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…

Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice.

PubMed

Khalyfa, Abdelnaby; Cortese, Rene; Qiao, Zhuanhong; Ye, Honggang; Bao, Riyue; Andrade, Jorge; Gozal, David

2017-04-15

Late gestation during pregnancy has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia, a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis and metabolic function in offspring. Here we show that late gestation intermittent hypoxia induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in visceral white adipose tissue. Fetal perturbations by OSA during pregnancy impose long-term detrimental effects manifesting as metabolic dysfunction in adult male offspring. Pregnancy, particularly late gestation (LG), has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesized that IH during late pregnancy (LG-IH) may increase the propensity for metabolic dysregulation and obesity in adult offspring via epigenetic modifications. Time-pregnant female C57BL/6 mice were exposed to LG-IH or room air (LG-RA) during days 13-18 of gestation. At 24 weeks, blood samples were collected from offspring mice for lipid profiles and insulin resistance, indirect calorimetry was performed and visceral white adipose tissues (VWAT) were assessed for inflammatory cells as well as for differentially methylated gene regions (DMRs) using a methylated DNA immunoprecipitation on chip (MeDIP-chip). Body weight, food intake, adiposity index, fasting insulin, triglycerides and cholesterol levels were all significantly higher in LG-IH male but not female offspring. LG-IH also altered metabolic expenditure and locomotor activities in male offspring, and increased number of pro-inflammatory macrophages emerged in VWAT along with 1520 DMRs (P < 0.0001), associated with 693�

Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence.

PubMed

Thompson, Ronald G; Alonzo, Dana; Hasin, Deborah S

2013-01-01

This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems.

Prenatal Gender-Related Nicotine Exposure Increases Blood Pressure Response to Angiotensin II in Adult Offspring

PubMed Central

Xiao, DaLiao; Xu, Zhice; Huang, Xiaohui; Longo, Lawrence D.; Yang, Shumei; Zhang, Lubo

2008-01-01

Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month–old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II–stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring. In male offspring, nicotine exposure significantly increased Ang II–induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II–induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II–induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca2+ concentrations and Ca2+ sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor–mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring. PMID:18259024

Parental divorce, parental depression, and gender differences in adult offspring suicide attempt.

PubMed

Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

2009-12-01

Research suggests parental divorce during childhood increases risk of suicide attempt for male but not female offspring. The negative impact on offspring associated with parental divorce may be better explained by parental psychopathology, such as depression. We examined whether adult offspring of parental divorce experience elevated risk of suicide attempt, controlling for parental history of depression, and whether the risk varies by the gender of the offspring. Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the sample consists of respondents who experienced parental divorce (N = 4895). Multivariable regressions controlled for age, race/ethnicity, income, marital status, and parental history of depression. Females living with their fathers were significantly more likely to report lifetime suicide attempts than females living with their mothers, even after controlling for parental depression. Findings suggest that childhood/adolescent parental divorce may have a stronger impact on suicide attempt risk in female offspring than previously recognized.

Parental Divorce, Parental Depression, and Gender Differences in Adult Offspring Suicide Attempt

PubMed Central

Lizardi, Dana; Thompson, Ronald G.; Keyes, Katherine; Hasin, Deborah

2013-01-01

Research suggests parental divorce during childhood increases risk of suicide attempt for male but not female offspring. The negative impact on offspring associated with parental divorce may be better explained by parental psychopathology, such as depression. We examined whether adult offspring of parental divorce experience elevated risk of suicide attempt, controlling for parental history of depression, and whether the risk varies by the gender of the offspring. Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the sample consists of respondents who experienced parental divorce (N = 4895). Multivariable regressions controlled for age, race/ethnicity, income, marital status, and parental history of depression. Females living with their fathers were significantly more likely to report lifetime suicide attempts than females living with their mothers, even after controlling for parental depression. Findings suggest that childhood/adolescent parental divorce may have a stronger impact on suicide attempt risk in female offspring than previously recognized. PMID:20010025

A general model for the scaling of offspring size and adult size.

PubMed

Falster, Daniel S; Moles, Angela T; Westoby, Mark

2008-09-01

Understanding evolutionary coordination among different life-history traits is a key challenge for ecology and evolution. Here we develop a general quantitative model predicting how offspring size should scale with adult size by combining a simple model for life-history evolution with a frequency-dependent survivorship model. The key innovation is that larger offspring are afforded three different advantages during ontogeny: higher survivorship per time, a shortened juvenile phase, and advantage during size-competitive growth. In this model, it turns out that size-asymmetric advantage during competition is the factor driving evolution toward larger offspring sizes. For simplified and limiting cases, the model is shown to produce the same predictions as the previously existing theory on which it is founded. The explicit treatment of different survival advantages has biologically important new effects, mainly through an interaction between total maternal investment in reproduction and the duration of competitive growth. This goes on to explain alternative allometries between log offspring size and log adult size, as observed in mammals (slope = 0.95) and plants (slope = 0.54). Further, it suggests how these differences relate quantitatively to specific biological processes during recruitment. In these ways, the model generalizes across previous theory and provides explanations for some differences between major taxa.

Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence

PubMed Central

THOMPSON, RONALD G.; ALONZO, DANA; HASIN, DEBORAH S.

2014-01-01

This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems. PMID:24678271

Later Life Impacts of Social Participation on Parents of Adult Offspring With and Without Intellectual and Developmental Disabilities.

PubMed

Olsen, Darren L

2018-01-01

Social participation is an important resource for parents in old age, and may be particularly important for parents living with adult offspring with intellectual and developmental disabilities. To evaluate whether socializing with friends and family and participating in social organizations protects against depression in old age, this study examined parents of adult offspring with disabilities ( n = 164) and without disabilities ( n = 820). As expected, more socializing with friends and more participating in organizations were associated with fewer depressive symptoms for all parents. However, socializing with family members predicted fewer depressive symptoms only for parents co-residing with their adult offspring with disabilities, suggesting that socializing with family is particularly important for parents providing direct care to adults with disabilities.

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

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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

PubMed

Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

2013-03-01

Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P <0.05) in the PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

PubMed

Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-02-01

Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

PubMed

Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

2015-01-01

Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring.

PubMed

Ramos, Débora R; Costa, Nauilo L; Jang, Karen L L; Oliveira, Ivone B; da Silva, Alexandre A; Heimann, Joel C; Furukawa, Luzia N S

2012-05-22

The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.16% NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA, ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. Copyright © 2012 Elsevier Inc. All rights reserved.

Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

PubMed

Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

2006-05-01

Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

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

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

Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring.

PubMed

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

2010-08-01

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. Copyright 2010 Elsevier Inc. All rights reserved.

Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

PubMed Central

Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

2017-01-01

Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

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

Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

PubMed

Hollander, K S; Tempel Brami, C; Konikoff, F M; Fainaru, M; Leikin-Frenkel, A

2014-07-01

Our objective was to test the contribution of dietary enrichment in essential or saturated fatty acids, in normocaloric diets, on the lipid accumulation and insulin resistance in the adult offspring in a C57Bl6/J mice model. Pregnant mothers were fed normocaloric diets containing 6% fat enriched in essential fatty acids (EFA): alpha-linolenic (ALA-18:3, n-3), linoleic (LA-18:2, n-6), or saturated fatty acids (SFA). After a washing-out period with regular diet, the offspring received a high-fat diet before euthanization. Adult mice fed maternal ALA showed lower body weight gain and lower liver fat accumulation, lower HOMA index and lower stearoyl-CoA desaturase (SCD1) activity than those fed maternal SFA. The results observed using this novel model suggest that ALA in maternal diet may have the potential to inhibit insulin resistance in adult offspring.

Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring

PubMed Central

Odhiambo, John F.; McCormick, Richard J.; Nathanielsz, Peter W.; Ford, Stephen P.

2017-01-01

Obesity during human pregnancy predisposes offspring to obesity and cardiovascular disease in postnatal life. In a sheep model of maternal overnutrition/obesity we have previously reported myocardial inflammation and fibrosis, as well as cardiac dysfunction in late term fetuses, in association with chronically elevated blood cortisol. Significant research has suggested a link between elevated glucocorticoid exposure in utero and hypertension and cardiovascular disease postnatally. Here we examined the effects of maternal obesity on myocardial inflammation and fibrosis of their adult offspring. Adult male offspring from control (CON) mothers fed 100% of National Research Council (NRC) recommendations (n = 6) and male offspring from obese mothers (MO) fed 150% NRC (n = 6), were put on a 12-week ad libitum feeding challenge then necropsied. At necropsy, plasma cortisol and left and right ventricular thickness were markedly increased (P<0.05) in adult male MO offspring. Myocardial collagen content and collagen-crosslinking were greater (P<0.05) in MO offspring compared to CON offspring in association with increased mRNA and protein expression of glucocorticoid receptors (GR). No group difference was found in myocardial mineralocorticoids receptor (MR) protein expression. Further, mRNA expression for the proinflammatory cytokines: cluster of differentiation (CD)-68, transforming growth factor (TGF)-β1, and tumor necrosis factor (TNF)-α were increased (P < 0.05), and protein expression of CD-68, TGF-β1, and TNF-α tended to increase (P<0.10) in MO vs. CON offspring. These data provide evidence for MO-induced programming of elevated plasma cortisol and myocardial inflammation and fibrosis in adult offspring potentially through increased GR. PMID:29267325

Can domestic helpers moderate distress of offspring caregivers of cognitively impaired older adults?

PubMed

Chong, Alice M L; Kwan, Chi Wai; Lou, Vivian W Q; Chi, Iris

2017-10-01

This study examined the moderating effect of domestic helpers on distress of offspring caring for parents with cognitive impairments and with or without behavioural problems. This secondary analysis of data involved 5086 Hong Kong Chinese adults aged 60 or older applying for public long-term care services from 2010 to 2012. All variables were measured using the mandatory Hong Kong version of the Minimum Data Set-Home Care 2.0. Regarding taking care of parents with cognitive impairments, 10.7% of offspring primary caregivers were aided by domestic helpers, 55.54% reported distress, and 75.70% lived with their parents. Assistance from domestic helpers reduced offspring caregiver distress if the offspring provided psychological support to parents (ratio of OR = 0.655, p < .05) and were not living with parents (ratio of OR = 1.183, p < .01). These findings might suggest: a) the positive effects of audience on psychological responses to stress; b) caregiving is usually less stressful for informal caregivers not residing with care recipients. Conversely, having a domestic helper could add to caregiving distress if offspring caregivers live with their parents, most likely because offspring may witness difficulties that domestic helpers face in providing dementia care.

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder.

PubMed

Lizardi, Humberto; Klein, Daniel N; Shankman, Stewart A

2004-03-01

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.

Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring.

PubMed

Segovia, Stephanie A; Vickers, Mark H; Harrison, Claudia J; Patel, Rachna; Gray, Clint; Reynolds, Clare M

2018-01-01

Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl), high-salt (SD; 10% kcal from fat, 4% NaCl), high-fat (HF; 45% kcal from fat, 1% NaCl) or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl) diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1 . There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2 . Gut expression of inflammatory ( Il1r1, Tnfα, Il6 , and Il6r ) and renin-angiotensin system ( Agtr1a, Agtr1b ) markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin-angiotensin regulation.

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

PubMed

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

2012-08-01

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. 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, and 56%; Latin-square) according to a FR-3, and then a progressive-ratio (PR) schedule. Male and female adult offspring were used. 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. 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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy.

PubMed

Guo, Yitian; Luo, Hanwen; Wu, Yimeng; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2018-05-22

Epidemiological surveys suggest that adult hypercholesterolemia has an intrauterine origin and exhibits gender differences. Our previous study demonstrated that adult rats with intrauterine growth retardation (IUGR) offspring rats induced by prenatal caffeine exposure (PCE) had a higher serum total cholesterol (TCH) level. In this study, we aimed to analyze the influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy. Pregnant rats were administered caffeine (120 mg/kg d) from gestational day 11 until delivery. Offspring rats fed a normal diet or a high-fat diet (HFD) were euthanized at postnatal week 24, and blood and liver samples were collected. The results showed that PCE could increase the serum levels of TCH and low-density lipoprotein-cholesterol (LDL-C), and the hepatic expression of HMG CoA reductase (HMGCR) and apolipoprotein B (ApoB), but decreased the high-density lipoprotein-cholesterol (HDL-C) level and the hepatic expression of scavenger receptor B1 (SR-B1) and LDL receptor (LDLR). Furthermore, PCE, HFD and gender interact with each other to influence the serum cholesterol phenotype and expression of hepatic cholesterol metabolic genes. These results suggest that the hypercholesterolemia in adult offspring rats induced by PCE mainly resulted from enhanced synthesis and the weakened reverse transport of cholesterol in the liver, furthermore HFD could aggravate this effect, which is caused by hepatic cholesterol metabolic disorders. Moreover, cholesterol metabolism in female rats was more sensitive to neuroendocrine changes and HFD than that in males. This study confirmed the influencing factors (such as a HFD and female gender) of hypercholesterolemia in IUGR offspring providing theoretical and experimental bases for the effective prevention of fetal-originated hypercholesterolemia. Copyright © 2018 Elsevier Inc. All rights reserved.

Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring?

PubMed Central

Khandaker, G M; Dibben, C R M; Jones, P B

2012-01-01

Summary Maternal obesity in pregnancy has been linked with several adverse outcomes in offspring including schizophrenia. The rising prevalence of obesity may contribute to an increase in the number of schizophrenia cases in the near future; therefore, it warrants further exploration. We reviewed current evidence regarding maternal body mass index (BMI) in pregnancy and risk of schizophrenia in adult offspring. We searched PubMed and Embase databases and included studies that were based on large and representative population-based datasets. A qualitative review was undertaken due to heterogeneity between studies. Four studies with 305 cases of schizophrenia and 24,442 controls were included. Maternal obesity (pre-pregnant BMI over 29 or 30 compared with mothers with low or average BMI) was associated with two- to threefold increased risk of schizophrenia in the adult offspring in two birth cohorts. High maternal BMI at both early and late pregnancy also increased risk of schizophrenia in the offspring. Discrepant findings from one study could be attributable to sample characteristics and other factors. The area needs more research. Future studies should take into account obstetric complications, diabetes, maternal infections and immune responses that might potentially mediate this association. PMID:22188548

Perinatal programming of depressive-like behavior by inflammation in adult offspring mice whose mothers were fed polluted eels: Gender selective effects.

PubMed

Soualeh, Nidhal; Dridi, Imen; Eppe, Gauthier; Némos, Christophe; Soulimani, Rachid; Bouayed, Jaouad

2017-07-01

Several lines of evidence indicate that early-life inflammation may predispose to mental illness, including depression, in later-life. We investigated the impact of perinatal exposure to polluted eels on neonatal, postnatal, and adult brain inflammation, and on the resignation behavior of male and female adult offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Brain inflammatory markers including cytokines were assessed in offspring mice on the day of birth (i.e., on the postnatal day-PND 1), upon weaning (PND 21) and at adulthood (PND 100). Plasma myeloperoxidase and corticosterone levels were evaluated at PND 100. Immobility behavior of offspring was assessed in adulthood (i.e., at PNDs 95-100), using the tail suspension and forced swimming tests. Chronic brain inflammation was found in male and female offspring mice compared to controls, as assessed at PNDs 1, 21, and 100. The level of myeloperoxidase was found to be significantly higher in both adult males and females vs. control offspring. However, high corticosterone levels were only found in male offspring mice that were perinatally exposed to eels, suggesting a gender-selective dysregulation of the adult hypothalamic-pituitaryadrenal (HPA) axis. Gender-specific differences were also detected in adulthood in regard to offspring resignation behavior. Thus, compared to controls, males, but not females, whose mothers were fed eels during pregnancy and lactation exhibited a depressive-like behavior in adult age in both behavioral models of depression. Depressive symptoms were more pronounced in male mice perinatally exposed to either intermediate or highly polluted eels than those exposed to only lowly polluted eels. Our results indicate that early-life inflammatory insult is a plausible causative factor that induces the depressive phenotype exhibited by male adult offspring mice, most likely through a

Prenatal Ethanol Exposure Causes Glucose Intolerance with Increased Hepatic Gluconeogenesis and Histone Deacetylases in Adult Rat Offspring: Reversal by Tauroursodeoxycholic Acid

PubMed Central

Yao, Xing-Hai; Nguyen, Hoa K.; Nyomba, B. L. Grégoire

2013-01-01

Prenatal ethanol exposure results in increased glucose production in adult rat offspring and this may involve modulation of protein acetylation by cellular stress. We used adult male offspring of dams given ethanol during gestation days 1–7 (early), 8–14 (mid) and 15–21 (late) compared with those from control dams. A group of ethanol offspring was treated with tauroursodeoxycholic acid (TUDCA) for 3 weeks. We determined gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, hepatic free radicals, histone deacetylases (HDAC), acetylated foxo1, acetylated PEPCK, and C/EBP homologous protein as a marker of endoplasmic reticulum stress. Prenatal ethanol during either of the 3 weeks of pregnancy increased gluconeogenesis, gluconeogenic genes, oxidative and endoplasmic reticulum stresses, sirtuin-2 and HDAC3, 4, 5, and 7 in adult offspring. Conversely, prenatal ethanol reduced acetylation of foxo1 and PEPCK. Treatment of adult ethanol offspring with TUDCA reversed all these abnormalities. Thus, prenatal exposure of rats to ethanol results in long lasting oxidative and endoplasmic reticulum stresses explaining increased expression of gluconeogenic genes and HDAC proteins which, by deacetylating foxo1 and PEPCK, contribute to increased gluconeogenesis. These anomalies occurred regardless of the time of ethanol exposure during pregnancy, including early embryogenesis. As these anomalies were reversed by treatment of the adult offspring with TUDCA, this compound has therapeutic potentials in the treatment of glucose intolerance associated with prenatal ethanol exposure. PMID:23544086

Sugared water consumption by adult offspring of mothers fed a protein-restricted diet during pregnancy results in increased offspring adiposity: the second hit effect.

PubMed

Cervantes-Rodríguez, M; Martínez-Gómez, M; Cuevas, E; Nicolás, L; Castelán, F; Nathanielsz, P W; Zambrano, E; Rodríguez-Antolín, J

2014-02-01

Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5% sucrose in the drinking-water) on adult offspring adiposity as a 'second hit' following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor - the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion.

Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

PubMed

Gray, Clint; Al-Dujaili, Emad A; Sparrow, Alexander J; Gardiner, Sheila M; Craigon, Jim; Welham, Simon J M; Gardner, David S

2013-01-01

Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young.

Excess Maternal Salt Intake Produces Sex-Specific Hypertension in Offspring: Putative Roles for Kidney and Gastrointestinal Sodium Handling

PubMed Central

Gray, Clint; Al-Dujaili, Emad A.; Sparrow, Alexander J.; Gardiner, Sheila M.; Craigon, Jim; Welham, Simon J.M.; Gardner, David S.

2013-01-01

Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth – a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3–14.8] vs. 2.8 [2.0–8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9–21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young. PMID

Developmental cigarette smoke exposure II: Hepatic proteome profiles in 6 month old adult offspring.

PubMed

Neal, Rachel E; Chen, Jing; Webb, Cindy; Stocke, Kendall; Gambrell, Caitlin; Greene, Robert M; Pisano, M Michele

2016-10-01

Utilizing a mouse model of 'active' developmental cigarette smoke exposure (CSE) [gestational day (GD) 1 through postnatal day (PD) 21] characterized by offspring low birth weight, the impact of developmental CSE on liver proteome profiles of adult offspring at 6 months of age was determined. Liver tissue was collected from Sham- and CSE-offspring for 2D-SDS-PAGE based proteome analysis with Partial Least Squares-Discriminant Analysis (PLS-DA). A similar study conducted at the cessation of exposure to cigarette smoke documented decreased gluconeogenesis coupled to oxidative stress in weanling offspring. In the current study, exposure throughout development to cigarette smoke resulted in impaired hepatic carbohydrate metabolism, decreased serum glucose levels, and increased gluconeogenic regulatory enzyme abundances during the fed-state coupled to decreased expression of SIRT1 as well as increased PEPCK and PGC1α expression. Together these findings indicate inappropriately timed gluconeogenesis that may reflect impaired insulin signaling in mature offspring exposed to 'active' developmental CSE. Copyright © 2016 Elsevier Inc. All rights reserved.

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

PubMed

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation.

PubMed

Hsueh, P-T; Lin, H-H; Wang, H-H; Liu, C-L; Ni, W-F; Liu, J-K; Chang, H-H; Sun, D-S; Chen, Y-S; Chen, Y-L

2018-04-15

The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that upregulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring. In this study, a C57BL/6j MIA female offspring model exhibiting social deficits was established. The expression of fetal interferon (IFN)-stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic upregulation of endogenous IL-10 occurred at the adult stage, while both IL-1β and IL-6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL-6 levels were endogenously upregulated, but both MCP-1 (macrophage inflammatory protein-1) and L-selectin levels were downregulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting the MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines, chemokines and CAMs were increased. Particularly, both MCP-1 and L-selectin showed relatively high expression in the brain compared with the expression levels in phosphate-buffered saline (PBS)-treated offspring injected with LPS. Potentially, MCP-1 was attracted to the L-selectin-mediated immune cells due to augmentation of the immune response following stimulation in MIA female offspring. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

PubMed Central

Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

2016-01-01

A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

Levels of maternal care in dogs affect adult offspring temperament

NASA Astrophysics Data System (ADS)

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.

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.

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring

PubMed Central

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring. PMID:28553167

Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

PubMed Central

Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

2014-01-01

Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring.

PubMed

Kiryanova, V; Meunier, S J; Vecchiarelli, H A; Hill, M N; Dyck, R H

2016-04-21

Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults. C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non-stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress (PS), perinatal Flx, PS and Flx, or neither PS or Flx, went through a comprehensive behavioral test battery. At the end of testing brain-derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring. Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive

Maternal Nutrition Induces Pervasive Gene Expression Changes but No Detectable DNA Methylation Differences in the Liver of Adult Offspring

PubMed Central

Cannon, Matthew V.; Buchner, David A.; Hester, James; Miller, Hadley; Sehayek, Ephraim; Nadeau, Joseph H.; Serre, David

2014-01-01

Aims Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize the phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic changes induced by maternal diet in adult offspring. Methods We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart. We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results Maternal diet had a significant effect on the body weight of the offspring when they were fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. We did not detect any effect of the maternal diet on DNA methylation in the liver. Conclusions Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver. PMID:24594983

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring.

PubMed

Sellayah, Dyan; Dib, Lea; Anthony, Frederick W; Watkins, Adam J; Fleming, Tom P; Hanson, Mark A; Cagampang, Felino R

2014-10-01

Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Female MF-1 mice were fed a normal protein (NP, 18% casein) or a protein-restricted (PR, 9% casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45% kcal fat) or standard chow (C, 7% kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7-11 per group). PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P < 0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P < 0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P < 0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.

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. Copyright © 2015. Published by Elsevier Inc.

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

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

Ao, Ying; Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071; Sun, Zhaoxia

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 asmore » 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

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

PubMed

Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

2012-12-17

Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

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.

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

Fish oil supplementation of rats during pregnancy reduces adult disease risks in their offspring.

PubMed

Joshi, Sadhana; Rao, Shobha; Golwilkar, Ajit; Patwardhan, Manisha; Bhonde, Ramesh

2003-10-01

Metabolic programming in utero due to maternal undernutrition is considered to increase the risk of adult diseases in offspring. It is therefore of relevance to investigate how dietary supplementation of specific nutrients can ameliorate the negative effects of maternal malnutrition. We examined the effects of supplementing fish oil or folic acid, both of which are conventional supplements in maternal intervention, on risk factors in the offspring as adults. Pregnant female rats from 4 groups (n = 6/group) were fed casein diets with 18 g/100 g protein (control diet), 12 g/100 g protein supplemented with 8 mg folic acid/kg diet (0.08 mg/kg diet) (FAS), 12 g/100 g protein without folic acid (FAD) or 12 g/100 g protein supplemented with 7 g/100 g fish oil (FOIL). Pups were weaned to a standard laboratory diet with 18 g/100 g protein. Serum glucose, insulin and cholesterol and plasma homocysteine levels were measured in the offspring at 6 and 11 mo of age. Serum glucose in 11-mo-old male and female pups was greater (P < 0.05) in both the FAS (males 2.46 +/- 0.51, females 2.49 +/- 0.29 mmol/L) and FAD groups (2.48 +/- 0.28 and 2.67 +/- 0.41 mmol/L) than in controls (2.03 +/- 0.15 and 2.02 +/- 0.18 mmol/L). Serum insulin concentrations were higher (P < 0.05) in the FAD group (males 1476 +/- 317, females 1441 +/- 220 pmol/L) but were lower in males from the FAS group (483 +/- 165 pmol/L) compared with controls (males 917 +/- 373, females 981 +/- 264 pmol/L). Glucose and insulin concentrations did not differ between the control and FOIL groups. Plasma homocysteine levels were lower (P < 0.05) only in 11-mo-old folate-deficient males; none of the other groups differed from the controls. Maternal supplementation of fish oil to a diet containing marginal protein was beneficial in maintaining circulating glucose, insulin, cholesterol and homocysteine levels in the offspring as adults.

