.; Ilnytskyy, Yaroslav; Olson, David M.; Benzies, Karen; Kovalchuk, Igor; Kovalchuk, Olga; Metz, Gerlinde A. S.

    2013-01-01

    The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through microRNA (miRNA) regulation, responds to prenatal stress in association with epigenetic signatures of psychiatric and neurological diseases. Pregnant Long-Evans rats were assigned to stress from gestational days 12 to 18 while others served as handled controls. Gestational stress in the dam disrupted parturient maternal behaviour and was accompanied by characteristic brain miRNA profiles in the mother and her offspring, and altered transcriptomic brain profiles in the offspring. In the offspring brains, prenatal stress upregulated miR-103, which is involved in brain pathologies, and downregulated its potential gene target Ptplb. Prenatal stress downregulated miR-145, a marker of multiple sclerosis in humans. Prenatal stress also upregulated miR-323 and miR-98, which may alter inflammatory responses in the brain. Furthermore, prenatal stress upregulated miR-219, which targets the gene Dazap1. Both miR-219 and Dazap1 are putative markers of schizophrenia and bipolar affective disorder in humans. Offspring transcriptomic changes included genes related to development, axonal guidance and neuropathology. These findings indicate that prenatal stress modifies epigenetic signatures linked to disease during critical periods of fetal brain development. These observations provide a new mechanistic association between environmental and genetic risk factors in psychiatric and neurological disease. PMID:23451123

  12. Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated with Malpighia emarginata Juice

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; Palhares, Miréia; Martuchi, Karla Aparecida; Oshiiwa, Marie; Sazaki, Viviane; da Silva, Vanessa Sellis

    2011-01-01

    Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola) juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams) treated with water, G2, offspring (of diabetic dams) treated with water, G3, male offspring (of control dams) treated with acerola juice, and G4, male offspring (of diabetic dams) treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases. PMID:21318139

  13. Ontogeny of tetrodotoxin levels in blue-ringed octopuses: maternal investment and apparent independent production in offspring of Hapalochlaena lunulata.

    PubMed

    Williams, Becky L; Hanifin, Charles T; Brodie, Edmund D; Caldwell, Roy L

    2011-01-01

    Many organisms provision offspring with antipredator chemicals. Adult blue-ringed octopuses (Hapalochlaena spp.) harbor tetrodotoxin (TTX), which may be produced by symbiotic bacteria. Regardless of the ultimate source, we find that females invest TTX into offspring and offspring TTX levels are significantly correlated with female TTX levels. Because diversion of TTX to offspring begins during the earliest stages of egg formation, when females are still actively foraging and looking for mates, females may face an evolutionary tradeoff between provisioning larger stores of TTX in eggs and retaining that TTX for their own defense and offense (venom). Given that total TTX levels appear to increase during development and that female TTX levels correlate with those of offspring, investment may be an active adaptive process. Even after eggs have been laid, TTX levels continue to increase, suggesting that offspring or their symbionts begin producing TTX independently. The maternal investment of TTX in offspring of Hapalochlaena spp. represents a rare examination of chemical defenses, excepting ink, in cephalopods. PMID:21165679

  14. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    PubMed Central

    de Castro Barbosa, Thais; Ingerslev, Lars R.; Alm, Petter S.; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M.; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R.; Barrès, Romain

    2015-01-01

    Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations. PMID:26977389

  15. Do prenatal immune activation and maternal iron deficiency interact to affect neurodevelopment and early behavior in rat offspring?

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-01-01

    Infection and iron deficiency are common during pregnancy and studies have described altered brain development in the offspring as a result of these individual maternal exposures. Both exposures have been identified as risk factors for schizophrenia yet they have never been modeled simultaneously. We developed a rat model of prenatal immune activation on a background of maternal iron deficiency to determine whether these factors interact to affect neurodevelopment and early behavior in offspring. Pregnant rats were placed on iron sufficient (IS) or iron deficient (ID) diets from E2 to P7, and administered LPS or saline on E15/16. Iron was reduced in liver, spleen, serum and placenta from ID dams by E15. LPS administration on E15 caused greater induction of serum interleukin-6 and tumor necrosis factor-α in ID dams compared to IS dams. Offspring (P0, P7) from ID dams had reduced iron in spleen, liver and brain compared to IS, which normalized by P21. Pups from ID dams showed differences in forelimb grasp and acoustic startle, whilst pups from LPS dams displayed differences in grip ability, geotaxis reflex, cliff avoidance and acoustic startle. Offspring from LPS dams displayed reduced locomotor activity at P7 and P60; offspring from ID dams showed no change. Our findings show effects of prenatal LPS and maternal iron deficiency were additive, such that offspring exposed to both insults displayed more neurodevelopmental abnormalities than offspring exposed to one alone. Yet surprisingly there was no interaction between factors, suggesting independent mechanisms of action. PMID:24064370