Parental Involvement in Residential Care and Perceptions of their Offspring's Life Satisfaction in Residential Facilities for Adults with Intellectual Disability

ERIC Educational Resources Information Center

Schwartz, Chaya

2005-01-01

Background: This study examined parental involvement in relocation and post-placement care of offspring in residential facilities for adults with intellectual disability, as well as the characteristics of residents, parents, and residential institutions and the effect of those variables on parental perceptions of their offspring's life…

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

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

Wang, Lingxing; Cai, Ruowei; Lv, Guorong, E-mail: lxingwan502@gmail.com

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 maternalmore » 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.« less

Neck/upper back and low back pain in parents and their adult offspring: Family linkage data from the Norwegian HUNT Study.

PubMed

Lier, R; Nilsen, T I L; Vasseljen, O; Mork, P J

2015-07-01

Chronic pain in the neck and low back is highly prevalent. Although heritable components have been identified, knowledge about generational transmission of spinal pain between parents and their adult offspring is sparse. This study examined the intergenerational association of spinal pain using data from 11,081 parent-offspring trios participating in the population-based HUNT Study in Norway. Logistic regression was used to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for offspring spinal pain associated with parental spinal pain. In total, 3654 (33%) offspring reported spinal pain at participation. Maternal and paternal spinal pain was consistently associated with higher ORs for offspring spinal pain. The results suggest a slightly stronger association for parental multilevel spinal pain (i.e., both neck/upper back pain and low back pain) than for pain localized to the neck/upper back or low back. Multilevel spinal pain in both parents was associated with ORs of 2.6 (95% CI, 2.1-3.3), 2.4 (95% CI, 1.9-3.1) and 3.1 (95% CI, 2.2-4.4) for offspring neck/upper back, low back and multilevel spinal pain, respectively. Parental chronic spinal pain was consistently associated with increased occurrence of chronic spinal pain in their adult offspring, and this association was particularly strong for multilevel spinal pain. © 2014 European Pain Federation - EFIC®

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Depression or anxiety in adult twins is associated with asthma diagnosis but not with offspring asthma.

PubMed

Tedner, S G; Lundholm, C; Olsson, H; Almqvist, C

2016-06-01

Asthma is common in both children and adults in the Western world, just like anxiety and depression. While some research has revealed that these diseases might share important environmental and pathophysiological aspects, the exact mechanisms still remain unclear. To study the correlation firstly between depression or anxiety and asthma diagnosis in adult twins and secondly the association between parental depression or anxiety and offspring asthma in children of twins. In total, 24 685 adult twins aged 20-47 years were interviewed or completed a Web-based questionnaire and their children were identified through the Multi-Generation Register. Asthma diagnosis was obtained from the Patient Register and the Prescribed Drug Register. Assessment of depression and anxiety was obtained from questionnaires using Center for Epidemiologic Studies Depression Scale (CES-D), major depression and generalized anxiety disorder (GAD) from DSM-IV. The association between depression or anxiety and asthma was analyzed with logistic regression adjusting for confounders in twins and offspring. To address genetic and familial environmental confounding, we performed a cotwin analysis using disease-discordant twin pairs. We found an association between asthma and CES-D, major depression and GAD, for example adjusted OR for major depression and register-based asthma 1.56 (1.36-1.79). Most of the point estimates remained in the co-twin control analysis, indicating that the association was likely not due to genetic or familial environmental factors. There was no association between parental depression and/or anxiety and asthma diagnosis in the offspring which implies lack of genetic confounding. We found an association between own asthma diagnosis and anxiety or depression, but not with offspring asthma. Our results indicate that the associations were not due to confounding from genes or environment shared by the twins. © 2016 John Wiley & Sons Ltd.

Functional impairment due to bereavement after the death of adolescent or young adult offspring in a national population study of 1,051,515 parents.

PubMed

Wilcox, Holly C; Mittendorfer-Rutz, Ellenor; Kjeldgård, Linnea; Alexanderson, Kristina; Runeson, Bo

2015-08-01

This study addresses the burden of grief after the death of an adolescent or young adult offspring. Parental bereavement following the death of an adolescent or young adult offspring is associated with considerable psychiatric and somatic impairment. Our aim is to fill a research gap by examining offspring death due to suicide, accidents, or natural causes in relation to risk of parental sickness absence with psychiatric or somatic disorders. This whole population-based prospective study included mothers and fathers of all offspring aged 16-24 years in Sweden on December 31, 2004 (n = 1,051,515). This study had no loss to follow-up and exposure, confounders, and the outcome were recorded independently of each other. Cox survival analysis was used to model time to sickness absence exceeding 30 days, adjusting for parental demographic characteristics, previous parental sickness absence and disability pension, and inpatient and outpatient psychiatric and somatic healthcare prior to offspring death in 2001-2004. This large study population provided satisfactory statistical power for stratification by parents' sex and adolescent and young adults' cause of death. Mothers and fathers of offspring suicide and accident decedents both had over tenfold higher risk for psychiatric sickness absence exceeding 30 days as compared to parents of live offspring. Fathers of suicide decedents were at 40 % higher risk for somatic sickness absence. This is the largest study to date of parents who survived their offspring's death and the first study of work-related outcomes in bereaved parents. This study uses a broad metric of work-related functional impairment, sickness absence, for capturing the burden of sudden offspring death.

Perinatal nicotine exposure increases obesity susceptibility by peripheral leptin resistance in adult female rat offspring.

PubMed

Zhang, Wan-Xia; Li, Yin-Ping; Fan, Jie; Chen, Hui-Jian; Li, Gai-Ling; Ouyang, Yan-Qiong; Yan, You-E

2018-02-01

Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females. In adipose tissue and liver, the leptin signaling pathway was blocked at 26 weeks, presented lower Janus tyrosine kinase 2 and signal transducer and activator of transcription 3 gene expression, higher suppressor of cytokine signaling 3 gene expression (in adipose tissue) and lower leptin receptors gene expression (in liver), indicating that peripheral leptin resistance occurred in NIC-exposed adult females. In female rats, the expression of lipolysis genes was affected dominantly in adipose tissue, but lipogenesis genes was affected in liver. Furthermore, the glucose and insulin tolerance tests showed a delayed glucose clearance and a higher area under the curve in NIC-exposed females. Therefore, perinatal NIC exposure programed female rats for adipocyte hypertrophy and obesity in adult life, through the leptin resistance in peripheral tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Intergenerational Transmission of Resilience? Sense of Coherence Is Associated between Lithuanian Survivors of Political Violence and Their Adult Offspring.

PubMed

Kazlauskas, Evaldas; Gailiene, Danute; Vaskeliene, Ieva; Skeryte-Kazlauskiene, Monika

2017-01-01

Little is known about intergeneration effects on mental health in the families of survivors of political oppression of communist regime in Central and Eastern Europe. We aimed to explore post-traumatic stress in the second generation of the Lithuanian survivors of political violence, and analyze links between parental and adult offsprings' sense of coherence in the families exposed to political violence during the oppressive communist regime in Lithuania. A total of 110 matched pairs of communist regime political violence survivors (mean age = 73.22 years) and their adult offspring (mean age = 44.65 years) participated in this study. Life-time traumatic experiences and sense of coherence were measured in both parents and their offspring. Post-traumatic stress symptoms were assessed in the second generation of survivors. We found a high vulnerability in the second generation of the Lithuanian families of political violence survivors, with a 29% of probable PTSD in the second generation based on self-report measures. A significant positive correlation between parental and adult offsprings' sense of coherence was found. Post-traumatic stress symptoms were associated negatively with a sense of coherence in the second generation. Our study indicates the links between parental and the second generation's sense of coherence in the families of survivors of political violence. The study raises broader questions about the intergenerational aspects of resilience. Further studies are needed to explore the links between parental and child sense of coherence in other samples.

Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

PubMed

Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

2017-05-01

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O 3 ). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O 3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O 3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O 3 . Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O 3 with responses markedly exacerbated in males. HF diet and O 3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O 3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O 3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O 3 in their adult offspring in a sex-specific manner.

Affinity to host population stimulates physical growth in adult offspring of Turkish migrants in Germany.

PubMed

Özer, Aydan; Scheffler, Christiane

2018-06-11

Because of political conflicts and climate change, migration will be increased worldwide and integration in host societies is a challenge also for migrants. We hypothesize that migrants, who take up the challenge in a new social environment are taller than migrants who do not pose this challenge. We analyze by a questionnaire possible social, nutritional and ethnic influencing factors to body height (BH) of adult offspring of Turkish migrants (n = 82, 39 males) aged from 18 to 34 years (mean age 24.6 years). The results of multiple regression (downward selection) show that the more a male adult offspring of Turkish migrants feels like belonging to the Turkish culture, the smaller he is (95% CI, -3.79, -0.323). Further, the more a male adult offspring of Turkish migrants feels like belonging to the German culture, the taller he is (95% CI, -0.152, 1.738). We discussed it comparable to primates taking up their challenge in dominance, where as a result their body size increase is associated with higher IGF-1 level. IGF-1 is associated with emotional belonging and has a fundamental role in the regulation of metabolism and growth of the human body. With all pilot characteristics of our study results show that the successful challenge of integration in a new society is strongly associated with the emotional integration and identification in the sense of a personal sense of belonging to society. We discuss taller BH as a signal of social growth adjustment. In this sense, a secular trend of BH adaptation of migrants to hosts is a sign of integration.

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

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

Shen, Lang; Liu, Zhongfen; Gong, Jun

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 growthmore » 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

Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.

PubMed

Rajan, T V; Bailis, J M; Yates, J A; Shultz, L D; Greiner, D L; Nelson, F K

1994-12-01

We have used the severe combined immunodeficient C.B-17-scid/scid mouse to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infection with the human filarial parasite, Brugia malayi. C.B-17-scid/scid mice are permissive for infection while immunocompetent C.B-17(-)+/+ mice are uniformly resistant. Reciprocal matings of C.B-17-scid/scid and C.B-17(-)+/+ mice were performed. The C.B-17-scid/scid females were either naive or infected with Brugia malayi. The resulting immunocompetent C.B-17-scid/+ and C.B-17(-)+/scid progeny were challenged at weaning with an intraperitoneal injection of Brugia malayi third stage larvae known to produce patent infection in > 95% of C.B-17-scid/scid mice. We observed that 40.0%l (34/85) of the immunocompetent offspring of C.B-17-scid/scid females x C.B-17(-)+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was observed in susceptibility to infection between the progeny of infected or uninfected C.B-17-scid/scid mothers mated with C.B-17(-)+/+ fathers, arguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous progeny of wild type C.B-17(-)+/+ females mated with C.B-17-scid/scid males were permissive. These observations document conversion of a 'resistant' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offspring susceptibility to infection with Brugia malayi.

Educational Attainments of Immigrant Offspring: Success or Segmented Assimilation?

ERIC Educational Resources Information Center

Boyd, Monica

2002-01-01

Examined the educational attainments of adult offspring of immigrants age 20-64 years, analyzing data from Canada's 1996 Survey of Labour and Income Dynamics. Contrary to second generation decline and segmented underclass assimilation found in the United States, Canadian adult visible-minority immigrant offspring did not have lower educational…

Maternal high-protein diet during pregnancy, but not during suckling, induced altered expression of an increasing number of hepatic genes in adult mouse offspring.

PubMed

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

2016-04-01

Indirect effects of a high-protein maternal diet are not well understood. In this study, we analyzed short-term and sustainable effects of a prenatal versus early postnatal maternal high-protein diet on growth and hepatic gene expression in mouse offspring. Dams were exposed to an isoenergetic high-protein (HP, 40 % w/w) diet during pregnancy or lactation. Growth and hepatic expression profiles of male offspring were evaluated directly after weaning and 150 days after birth. Offspring from two dietary groups, high-protein diet during pregnancy and control diet during lactation (HPC), and control diet during pregnancy and high-protein diet during lactation (CHP), were compared with offspring (CC) from control-fed dams. Maternal CHP treatment was associated with sustained offspring growth retardation, but decreased numbers of affected hepatic genes in adults compared to weanlings. In contrast, offspring of the HPC group did not show persistent effects on growth parameters, but the number of affected hepatic genes was even increased at adult age. In both dietary groups, however, only a small subset of genes was affected in weanlings as well as in adults. We conclude that (1) prenatal and early postnatal maternal HP diet caused persistent, but (2) different effects and partially complementary trends on growth characteristics and on the hepatic transcriptome and associated pathways and that (3) only a small number of genes and associated upstream regulators might be involved in passing early diet-induced imprints to adulthood.

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

PubMed Central

Mahadevan, Sangeetha K.; Fiorotto, Marta L.; Van den Veyver, Ignatia B.

2017-01-01

Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP) or a control protein (20% protein, C) diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein) and single-housed until 8–12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration), depression (tail suspension and forced swim test), sociability (three-chamber), repetitive (marble burying), learning and memory (fear conditioning), and circadian behavior (wheel-running activity during light-dark and constant dark cycles). We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT). Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03), less energy expenditure (P = 0.004), less rearing activity (P = 0.04) and a greater number of night-time rest/sleep bouts (P = 0.03) compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01) but had no learning and memory deficit in fear-conditioning assay (P = 0.02). There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces

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

Parental history of moderate to severe infantile malnutrition is associated with cognitive deficits in their adult offspring.

PubMed

Waber, Deborah P; Bryce, Cyralene P; Girard, Jonathan M; Fischer, Laura K; Fitzmaurice, Garrett M; Galler, Janina R

2018-04-01

We compared the IQ and academic achievement of the young adult offspring of parents malnourished in infancy and those of a healthy control group in order to test the hypothesis that the offspring of previously malnourished individuals would show IQ and academic deficits that could be related to reduced parental socioeconomic status. We conducted a group comparison study based on a community sample in Barbados (Barbados Nutrition Study). Participants were adult children ≥16 years of age whose parents had been malnourished during the first year of life (n = 64; Mean age 19.3 years; 42% male) or whose parents were healthy community controls (n = 50; Mean age 19.7 years; 48% male). The primary outcome was estimated IQ (Wechsler Abbreviated Scale of Intelligence); a secondary outcome was academic achievement (Wide Range Achievement Test - Third Edition). Data were analyzed using PROC MIXED with and without adjusting for parental socioeconomic status (Hollingshead Index of Social Position). IQ was reduced in the offspring of previously malnourished parents relative to the offspring of controls (9.8 point deficit; P < 0.01), but this difference was not explained by parental socioeconomic status or parental IQ. The magnitude of the group difference was smaller for basic academic skills and did not meet criteria for statistical significance. The deleterious impact of infant malnutrition on cognitive function may be transmitted to the next generation; however, this intergenerational effect does not appear to be explained by the reduced socioeconomic status or IQ of the parent generation.

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 ...

Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring.

PubMed

Zhang, Yu-Ping; Huo, Yan-Li; Fang, Zhi-Qin; Wang, Xue-Fang; Li, Jian-Dong; Wang, Hai-Ping; Peng, Wei; Johnson, Alan Kim; Xue, Baojian

2018-05-01

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is

Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring.

PubMed

Pitsilis, George; Spyridakos, Dimitrios; Nomikos, George G; Panagis, George

2017-01-01

Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ 9 -tetrahydrocannabinol (Δ 9 -THC) induces transgenerational effects on the reward-facilitating effects of Δ 9 -THC and d -amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ 9 -THC (0.1 or 1 mg/kg, i.p.) or vehicle during postnatal days 28-50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ 9 -THC's (0, 0.1, 0.5, and 1 mg/kg, i.p.) and d -amphetamine's (0, 0.1, 0.5, and 1 mg/kg, i.p.) reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS) procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ 9 -THC was abolished in the F1 offspring of females that were exposed to Δ 9 -THC (0.1 or 1 mg/kg), whereas the reward-attenuating effect of the 1 mg dose of Δ 9 -THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d -amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ 9 -THC (1 mg/kg and 0.1 or 1 mg, respectively). The present results reveal that female Δ 9 -THC exposure during adolescence can diminish the reward-facilitating effects of Δ 9 -THC and d -amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ 9 -THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress.

PubMed

Cattani, Daiane; Cesconetto, Patrícia Acordi; Tavares, Mauren Kruger; Parisotto, Eduardo Benedetti; De Oliveira, Paulo Alexandre; Rieg, Carla Elise Heinz; Leite, Marina Concli; Prediger, Rui Daniel Schröder; Wendt, Nestor Cubas; Razzera, Guilherme; Filho, Danilo Wilhelm; Zamoner, Ariane

2017-07-15

We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats. The subchronic exposure to the pesticide decreased L-[ 14 C]-glutamate uptake and increased 45 Ca 2+ influx in 60-day-old rat hippocampus, suggesting a persistent glutamate excitotoxicity from developmental period (PND15) to adulthood (PND60). Moreover, GBH exposure alters the serum levels of the astrocytic protein S100B. The effects of GBH exposure were associated with oxidative stress and depressive-like behavior in offspring on PND60, as demonstrated by the prolonged immobility time and decreased time of climbing observed in forced swimming test. The mechanisms underlying the GBH-induced neurotoxicity involve the NMDA receptor activation, impairment of cholinergic transmission, astrocyte dysfunction, ERK1/2 overactivation, decreased p65 NF-κB phosphorylation, which are associated with oxidative stress and glutamate excitotoxicity. These neurochemical events may contribute, at least in part, to the depressive-like behavior observed in adult offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring.

PubMed

Bolton, Jessica L; Auten, Richard L; Bilbo, Staci D

2014-03-01

Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1β response to an LPS challenge at postnatal day (P)30, whereas their central IL-1β response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner. Copyright © 2013 Elsevier Inc. All rights reserved.

Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.

PubMed

Miyoshi, Jun; Bobe, Alexandria M; Miyoshi, Sawako; Huang, Yong; Hubert, Nathaniel; Delmont, Tom O; Eren, A Murat; Leone, Vanessa; Chang, Eugene B

2017-07-11

Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

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. (c) 2016 APA, all rights reserved.

Associations of Maternal Pre-Pregnancy Body Mass Index and Gestational Weight Gain with Adult Offspring Cardio-Metabolic Risk Factors: The Jerusalem Perinatal Family Follow-up Study

PubMed Central

Hochner, Hagit; Friedlander, Yechiel; Calderon-Margalit, Ronit; Meiner, Vardiella; Sagy, Yael; Avgil-Tsadok, Meytal; Burger, Ayala; Savitsky, Bella; Siscovick, David S.; Manor, Orly

2012-01-01

Background Accumulating evidence demonstrates that both maternal pre-pregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardio-metabolic risk factors in adulthood has not been comprehensively studied. Methods and Results We used a birth cohort of 1400 young adults born in Jerusalem, with extensive archival data as well as clinical information at age 32, to prospectively examine the associations of mppBMI and GWG with adiposity and related cardio-metabolic outcomes. Greater mppBMI, independent of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference (WC), systolic and diastolic BP, insulin and triglycerides and with lower HDL-C. For example, the effect sizes were translated to nearly 5kg/m2 higher mean BMI, 8.4cm higher WC, 0.13mmol/L (11.4mg/dL) higher triglycerides and 0.10mmol/L (3.8mg/dL) lower HDL-C among offspring of mothers within the upper mppBMI quartile (BMI>26.4kg/m2) compared to the lower (BMI<21.0kg/m2). GWG, independent of mppBMI, was positively associated with offspring adiposity; differences of 1.6kg/m2 in BMI and 2.4cm in waist were observed when offspring of mothers in the upper (GWG>14kg) and lower (GWG<9kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated to null the observed associations. Conclusions Maternal size both before and during pregnancy are associated with cardio-metabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardio-metabolic risk-reduction interventions. PMID:22344037

Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring1

PubMed Central

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.

2016-01-01

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

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...

Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.

PubMed

Strobl, Marie-Therese J; Freeman, Daniel; Patel, Jenica; Poulsen, Ryan; Wendler, Christopher C; Rivkees, Scott A; Coleman, Jason E

2017-05-01

Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats.

PubMed

Li, Min; Li, Xiaobai; Zhang, Xinxin; Ren, Jintao; Jiang, Han; Wang, Yan; Ma, Yuchao; Cheng, Wenwen

2014-06-01

Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection

PubMed Central

Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

2017-01-01

Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection with a large cohort of young adult participants (N = 257). Consistent with some previous human studies, we found that parental care in childhood alone had little association with the hippocampal volume in adulthood. However, when parental overprotection was low, parental care was positively correlated with offspring hippocampal volume, whereas there was no association between parental care and offspring hippocampal volume when parental overprotection was high. Thus, an interaction exists between parental care and overprotection in human’s hippocampal development, which contributes to the elucidation of the complex relationship between brain structure and environmental factors. PMID:28401913

Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection.

PubMed

Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

2017-04-12

Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection with a large cohort of young adult participants (N = 257). Consistent with some previous human studies, we found that parental care in childhood alone had little association with the hippocampal volume in adulthood. However, when parental overprotection was low, parental care was positively correlated with offspring hippocampal volume, whereas there was no association between parental care and offspring hippocampal volume when parental overprotection was high. Thus, an interaction exists between parental care and overprotection in human's hippocampal development, which contributes to the elucidation of the complex relationship between brain structure and environmental factors.

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

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…

The Transmission of Values to School-Age and Young Adult Offspring: Race and Gender Differences in Parenting

ERIC Educational Resources Information Center

Pagano, Maria E.; Hirsch, Barton J.; Deutsch, Nancy L.; McAdams, Dan P.

2003-01-01

The current study explores parental socialization practices and the values transmitted to school-aged and young adult off-spring, focusing on race and gender issues involved in parental teachings. A community sample of 187 black and white mothers and fathers were interviewed with regards to their parenting practices using both quantitative and…

Hyperglycaemia in pregnant rats causes sex-related vascular dysfunction in adult offspring: role of cyclooxygenase-2.

PubMed

de Sá, Francine Gomes; de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; da Silva, Odair Alves; Moreira, Hicla Stefany; Leal, Geórgia Andrade; da Rocha, Marcelo Aurélio; Duarte, Gloria Pinto; Xavier, Fabiano Elias

2017-08-01

What is the central question of this study? Hyperglycaemia during pregnancy induces vascular dysfunction and hypertension in male offspring. Given that female offspring from other fetal programming models are protected from the effects of fetal insult, the present study investigated whether there are sex differences in blood pressure and vascular function in hyperglycaemia-programmed offspring. What is the main finding and its importance? We demonstrated that hyperglycaemia in pregnant rats induced vascular dysfunction and hypertension only in male offspring. We found sex differences in oxidative stress and cyclooxygenase-2-derived prostanoid production that might underlie the vascular dysfunction. These differences, particularly in resistance arteries, may in part explain the absence of hypertension in female offspring born to hyperglycaemic dams. Exposure to maternal hyperglycaemia induces hypertension and vascular dysfunction in adult male offspring. Given that female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analysed possible differences relative to sex in blood pressure and vascular function in hyperglycaemia-programmed offspring. Hyperglycaemia was induced on day 7 of gestation (streptozotocin, 50 mg kg -1 ). Blood pressure, acetylcholine and phenylephrine or noradrenaline responses were analysed in the aorta and mesenteric resistance arteries of 3-, 6- and 12-month-old male and female offspring. Thromboxane A 2 release was analysed with commercial kits and superoxide anion (O 2 - ) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had higher blood pressure than control animals (O-CR). Contraction in response to phenylephrine increased and relaxation in response to acetylcholine decreased only in the aorta from 12-month-old male O-DR and not in age-matched O-CR. Contractile and vasodilator responses were preserved in both the

Parental longevity and offspring's home blood pressure: the Ohasama study.