  16. Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women’s Survey

    PubMed Central

    Harvey, Nicholas C.; Moon, Rebecca J.; Sayer, Avan Aihie; Ntani, Georgia; Davies, Justin H.; Javaid, M Kassim; Robinson, Sian M.; Godfrey, Keith M.; Inskip, Hazel M.; Cooper, Cyrus

    2013-01-01

    Context Maternal 25-hydroxy-vitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function but little is known about a role for antenatal 25(OH)D exposure in programming muscle development. Objective We investigated the associations between maternal plasma 25(OH)D status at 34 weeks gestation and offspring lean mass and muscle strength at 4 years of age. Design and setting A prospective UK population-based mother-offspring cohort: the Southampton Women’s Survey (SWS). Participants 12583 non-pregnant women were initially recruited into SWS, of which 3159 had singleton pregnancies. 678 mother-child pairs were included in this analysis. Main Outcomes Measured At 4 years of age, offspring assessments included hand grip strength (Jamar Dynamometer) and whole body DXA (Hologic Discovery) yielding lean mass and %lean mass. Physical activity was assessed by 7-day accelerometry (Actiheart) in a subset of children (n=326). Results Maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength (β=0.10 SD/SD, p=0.013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding and child’s physical activity at 4 years (β=0.13 SD/SD, p=0.014). Maternal 25(OH)D was also positively associated with offspring %lean mass (β=0.11 SD/SD, p=0.006), but not total lean mass (β=0.06, p=0.15). This however did not persist after adjustment for confounding factors (β=0.09 SD/SD, p=0.11). Conclusions This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than muscle mass. PMID:24178796

  17. Maternal Glucose at 28 Weeks of Gestation Is Not Associated With Obesity in 2-Year-Old Offspring

    PubMed Central

    Pettitt, David J.; McKenna, Sonia; McLaughlin, Ciara; Patterson, Christopher C.; Hadden, David R.; McCance, David R.

    2010-01-01

    OBJECTIVE Diabetes during pregnancy is a strong risk factor for obesity in the offspring, but the age at which this association becomes apparent is unknown. The purpose of this study was to examine the relation of glycemia during pregnancy with anthropometry in offspring of nondiabetic pregnant women from the Belfast U.K. center of the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Women from the HAPO Study were invited to participate in follow-up of their offspring aged 2 years. Measurements included height, weight, and thickness of triceps, subscapular, and suprailiac skinfolds. RESULTS A total of 1,165 offspring (73% of eligible children; 598 boys and 567 girls) were seen from ages 22–30 completed months. The only association that reached statistical significance was between categories of maternal 1-h glucose and BMI Z score ≥85th percentile at 2 years (P = 0.017). Overall the correlations between maternal glucose during pregnancy and BMI Z score at age 2 years were weak (fasting glucose r = 0.05, P = 0.08; 1-h glucose r = 0.04, P = 0.22; 2-h glucose r = 0.03, P = 0.36; and area under the curve for glucose r = 0.04, P = 0.18). CONCLUSIONS This study found little association between maternal glucose during pregnancy and obesity in the offspring at this young age. These findings are not unexpected given that study results for young offspring whose mothers had diabetes during pregnancy were indistinguishable from those for normal offspring at this age. It will be interesting to see whether, as these children age, maternal glucose during pregnancy in the ranges included in the HAPO Study will be associated with obesity in their children. PMID:20215449

  18. Prenatal inflammation-induced NF-κB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring

    PubMed Central

    Deng, Youcai; Deng, Yafei; He, Xiaoyan; Chu, Jianhong; Zhou, Jianzhi; Zhang, Qi; Guo, Wei; Huang, Pei; Guan, Xiao; Tang, Yuan; Wei, Yanling; Zhao, Shanyu; Zhang, Xingxing; Wei, Chiming; Namaka, Michael; Yi, Ping; Yu, Jianhua; Li, Xiaohui

    2016-01-01

    Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring’s aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention. PMID:26877256

  19. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M. V. Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications. PMID:21647314

  20. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-08-15

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD{sub 50}; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics.