PubMed

Watanabe, Yumiko; Metoki, Hirohito; Ohkubo, Takayoshi; Hirose, Takuo; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Hara, Azusa; Obara, Taku; Hoshi, Haruhisa; Totsune, Kazuhito; Imai, Yutaka

2010-02-01

Longevity is clustered in particular families. Some studies using conventional blood pressure (BP) reported an association between parental longevity and offspring's BP. No study has used self-measurement of BP at home (home BP). We examined the association between parental longevity and home BP values of adult Japanese offspring. Home and conventional BPs were measured in 1961 residents aged 40 years and over in the general population of Ohasama, Japan. Information about the ages of offspring's parents (age at death or current age) was obtained from a standardized questionnaire. The mean +/- SD values of systolic/diastolic home BP in offspring whose mothers died at less than 69 years of age, at 69-84 years of age, and in offspring whose mothers were alive at age 84 years were 127.4 +/- 13.2/76.2 +/- 9.1, 124.8 +/- 15.0/74.4 +/- 10.0, and 123.4 +/- 15.2/74.4 +/- 10.3 mmHg (P = 0.0002/0.009), respectively. Corresponding values in offspring whose fathers died at less than 66 years of age, at 66-80 years of age, and in offspring whose fathers were alive at age 80 years were 125.7 +/- 15.2/75.6 +/- 10.6, 124.7 +/- 14.1/75.0 +/- 9.2 and 122.4 +/- 14.6/73.6 +/- 9.5 mmHg (P = 0.001/0.003), respectively. Multivariate analysis demonstrated associations that were only weakly observed for conventional BP values (conventional BP: P = 0.3/0.4 for maternal and P = 0.3/0.3 for paternal longevity; home BP: P = 0.05/0.2 for maternal and P = 0.0004/0.007 for paternal longevity). Parental premature death was significantly associated with higher home BP levels in adult offspring, suggesting that parental longevity might be a useful additional marker for screening adult offspring at higher risk of hypertension.

Parental body mass index and blood pressure are associated with higher body mass index and blood pressure in their adult offspring: a cross-sectional study in a resource-limited setting in northern Peru.

PubMed

Carrillo-Larco, Rodrigo M; Bernabé-Ortiz, Antonio; Sal Y Rosas, Víctor G; Sacksteder, Katherine A; Diez-Canseco, Francisco; Cárdenas, María K; Gilman, Robert H; Miranda, J Jaime

2018-05-01

High body mass index (BMI) and blood pressure (BP) are major contributors to the high burden of non-communicable diseases in adulthood. Individual high-risk and population approaches for prevention require newer strategies to target these risk factors and focusing on the family to introduce prevention initiatives appears as a promising scenario. Characterisation of the relationship between BMI and BP among the adult members of a given family merits evaluation. We conducted a secondary analysis of an implementation study in Tumbes, Peru, benefiting from data derived from families with at least one adult offspring. The exposures of interest were the BMI, systolic BP (SBP) and diastolic BP (DBP) of the mother and father. The outcomes were the BMI, SBP and DBP of the offspring. Mixed-effects linear regression models were conducted. The mean age of the offspring, mothers and fathers was 29 (SD: 9.5), 54 (SD: 11.8) and 59 (SD: 11.6) years, respectively. Father's BMI was associated with a quarter-point increase in offspring BMI, regardless of the sex of the offspring. Mother's BMI had a similar effect on the BMI of her sons, but had no significant effect on her daughters'. Mother's SBP was associated with almost one-tenth of mmHg increase in the SBP of the adult offspring. There was no evidence of an association for DBP. In families with adult members, the higher the parents' BMI and SBP, the higher their adult offspring's levels will be. © 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

PubMed Central

McBride, Shawna M.; Culver, Bruce; Flynn, Francis W.

2008-01-01

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. PMID:18614766

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

Lin, Zhoumeng; Dodd, Celia A; Xiao, Shuo; Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M

2014-09-01

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. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

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

PubMed

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

Fetal exposure to hyperglycemia impacts negatively kidney development and function. 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. 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. 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. 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.

Later Life Impacts of Social Participation on Parents of Adult Offspring with and without Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Olsen, Darren L.

2018-01-01

Social participation is an important resource for parents in old age, and may be particularly important for parents living with adult offspring with intellectual and developmental disabilities. To evaluate whether socializing with friends and family and participating in social organizations protects against depression in old age, this study…

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...

(Meta)cognitive beliefs in posttraumatic stress disorder following forced displacement at the end of the Second World War in older adults and their offspring.

PubMed

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

2013-01-01

The aim of the present study was to investigate (meta)cognitive beliefs related to posttraumatic stress disorder (PTSD) in a sample of individuals displaced as children at the end of the Second World War as well as transgenerational effects of trauma and PTSD on the offspring. Displaced individuals with (n=20) and without PTSD (n=24) and nondisplaced healthy controls (n=11), as well as one of their adult offspring, were assessed with the Metacognitions Questionnaire (MCQ-30). Older adults, formerly displaced in childhood, were additionally assessed with the Posttraumatic Cognitions Inventory (PTCI). Dysfunctional beliefs (MCQ-30, PTCI) were particularly pronounced in formerly displaced individuals with PTSD, but not in the offspring generation. The findings suggest that in an aging group of displaced individuals with PTSD dysfunctional beliefs are associated with the disorder. Bias modification may help to attenuate symptomatology. No evidence was found for a transgenerational effect.

Parental Smoking and Adult Offspring's Smoking Behaviors in Ethnic Minority Groups: An Intergenerational Analysis in the HELIUS Study.

PubMed

Ikram, Umar Z; Snijder, Marieke B; Derks, Eske M; Peters, Ron J G; Kunst, Anton E; Stronks, Karien

2018-05-03

To understand smoking behaviors among ethnic minority groups, studies have largely focused on societal factors, with little attention to family influences. Yet studies among majority groups have identified parental smoking as an important risk factor. It is unknown whether this applies to ethnic minority groups. We investigated the association between parental smoking and adult offspring's smoking behaviors among ethnic minority groups with an immigrant background. We used data from the Healthy Life in an Urban Setting study from Amsterdam (the Netherlands) from January 2011 to December 2015. The sample consisted of 2184 parent-offspring pairs from South-Asian Surinamese, African Surinamese, Turkish, Moroccan, and Ghanaian origin. We collected self-reported smoking data: current status, duration of exposure to parental smoking, number of daily cigarettes, heavy smoking ( > 10 cigarettes/day), and nicotine dependency (using the Fagerström Test). Analyses were stratified by offspring's age, cohabitation with parent, education (parent/offspring), offspring's cultural orientation, and gender concordance within pairs. Logistic regression was used. Overall, parental smoking was associated with offspring's smoking behaviors (eg, current smoking: odds ratio 2.33; 95% confidence interval 1.79-3.03), with little ethnic variation. We found dose-response associations between exposure to parental smoking and offspring's smoking. The associations were similar across different strata but stronger in gender-concordant pairs (3.16; 2.12-4.51 vs. 1.73; 1.15-2.59 in gender-discordant pairs; p-value for interaction .017). Parental smoking is associated with offspring's smoking behaviors in ethnic minority groups across different strata but particularly in gender-concordant pairs. Similar to majority groups, family influences matter to smoking behaviors in ethnic minority groups. Our findings have deepened our understanding of smoking behaviors among ethnic minority groups. Future

Dysfunctional Cognitions among Offspring of Individuals with Bipolar Disorder.

PubMed

Ruggero, Camilo J; Bain, Kathleen M; Smith, Patrick M; Kilmer, Jared N

2015-07-01

Individuals with bipolar disorder often endorse dysfunctional beliefs consistent with cognitive models of bipolar disorder (Beck, 1976; Mansell, 2007). The present study sought to assess whether young adult offspring of those with bipolar disorder would also endorse these beliefs, independent of their own mood episode history. Participants (N = 89) were young adult college students with a parent with bipolar disorder (n = 27), major depressive disorder (MDD; n = 30), or no mood disorder (n = 32). Semi-structured interviews of the offspring were used to assess diagnoses. Dysfunctional beliefs related to Beck and colleagues' (2006) and Mansell's (2007) cognitive models were assessed. Unlike offspring of parents with MDD or no mood disorder, those with a parent with bipolar disorder endorsed significantly more dysfunctional cognitions associated with extreme appraisal of mood states, even after controlling for their own mood diagnosis. Once affected by a bipolar or depressive disorder, offspring endorsed dysfunctional cognitions across measures. Dysfunctional cognitions, particularly those related to appraisals of mood states and their potential consequences, are evident in young adults with a parent who has bipolar disorder and may represent targets for psychotherapeutic intervention.

Semen quality of young adult ICSI offspring: the first results.

PubMed

Belva, F; Bonduelle, M; Roelants, M; Michielsen, D; Van Steirteghem, A; Verheyen, G; Tournaye, H

2016-12-01

What is the semen quality of young adult men who were conceived 18-22 years ago by ICSI for male infertility? In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers. The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated. Since these children were conceived by ICSI because of severe male-factor infertility, there is reasonable concern that male offspring have inherited the deficient spermatogenesis from their fathers. Previously normal pubertal development and adequate Sertoli and Leydig cell function have been described in pubertal ICSI boys; however, no information on their sperm quality is currently available. This study was conducted at UZ Brussel between March 2013 and April 2016 and is part of a large follow-up project focussing on reproductive and metabolic health of young adults, between 18 and 22 years and conceived after ICSI with ejaculated sperm. Results of both a physical examination and semen analysis were compared between young ICSI men being part of a longitudinally followed cohort and spontaneously conceived controls who were recruited cross-sectionally. Results of a single semen sample in 54 young adult ICSI men and 57 spontaneously conceived men are reported. All young adults were individually assessed, and the results of their physical examination were completed by questionnaires. Data were analysed by multiple linear and logistic regression, adjusted for covariates. In addition, semen parameters of the ICSI fathers dating back from their ICSI treatment application were analysed for correlations. Young ICSI adults had a lower median sperm concentration (17.7 million/ml), lower median total sperm count (31.9 million) and lower median total motile sperm count (12.7 million) in comparison to spontaneously conceived peers (37.0 million/ml; 86

Preconception Alcohol Increases Offspring Vulnerability to Stress

PubMed Central

Jabbar, Shaima; Chastain, Lucy G; Gangisetty, Omkaram; Cabrera, Miguel A; Sochacki, Kamil; Sarkar, Dipak K

2016-01-01

The effect of preconception drinking by the mother on the life-long health outcomes of her children is not known, and therefore, in this study using an animal model, we determined the impact of preconception alcohol drinking of the mother on offspring stress response during adulthood. In our preconception alcohol exposure model, adult female rats were fed with 6.7% alcohol in their diet for 4 weeks, went without alcohol for 3 weeks and were bred to generate male and female offspring. Preconception alcohol-exposed offsprings' birth weight, body growth, stress response, anxiety-like behaviors, and changes in stress regulatory gene and protein hormone levels were evaluated. In addition, roles of epigenetic mechanisms in preconception alcohol effects were determined. Alcohol feeding three weeks prior to conception significantly affected pregnancy outcomes of female rats, with respect to delivery period and birth weight of offspring, without affecting maternal care behaviors. Preconception alcohol negatively affected offspring adult health, producing an increased stress hormone response to an immune challenge. In addition, preconception alcohol was associated with changes in expression and methylation profiles of stress regulatory genes in various brain areas. These changes in stress regulatory genes were normalized following treatment with a DNA methylation blocker during the postnatal period. These data highlight the novel possibility that preconception alcohol affects the inheritance of stress-related diseases possibly by epigenetic mechanisms. PMID:27296153

Elevated paternal glucocorticoid exposure modifies memory retention in female offspring.

PubMed

Yeshurun, Shlomo; Rogers, Jake; Short, Annabel K; Renoir, Thibault; Pang, Terence Y; Hannan, Anthony J

2017-09-01

Recent studies have demonstrated that behavioral traits are subject to transgenerational modification by paternal environmental factors. We previously reported on the transgenerational influences of increased paternal stress hormone levels on offspring anxiety and depression-related behaviors. Here, we investigated whether offspring sociability and cognition are also influenced by paternal stress. Adult C57BL/6J male mice were treated with corticosterone (CORT; 25mg/L) for four weeks prior to paired-matings to generate F1 offspring. Paternal CORT treatment was associated with decreased body weights of female offspring and a marked reduction of the male offspring. There were no differences in social behavior of adult F1 offspring in the three-chamber social interaction test. Despite male offspring of CORT-treated fathers displaying hyperactivity in the Y-maze, there was no observable difference in short-term spatial working memory. Spatial learning and memory testing in the Morris water maze revealed that female, but not male, F1 offspring of CORT-treated fathers had impaired memory retention. We used our recently developed methodology to analyze the spatial search strategy of the mice during the learning trials and determined that the impairment could not be attributed to underlying differences in search strategy. These results provide evidence for the impact of paternal corticosterone administration on offspring cognition and complement the cumulative knowledge of transgenerational epigenetic inheritance of acquired traits in rodents and humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal smoking during pregnancy and risk of alcohol use disorders among adult offspring.

PubMed

Nomura, Yoko; Gilman, Stephen E; Buka, Stephen L

2011-03-01

The aim of this study was to evaluate the association between maternal smoking during pregnancy (MSP) and lifetime risk for alcohol use disorder (AUD) and to explore possible mechanisms through which MSP may be related to neurobehavioral conditions during infancy and childhood, which could, in turn, lead to increased risk for AUD. A sample of 1,625 individuals was followed from pregnancy for more than 40 years. Capitalizing on the long follow-up time, we used survival analysis to examine lifetime risks of AUD (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) in relation to levels of MSP (none, <20 cigarettes/day, and ≥20 cigarettes/day). We then used structural equation modeling to test hypotheses regarding potential mechanisms, including lower birth weight, neurological abnormalities, poorer academic functioning, and behavioral dysregulation. Relative to unexposed offspring, offspring of mothers who smoked 20 cigarettes per day or more exhibited greater risks for AUD (hazard ratio = 1.31, 95% CI [1.08, 1.59]). However, no differences were observed among offspring exposed to fewer than 20 cigarettes per day. In structural equation models, MSP was associated with neurobehavioral problems during infancy and childhood, which, in turn, were associated with an increased risk for adult AUD. MSP was associated with an increased lifetime risk for AUD. Adverse consequences were evident from birth to adulthood. A two-pronged remedial intervention targeted at both the mother (to reduce smoking during pregnancy) and child (to improve academic functioning) may reduce the risk for subsequent AUD.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.

PubMed

Richgels, Phoebe K; Yamani, Amnah; Chougnet, Claire A; Lewkowich, Ian P

2017-11-01

Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. We sought to determine whether maternal HDM exposure influences asthma development in offspring. Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, T H 2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, T H 2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by

Mediators and moderators of parental alcoholism effects on offspring self-esteem.

PubMed

Rangarajan, Sripriya

2008-01-01

The goal of the proposed study was fourfold: (i) to examine the effects of parental alcoholism on adult offspring's self-esteem; (ii) to identify and test possible mediators and moderators of parental alcoholism effects on the self-esteem of adult offspring; (iii) to examine the utility and relevance of attachment theory (Bowlby J. (1969) Attachment and Loss: Vol. 1. Attachment. New York: Basic Books) in explaining parental alcoholism effects on self-esteem and (iv) to address some of the methodological limitations identified in past research on adult children of alcoholics (ACOA). Participants (N = 515) completed retrospective reports of parental alcoholism, family stressors, family communication patterns, parental attachment and a current measure of self-esteem. The results showed support for the detrimental effects of parental alcoholism on offspring self-esteem and offered partial support for family stressors as a mediator of parental alcoholism effects on parental attachment and parental attachment as a mediator of parental alcoholism effects on offspring self-esteem, respectively. Finally, support was found for family communication patterns as a moderator of the effects of family stressors on attachment. The study findings offer preliminary support for the utility of attachment theory in explicating parental alcoholism effects on the self-esteem of adult offspring. Findings from the present study make salient the need to consider factors beyond the identification of parental alcohol abuse when explicating individual differences in offspring self-esteem in adulthood. The identification of protective and risk factors can contribute to the development of optimal intervention strategies to help ACOAs better than simply the knowledge of family drinking patterns.

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring

PubMed Central

Wu, Wei-Li; Adams, Catherine E.; Stevens, Karen E.; Chow, Ke-Huan; Freedman, Robert; Patterson, Paul H.

2015-01-01

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal spleen-placenta-fetal brain axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (IL-6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of IL-6 in Chrna7 mutant mice. We found that the basal level of IL-6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7+/− offspring. The Chrna7+/− offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA. PMID:25683697

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring.

PubMed

Wu, Wei-Li; Adams, Catherine E; Stevens, Karen E; Chow, Ke-Huan; Freedman, Robert; Patterson, Paul H

2015-05-01

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal-placental-fetal axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (Il6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of Il6 in Chrna7 mutant mice. We found that the basal level of Il6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7(+/-) offspring. The Chrna7(+/-) offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA. Copyright © 2015 Elsevier Inc. All rights reserved.

Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats.

PubMed

Zhang, Xiaosong; Wang, Qi; Wang, Yan; Hu, Jingmin; Jiang, Han; Cheng, Wenwen; Ma, Yuchao; Liu, Mengxi; Sun, Anji; Zhang, Xinxin; Li, Xiaobai

2016-12-01

Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions

Tumors and proliferative lesions in adult offspring after maternal exposure to methylarsonous acid during gestation in CD1 mice.

PubMed

Tokar, Erik J; Diwan, Bhalchandra A; Thomas, David J; Waalkes, Michael P

2012-06-01

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 biological methylation of inorganic arsenic, could be a key carcinogenic species. Thus, pregnant CD1 mice were provided drinking water containing MMA3+ at 0 (control), 12.5, or 25 parts per million (ppm) from gestational days 8 to 18. Tumors were assessed in groups of male or female (initial n = 25) offspring up to 2 years of age. In utero treatment had no effect on survival or body weights. Female offspring exhibited increases in total epithelial uterine tumors (control 0%; 12.5 ppm 26%; 25 ppm 30%), oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%), adrenal cortical adenoma at 25 ppm (control 0%; 12.5 ppm 9%; 25 ppm 26%), and total epithelial ovarian tumors (control 0%; 12.5 ppm 39%; 25 ppm 26%). Male offspring showed dose-related increases in hepatocellular carcinoma (control 0%; 12.5 ppm 12%; 25 ppm 22%), adrenal adenoma (control 0%; 12.5 ppm 28%; 25 ppm 17%), and lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring had unusual testicular lesions, including two rete testis carcinomas, two adenomas, and three interstitial cell tumors. Overall, maternal consumption of MMA3+ during pregnancy in CD1 mice produced some similar proliferative lesions as gestationally applied inorganic arsenic in the offspring during adulthood.

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

PubMed Central

Tokar, Erik J.; Diwan, Bhalchandra A.; Thomas, David J.; Waalkes, Michael P.

2012-01-01

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 biological methylation of inorganic arsenic, could be a key carcinogenic species. Thus, pregnant CD1 mice were provided drinking water containing MMA3+ at 0 (control), 12.5 or 25 parts per million (ppm) from gestational day 8 to 18. Tumors were assessed in groups of male or female (initial n = 25) offspring up to two years of age. In utero treatment had no effect on survival or body weights. Female offspring exhibited increases in total epithelial uterine tumors (control 0%; 12.5 ppm 26%; 25 ppm 30%), oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%), adrenal cortical adenoma at 25 ppm (control 0%; 12.5 ppm 9%; 25 ppm 26%), and total epithelial ovarian tumors (control 0%; 12.5 ppm 39%; 25 ppm 26%). Male offspring showed dose-related increases in hepatocellular carcinoma (control 0%; 12.5 ppm 12%; 25 ppm 22%), adrenal adenoma (control 0%; 12.5 ppm 28%; 25 ppm 17%), and lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring had unusual testicular lesions, including two rete testis carcinomas and two adenomas, and three interstitial cell tumors. Overall, maternal consumption of MMA3+ during pregnancy in CD1 mice produced some similar proliferative lesions as gestationally applied inorganic arsenic in the offspring during adulthood. PMID:22398986

Prenatal Stress Disrupts Social Behavior, Cortical Neurobiology and Commensal Microbes in Adult Male Offspring.

PubMed

Gur, Tamar L; Palkar, Aditi Vadodkar; Rajasekera, Therese; Allen, Jacob; Niraula, Anzela; Godbout, Jonathan; Bailey, Michael T

2018-06-24

In utero and early neonatal exposure to maternal stress is linked with psychiatric disorders, and the underlying mechanisms are currently being elucidated. We used a prenatal stressor in pregnant mice to examine novel relationships between prenatal stress exposure, changes in the gut microbiome, and social behavior. Here, we show that males exposed to prenatal stress had a significant reduction in social behavior in adulthood, with increased corticosterone release following social interaction. Male offspring exposed to prenatal stress also had neuroinflammation, decreased oxytocin receptor, and decreased serotonin metabolism in their cortex in adulthood, which are linked to decreased social behavior. Finally, we found a significant difference in commensal microbes, including decreases in Bacteroides and Parabacteroides, in adult male offspring exposed to prenatal stress when compared to non-stressed controls. Our findings indicate that gestation is a critical window where maternal stress contributes to the development of aberrant social behaviors and alterations in cortical neurobiology, and that prenatal stress is sufficient to disrupt the male gut-brain axis into adulthood. Copyright © 2018. Published by Elsevier B.V.

Maternal depression in childhood and aggression in young adulthood: evidence for mediation by offspring amygdala-hippocampal volume ratio.

PubMed

Gilliam, Mary; Forbes, Erika E; Gianaros, Peter J; Erickson, Kirk I; Brennan, Lauretta M; Shaw, Daniel S

2015-10-01

There is abundant evidence that offspring of depressed mothers are at increased risk for persistent behavior problems related to emotion regulation, but the mechanisms by which offspring incur this risk are not entirely clear. Early adverse caregiving experiences have been associated with structural alterations in the amygdala and hippocampus, which parallel findings of cortical regions altered in adults with behavior problems related to emotion regulation. This study examined whether exposure to maternal depression during childhood might predict increased aggression and/or depression in early adulthood, and whether offspring amygdala:hippocampal volume ratio might mediate this relationship. Participants were 258 mothers and sons at socioeconomic risk for behavior problems. Sons' trajectories of exposure to maternal depression were generated from eight reports collected prospectively from offspring ages 18 months to 10 years. Offspring brain structure, aggression, and depression were assessed at age 20 (n = 170). Persistent, moderately high trajectories of maternal depression during childhood predicted increased aggression in adult offspring. In contrast, stable and very elevated trajectories of maternal depression during childhood predicted depression in adult offspring. Increased amygdala: hippocampal volume ratios at age 20 were significantly associated with concurrently increased aggression, but not depression, in adult offspring. Offspring amygdala: hippocampal volume ratio mediated the relationship found between trajectories of moderately elevated maternal depression during childhood and aggression in adult offspring. Alterations in the relative size of brain structures implicated in emotion regulation may be one mechanism by which offspring of depressed mothers incur increased risk for the development of aggression. © 2014 Association for Child and Adolescent Mental Health.

Maternal intake of trans-unsaturated or interesterified fatty acids during pregnancy and lactation modifies mitochondrial bioenergetics in the liver of adult offspring in mice.

PubMed

de Velasco, Patricia C; Chicaybam, Gustavo; Ramos-Filho, Dionizio M; Dos Santos, Raísa M A R; Mairink, Caroline; Sardinha, Fátima L C; El-Bacha, Tatiana; Galina, Antonio; Tavares-do-Carmo, Maria das Graças

2017-07-01

The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes for trans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich in trans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+ uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2 production was higher in the IG offspring. In addition, mitochondrial Ca2+ retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption of trans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.

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

PubMed

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

2015-04-10

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. © 2015 Authors.

Effects of nutritional supplementation during pregnancy on early adult disease risk: follow up of offspring of participants in a randomised controlled trial investigating effects of supplementation on infant birth weight.