  1. Polyandry and fitness of offspring reared under varying nutritional stress in decorated crickets.

    PubMed

    Sakaluk, Scott K; Schaus, Jennifer M; Eggert, Anne-Katrin; Snedden, W Andrew; Brady, Pamela L

    2002-10-01

    Females, by mating with more than one male in their lifetime, may reduce their risk of receiving sperm from genetically incompatible sires or increase their prospects of obtaining sperm from genetically superior sires. Although there is evidence of both kinds of genetic benefits in crickets, their relative importance remains unclear, and the extent to which experimentally manipulated levels of polyandry in the laboratory correspond to those that occur in nature remain unknown. We measured lifetime polyandry of free-living female decorated crickets, Gryllodes sigillatus, and conducted an experiment to determine whether polyandry leads to an increase in offspring viability. We experimentally manipulated both the levels of polyandry and opportunities for females to select among males, randomly allocating the offspring of experimental females to high-food-stress or low-food-stress regimes to complete their development. Females exhibited a high degree of polyandry, mating on average with more than seven different males during their lifetime and up to as many as 15. Polyandry had no effect on either the developmental time or survival of offspring. However, polyandrous females produced significantly heavier sons than those of monandrous females, although there was no difference in the adult mass of daughters. There was no significant interaction between mating treatment and offspring nutritional regimen in their effects on offspring mass, suggesting that benefits accruing to female polyandry are independent of the environment in which offspring develop. The sex difference in the extent to which male and female offspring benefit via their mother's polyandry may reflect possible differences in the fitness returns from sons and daughters. The larger mass gain shown by sons of polyandrous females probably leads to their increased reproductive success, either because of their increased success in sperm competition or because of their increased life span. PMID:12449487

  2. Enhanced anxiety in the male offspring of sires that self-administered cocaine.

    PubMed

    White, Samantha L; Vassoler, Fair M; Schmidt, Heath D; Pierce, R Christopher; Wimmer, Mathieu E

    2016-07-01

    We previously showed that paternal cocaine exposure reduced the reinforcing efficacy of cocaine in male offspring. Here, we sought to determine whether paternal cocaine experience could also influence anxiety levels in offspring. Male rats were allowed to self-administer cocaine (controls received saline passively) for 60 days and then were bred with naïve females. Measures of anxiety and cocaine-induced anxiogenic effects were assessed in the adult offspring. Cocaine-sired male offspring exhibited increased anxiety-like behaviors, as measured using the novelty-induced hypophagia and defensive burying tasks, relative to saline-sired males. In contrast, sire cocaine experience had no effect on anxiety-like behaviors in female offspring. When challenged with an anxiogenic (but not anorectic) dose of cocaine (2.5 mg/kg, i.p.), anxiety-like behavior was enhanced in all animals to an equal degree regardless of sire drug experience. Since anxiety and depression are often co-morbid, we also assessed measures of depressive-like behavior. Sire cocaine experience had no effect on depression-like behaviors, as measured by the forced swim task, among male offspring. In a separate group of naïve littermates, select neuronal correlates of anxiety were measured. Male offspring of cocaine-experienced sires showed increased mRNA and protein expression of corticotropin-releasing factor receptor 2 in the hippocampus. Together, these results indicate that cocaine-experienced sires produce male progeny that have increased baseline anxiety, which is unaltered by subsequent cocaine exposure. PMID:25923597

  3. Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

    PubMed Central

    Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

    2016-01-01

    OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

  4. Poor maternal nutrition inhibits muscle development in ovine offspring

    PubMed Central

    2014-01-01

    Background Maternal over and restricted nutrition has negative consequences on the muscle of offspring by reducing muscle fiber number and altering regulators of muscle growth. To determine if over and restricted maternal nutrition affected muscle growth and gene and protein expression in offspring, 36 pregnant ewes were fed 60%, 100% or 140% of National Research Council requirements from d 31 ± 1.3 of gestation until parturition. Lambs from control-fed (CON), restricted-fed (RES) or over-fed (OVER) ewes were necropsied within 1 d of birth (n = 18) or maintained on a control diet for 3 mo (n = 15). Semitendinosus muscle was collected for immunohistochemistry, and protein and gene expression analysis. Results Compared with CON, muscle fiber cross-sectional area (CSA) increased in RES (58%) and OVER (47%) lambs at 1 d of age (P < 0.01); however at 3 mo, CSA decreased 15% and 17% compared with CON, respectively (P < 0.01). Compared with CON, muscle lipid content was increased in OVER (212.4%) and RES (92.5%) at d 1 (P < 0.0001). Muscle lipid content was increased 36.1% in OVER and decreased 23.6% in RES compared with CON at 3 mo (P < 0.0001). At d 1, myostatin mRNA abundance in wh