PubMed

Macleod, John; Tang, Lie; Hobbs, F D Richard; Wharton, Brian; Holder, Roger; Hussain, Shakir; Nichols, Linda; Stewart, Paul; Clark, Penny; Luzio, Steve; Holly, Jeff; Smith, George Davey

2013-01-01

Observational evidence suggests that improving fetal growth may improve adult health. Experimental evidence from nutritional supplementation trials undertaken amongst pregnant women in the less developed world does not show strong or consistent effects on adult disease risk and no trials from the more developed world have previously been reported. To test the hypothesis that nutritional supplementation during pregnancy influences offspring disease risk in adulthood. Clinical assessment of a range of established diseases risk markers in young adult offspring of 283 South Asian mothers who participated in two trials of nutritional supplementation during pregnancy (protein/energy/vitamins; energy/vitamins or vitamins only) at Sorrento Maternity Hospital in Birmingham UK either unselected or selected on the basis of nutritional status. 236 (83%) offspring were traced and 118 (50%) of these were assessed in clinic. Protein/energy/vitamins supplementation amongst undernourished mothers was associated with increased infant birthweight. Nutritional supplementation showed no strong association with any one of a comprehensive range of markers of adult disease risk and no consistent pattern of association with risk across markers in offspring of either unselected or undernourished mothers. We found no evidence that nutritional supplements given to pregnant women are an important influence on adult disease risk however our study lacked power to estimate small effects. Our findings do not provide support for a policy of nutritional supplementation for pregnant women as an effective means to improve adult health in more developed societies.

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome

PubMed Central

Velazquez, Ramon; Ash, Jessica A.; Powers, Brian E.; Kelley, Christy M.; Strawderman, Myla; Luscher, Zoe I.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

2014-01-01

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer’s disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS. PMID:23643842

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. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Discrepancy in Reports of Support Exchanges between Parents and Adult Offspring: Within- and Between-Family Differences

PubMed Central

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

2014-01-01

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

Adrenocortical responses to offspring-directed threats in two open-nesting birds.

PubMed

Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

2009-07-01

Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

Evaluation of a Group Intervention to Assist Aging Parents with Permanency Planning for an Adult Offspring with Special Needs

ERIC Educational Resources Information Center

Botsford, Anne L.; Rule, David

2004-01-01

More than three-fourths of older adults with developmental disabilities and mental illness live in the community with aging parents, the majority of whom do not complete plans for the residential, financial, and legal future of their offspring. The authors used a true experimental design to evaluate the effectiveness of a six-week…

Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

PubMed

Gallant, S; Welch, L; Martone, P; Shalev, U

2017-06-15

Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

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. PsycINFO Database Record (c) 2014 APA, all rights reserved

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

Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood

PubMed Central

Krstew, Elena V.; Tait, Robert J.; Hulse, Gary K.

2012-01-01

Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero. PMID:23300784

Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats.

PubMed

Santos, Mery; Rodríguez-González, Guadalupe L; Ibáñez, Carlos; Vega, Claudia C; Nathanielsz, Peter W; Zambrano, Elena

2015-02-01

Exercise improves health but few data are available regarding benefits of exercise in offspring exposed to developmental programming. There is currently a worldwide epidemic of obesity. Obesity in pregnant women predisposes offspring to obesity. Maternal obesity has well documented effects on offspring reproduction. Few studies address ability of offspring exercise to reduce adverse outcomes. We observed increased oxidative stress and impaired sperm function in rat offspring of obese mothers. We hypothesized that regular offspring exercise reverses adverse effects of maternal obesity on offspring sperm quality and fertility. Female Wistar rats ate chow (C) or high-energy, obesogenic diet (MO) from weaning through lactation, bred at postnatal day (PND) 120, and ate their pregnancy diet until weaning. All offspring ate C diet from weaning. Five male offspring (different litters) ran on a wheel for 15 min, 5 times/week from PND 330 to 450 and were euthanized at PND 450. Average distance run per session was lower in MO offspring who had higher body weight, adiposity index, and gonadal fat and showed increases in testicular oxidative stress biomarkers. Sperm from MO offspring had reduced antioxidant enzyme activity, lower sperm quality, and fertility. Exercise in MO offspring decreased testicular oxidative stress, increased sperm antioxidant activity and sperm quality, and improved fertility. Exercise intervention has beneficial effects on adiposity index, gonadal fat, oxidative stress markers, sperm quality, and fertility. Thus regular physical exercise in male MO offspring recuperates key male reproductive functions even at advanced age: it's never too late. Copyright © 2015 the American Physiological Society.

Maternal peanut exposure during pregnancy and lactation reduces peanut allergy risk in offspring.

PubMed

López-Expósito, Iván; Song, Ying; Järvinen, Kirsi M; Srivastava, Kamal; Li, Xiu-Min

2009-11-01

Maternal allergy is believed to be a risk factor for peanut allergy (PNA) in children. However, there is no direct evidence of maternal transmission of PNA susceptibility, and it is unknown whether maternal peanut exposure affects the development of PNA in offspring. To investigate the influence of maternal PNA on offspring reactions to the first peanut exposure, and whether maternal low-dose peanut exposure during pregnancy and lactation influences these reactions and peanut sensitization in a murine model. Five-week-old offspring of PNA C3H/HeJ mothers (PNA-Ms) were challenged intragastrically with peanut (first exposure), and reactions were determined. In a subset of the experiment, PNA-Ms were fed a low dose of peanut (PNA-M/PN) or not fed peanut (PNA-M/none) during pregnancy and lactation. Their 5-week-old offspring were challenged intragastrically with peanut, and reactions were determined. In another subset of the experiment, offspring of PNA-M/PN or PNA-M/none were sensitized with peanut intragastrically for 6 weeks, and serum peanut-specific antibodies were determined. PNA-M offspring exhibited anaphylactic reactions at first exposure to peanut that were associated with peanut-specific IgG(1) levels and prevented by a platelet activation factor antagonist. In a subset experiment, PNA-M/PN offspring showed significantly reduced first-exposure peanut reactions, increased IgG(2a), and reduced mitogen-stimulated splenocyte cytokine production compared with PNA-M/none offspring. In an additional experiment, PNA-M/PN offspring showed reduction of peanut-specific IgE to active peanut sensitization. We show for the first time maternal transmission of susceptibility to first-exposure peanut reactions and active peanut sensitization. Low-dose peanut exposure during pregnancy and lactation reduced this risk.

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

Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring.

PubMed

Rossini, Kamila Fernanda; Oliveira, Camila Andrea de; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

2017-07-01

The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. A limitação dietética durante a gravidez influencia o crescimento e desenvolvimento do feto e da prole e sua saúde na vida adulta. Os mecanismos subjacentes dos efeitos adversos da restrição proteica gestacional (RPG) no desenvolvimento dos corações da prole não são bem compreendidos. Avaliar os efeitos da RPG sobre a estrutura cardíaca em filhotes machos de ratas aos 60 dias após o nascimento (d60). Ratos fêmeas Wistar grávidas foram alimentadas com uma dieta de proteína normal (PN, 17% caseína) ou de baixa proteína (BP, caseína 6%). Os valores de pressão arterial (PA) de descendentes do sexo masculino de

Parental and offspring associations of the metabolic syndrome in the Fels Longitudinal Study123

PubMed Central

Sabo, Roy T; Lu, Zheng; Deng, Xiaoyan; Ren, Chunfeng; Daniels, Stephen; Arslanian, Silva; Sun, Shumei S

2012-01-01

Background: Evidence shows that some causes of the metabolic syndrome (MS) begin in childhood, which could indicate a familial association, through either genetic inheritance or cohabitation. Objective: This study examined associations between parents and adult offspring diagnoses of the MS and its risk factors. Design: Measurements were obtained from adult participants and their adult offspring enrolled in the Fels Longitudinal Study, with simultaneous waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, HDL, and glucose observations used for diagnosis. On the basis of repeated measurements (in some cases), adult participants were classified as having the MS at least once or as never having the MS. Chi-square tests, ORs, and mixed-effects models were used to study familial associations. Results: Maternal (OR: 2.5; 95% CI: 1.1, 5.5) and paternal (OR: 4.1; 95% CI: 1.4, 12.1) MS classifications were significantly associated with MS classification in sons. MS classification in mothers and daughters (OR: 2.7; 95% CI: 0.9, 8.7; P = 0.08) was similar to that in sons but was not significant, whereas fathers and daughters were not associated (OR: 1.1; 95% CI: 0.4, 3.5). Maternal MS diagnoses were significantly and positively associated with triglycerides in male offspring and were significantly associated with SBP, DBP, and triglycerides in females. Paternal diagnoses were significantly associated only with DBP and HDL in male offspring. Conclusions: Parental MS diagnosis is significantly associated with MS diagnosis in adult male offspring, and adverse levels of certain risk factors are associated between offspring and parents, although these associations vary across risk factors and child sex. PMID:22811445

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome.

PubMed

Velazquez, Ramon; Ash, Jessica A; Powers, Brian E; Kelley, Christy M; Strawderman, Myla; Luscher, Zoe I; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2013-10-01

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer's disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota.

PubMed

Robertson, Ruairi C; Kaliannan, Kanakaraju; Strain, Conall R; Ross, R Paul; Stanton, Catherine; Kang, Jing X

2018-05-24

The early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes. Here, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in male murine offspring fed a high-fat diet. However, maternal fatty acid status appeared to have no significant effect on weight gain in female offspring. The metabolic phenotypes in male offspring appeared to be mediated by comprehensive restructuring of gut microbiota composition. Reduced maternal n-3 PUFA exposure led to significantly depleted Epsilonproteobacteria, Bacteroides, and Akkermansia and higher relative abundance of Clostridia. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than in utero. Furthermore, the maternal fatty acid profile appeared to have a long-lasting effect on offspring microbiota composition and function that persisted into adulthood after life-long high-fat diet feeding. Our data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by maternal fatty acid status through long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets, metabolic health, and the intestinal microbiome.

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

Salt intake during pregnancy alters offspring's myocardial structure.

PubMed

Alves-Rodrigues, E N; Veras, M M; Rosa, K T; de Castro, I; Furukawa, L N S; Oliveira, I B; Souza, R M; Heimann, J C

2013-05-01

To evaluate the effects of low or high salt intake during pregnancy on left ventricle of adult male offspring. Low- (LS, 0.15%), normal- (NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to Wistar rats during pregnancy. During lactation all dams received NS as well as the offspring after weaning. To evaluate cardiac response to salt overload, 50% of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean blood pressure (MBP), histology and left ventricular angiotensin II content (AII) were analyzed at 36 weeks of age. Interventricular septum, left ventricular posterior wall and relative wall thickness increased from the 20th to the 30th week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared to NShs, LShs and HSns. AII and left ventricular fibrosis were not different among groups. HS during pregnancy programs adult male offspring to a blood pressure and angiotensin II independent concentric left ventricular hypertrophy, with no fibrosis, in response to a chronic high-salt intake. Copyright © 2011 Elsevier B.V. All rights reserved.

Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring.

PubMed

Lacy, Ryan T; Brown, Russell W; Morgan, Amanda J; Mactutus, Charles F; Harrod, Steven B

2016-01-01

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth weight in offspring, but it can also negatively influence neurodevelopmental outcomes in later stages of life, such as an increased incidence of obesity and drug abuse. Animal models demonstrate that prenatal nicotine (PN) alters the development of the mesocorticolimbic system, which is important for organizing goal-directed behavior. In the present study, we determined whether intravenous (IV) PN altered the initiation and/or expression of methamphetamine (METH)-induced locomotor sensitization as a measure of mesocorticolimbic function in adult rat offspring. We also determined whether PN and/or METH exposure altered protein levels of BDNF (brain-derived neurotrophic factor) in the nucleus accumbens, the dorsal striatum, and the prefrontal cortex of adult offspring. BDNF was of interest because of its role in the development and maintenance of the mesocorticolimbic pathway and its ability to modulate neural processes that contribute to drug abuse, such as sensitization of the dopamine system. Dams were injected with IV nicotine (0.05 mg/kg/injection) or saline, 3×/day on gestational days 8-21. Testing was conducted when offspring reached adulthood (around postnatal day 90). Following 3 once daily habituation sessions the animals received a saline injection and baseline locomotor activity was measured. PN and prenatal saline (PS)-exposed offspring then received 10 once daily injections of METH (0.3 mg/kg) to induce locomotor sensitization. The animals received a METH injection (0.3 mg/kg) to assess the expression of sensitization following a 14-day period of no injections. A day later, all animals were injected with saline and conditioned hyperactivity was assessed. Brain tissue was harvested 24 h later. PN animals habituated more slowly to the activity chambers

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)

A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

PubMed

Cuthbert, Candace E; Foster, Jerome E; Ramdath, D Dan

2017-10-01

A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (P<0·05) of genes coding for v-Akt murine thymoma viral oncogene homolog 2, resistin and v-Raf-1 murine leukaemia viral oncogene homolog 1 (Raf1) in offspring skeletal muscle and acetyl-CoA carboxylase (Acaca), fatty acid synthase and phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit β in offspring liver. Skeletal muscle neuropeptide Y and hepatic Kruppel-like factor 10 were up-regulated in HFS v. CON offspring (P<0·05). Compared with CON, Acaca and Raf1 protein expression levels were significantly lower in HFS offspring. Maternal HFS induced higher homoeostasis model of assessment index of insulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment

PubMed Central

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

2014-01-01

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

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. © The Author(s) 2015.

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

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

Exposure of Pregnant Mice to Perfluorobutanesulfonate Causes Hypothyroxinemia and Developmental Abnormalities in Female Offspring.

PubMed

Feng, Xuejiao; Cao, Xinyuan; Zhao, Shasha; Wang, Xiaoli; Hua, Xu; Chen, Lin; Chen, Ling

2017-02-01

Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence of prenatal PFBS exposure on perinatal growth and development, pubertal onset, and reproductive and thyroid endocrine system in female mice. Here, we show that when PFBS (200 and 500 mg/kg/day) was orally administered to pregnant mice (PFBS-dams) on days 1-20 of gestation; their female offspring (PFBS-offspring) exhibited decreased perinatal body weight and delayed eye opening compared with control offspring. Vaginal opening and first estrus were also significantly delayed in PFBS-offspring, and diestrus was prolonged. Ovarian and uterine size, as well as follicle and corpus luteum numbers, were reduced in adult PFBS-offspring. Furthermore, pubertal and adult PFBS-offspring exhibited decreases in serum estrogen (E2) and progesterone (P4) levels with the elevation of luteinizing hormone levels. Notably, decreases in serum total thyroxine (T4) and 3,3', 5-triiodothyronine (T3) levels were observed in fetal, pubertal, and adult PFBS-offspring in conjunction with slight increases in thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone levels. In addition, PFBS-dams exhibited significant decreases in total T4 and T3 levels and free T4 levels and increases in TSH levels, but no changes in E2 and P4 levels. These results indicate that prenatal PFBS exposure (≥200 mg/kg/day) causes permanent hypothyroxinemia accompanied by deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Early Life Exposure to Undernutrition Induces ER Stress, Apoptosis, and Reduced Vascularization in Ovaries of Adult Rat Offspring1

PubMed Central

Chan, Kaitlyn A.; Bernal, Angelica B.; Vickers, Mark H.; Gohir, Wajiha; Petrik, Jim J.; Sloboda, Deborah M.

2015-01-01

ABSTRACT Maternal nutritional restriction has been shown to induce impairments in a number of organ systems including the ovary. We have previously shown that maternal undernutrition induces fetal growth restriction and low birth weight, and results in an offspring ovarian phenotype characteristic of premature ovarian aging with reduced ovarian reserve. In the present study, we set out to investigate the underlying mechanisms that lead offspring of undernourished mothers to premature ovarian aging. Pregnant dams were randomized to 1) a standard diet throughout pregnancy and lactation (control), 2) a calorie-restricted (50% of control) diet during pregnancy, 3) a calorie-restricted (50% of control) diet during pregnancy and lactation, or 4) a calorie-restricted (50% of control) diet during lactation alone. The present study shows that early life undernutrition-induced reduction of adult ovarian follicles may be mediated by increased ovarian endoplasmic reticulum stress in a manner that increased follicular apoptosis but not autophagy. These changes were associated with a loss of ovarian vessel density and are consistent with an accelerated ovarian aging phenotype. Whether these changes are mediated specifically by a reduction in the local antioxidant environment is unclear, although our data suggest the possibility that ovarian melatonin may play a part in early life nutritional undernutrition and impaired offspring folliculogenesis. PMID:25810471

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.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Contextual risks linking parents’ adolescent marijuana use to offspring onset

PubMed Central

Kerr, David C. R.; Tiberio, Stacey S.; Capaldi, Deborah M.

2015-01-01

Objective We studied the extent to which parent marijuana use in adolescence is associated with marijuana use onset in offspring through contextual family and peer risks. Method Fathers assessed (n = 93) since childhood, their 146 offspring (n = 83 girls), and offspring's mothers (n = 85) participated in a longitudinal study. Using discrete-time survival analysis, fathers’ (prospectively measured) and mothers’ (retrospective) adolescent marijuana use was used to predict offspring marijuana use onset through age 19 years. Parental monitoring, child exposure to marijuana use, peer deviance, peer marijuana use, and perceptions of parent disapproval of child use were measured before or concurrent with onset. Results Parents’ adolescent marijuana use was significantly associated with less monitoring, offspring alcohol use, the peer behaviors, exposure to adult marijuana use, and perceptions of less parent disapproval. Male gender and the two peer behaviors were positively associated with children's marijuana use onset, controlling for their alcohol use. Parents’ adolescent marijuana use had a significant indirect effect on child onset through children's deviant peer affiliations and a composite contextual risk score. Conclusions Parents’ histories of marijuana use may contribute indirectly to children's marijuana use onset through their influence on the social environments children encounter; specifically, those characterized by more liberal use norms, exposure to marijuana use and deviant and marijuana-using peers, and less adult supervision. Given that alcohol use onset was controlled, findings suggest that the contextual factors identified here confer unique risk for child marijuana use onset. PMID:26166667

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

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

PubMed

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.

Filial anxiety and sense of obligation among offspring of Holocaust survivors.

PubMed

Shrira, Amit; Menashe, Ravit; Bensimon, Moshe

2018-03-13

Much is known about adult children caring for their aging parents, yet the potentially unique experience of offspring caring for traumatized parents is underexplored. Therefore, the current studies assessed filial anxiety and sense of obligation among offspring of Holocaust survivors (OHS) in caring for their parents. In Study 1, we interviewed 10 OHS (mean age = 61.0) in order to extract themes of filial anxiety. Based on Study 1's data, a newly constructed scale of filial anxiety was administered in Study 2 to 59 adult offspring (mean age = 56.4): 28 OHS and 31 comparisons. Study 3 included 143 dyads of parents and offspring (mean age = 55.4 and 81.7, respectively): 86 Holocaust dyads and 57 comparison dyads. Parents reported posttraumatic stress disorder (PTSD) symptoms and offspring reported filial anxiety and sense of obligation. In Study 1, interviewees referred to concerns about parent experiencing decline alongside caregiving difficulties. In Study 2, OHS reported higher filial anxiety and sense of obligation relative to comparisons. This group difference was mediated by sense of obligation. In Study 3, OHS with parental PTSD reported higher filial anxiety and sense of obligation relative to comparisons. Once more, filial sense of obligation served as a mediator. In Studies 2-3, results remained significant after adjusting for offspring symptoms. Parental exposure to the Holocaust, and especially parental PTSD, related to higher filial obligation, which in turn was related to higher filial anxiety. These findings bear important implications for practitioners working with survivors' families.

Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring? A prospective study over two decades.

PubMed

Danielsen, Inge; Granström, Charlotta; Rytter, Dorte; Hammer Bech, Bodil; Brink Henriksen, Tine; Vaag, Allan Arthur; Olsen, Sjurdur Frodi

2013-08-01

It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring. Longitudinal study where 965 pregnant women during 1988-1989 had four dimensions of PA assessed by questionnaires in gestation week 30: PA at work; leisure time PA, daily amount of walking-biking and sport participation. The following MS markers were assessed in the offspring (n=439): body mass index (BMI), waist circumference, blood pressure, homeostasis model assessment insulin resistance as well as fasting plasma glucose, triglycerides, cholesterol (high-density lipoprotein (HDL), low-density lipoprotein and total cholesterol), insulin and leptin levels. Walking-biking PA in pregnancy is associated with unchanged or subtle, adverse changes of distinct MS markers among offspring including lower levels of HDL cholesterol (ratio 0.95 (95% CI 0.92 to 0.98) per 1 h increment in walking-biking), a higher diastolic blood pressure (difference 1.12 (95% CI 0.03 to 2.20) mm Hg/1 h increment) and a higher BMI (ratio 1.03 (95% CI 1.01 to 1.05) per 1 h increment). In separate analyses in males, these associations persisted and additional adverse associations were found for triglycerides, systolic blood pressure, waist circumference and leptin. No associations were detected with other measures of PA. The study did not substantiate any protective effects of PA in pregnancy. In contrast, data suggested that high amounts of daily walking-biking in pregnancy may have adverse effects on levels of HDL cholesterol, diastolic blood pressure and BMI in young adult offspring.

Parental Legacy in Insects: Variation of Transgenerational Immune Priming during Offspring Development

PubMed Central

Trauer, Ute; Hilker, Monika

2013-01-01

In insects, a parental immune challenge can prepare and enhance offspring immune activity. Previous studies of such transgenerational immune priming (TGIP) mainly focused on a single offspring life stage. However, different developmental stages may be exposed to different risks and show different susceptibility to parental immune priming. Here we addressed the question (i) whether TGIP effects on the immunity of Manduca sexta offspring vary among the different developmental offspring stages. We differentiated between unchallenged and immunochallenged offspring; for the latter type of offspring, we further investigated (ii) whether TGIP has an impact on the time that enhanced immune levels persist after offspring immune challenge. Finally, we determined (iii) whether TGIP effects on offspring performance depend on the offspring stage. Our results show that TGIP effects on phenoloxidase (PO) activity, but not on antibacterial activity, vary among unchallenged offspring stages. In contrast, TGIP effects on PO and antibacterial activity did not vary among immunochallenged offspring stages. The persistence of enhanced immune levels in immunochallenged offspring was dependent on the parental immune state. Antibacterial (but not PO) activity in offspring of immunochallenged parents decreased over five days after pupal immune challenge, whereas no significant change over time was detectable in offspring of control parents. Finally, TGIP effects on the developmental time of unchallenged offspring varied among stages; young larvae of immunochallenged parents developed faster and gained more weight than larvae of control parents. However, offspring females of immunochallenged parents laid fewer eggs than females derived from control parents. These findings suggest that the benefits which the offspring gains from TGIP during juvenile development are paid by the adults with reduced reproductive power. Our study shows that TGIP effects vary among offspring stages and depend on

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

USDA-ARS?s Scientific Manuscript database

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...

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

Parental exposure to heavy fuel oil induces developmental toxicity in offspring of the sea urchin Strongylocentrotus intermedius.

PubMed

Duan, Meina; Xiong, Deqi; Yang, Mengye; Xiong, Yijun; Ding, Guanghui

2018-05-03

The present study investigated the toxic effects of parental (maternal/paternal) exposure to heavy fuel oil (HFO) on the adult reproductive state, gamete quality and development of the offspring of the sea urchin Strongylocentrotus intermedius. Adult sea urchins were exposed to effluents from HFO-oiled gravel columns for 7 days to simulate an oil-contaminated gravel shore, and then gametes of adult sea urchins were used to produce embryos to determine developmental toxicity. For adult sea urchins, no significant difference in the somatic size and weight was found between the various oil loadings tested, while the gonad weight and gonad index were significantly decreased at higher oil loadings. The spawning ability of adults and fecundity of females significantly decreased. For gametes, no effect was observed on the egg size and fertilization success in any of the groups. However, a significant increase in the percentage of anomalies in the offspring was observed and then quantified by an integrative toxicity index (ITI) at 24 and 48 h post fertilization. The offspring from exposed parents showed higher ITI values with more malformed embryos. The results confirmed that parental exposure to HFO can cause adverse effects on the offspring and consequently affect the recruitment and population maintenance of sea urchins. Copyright © 2018 Elsevier Inc. All rights reserved.

A Children of Twins Study of parental divorce and offspring psychopathology

PubMed Central

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Maes, Hermine H.; Silberg, Judy; Eaves, Lindon J.

2010-01-01

Background Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. Method We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. Results The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. Conclusions The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed. PMID:17593147

A Children of Twins Study of parental divorce and offspring psychopathology.

PubMed

D'Onofrio, Brian M; Turkheimer, Eric; Emery, Robert E; Maes, Hermine H; Silberg, Judy; Eaves, Lindon J

2007-07-01

Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed.

Age at Onset of Type 1 Diabetes in Parents and Recurrence Risk in Offspring

PubMed Central

Harjutsalo, Valma; Lammi, Niina; Karvonen, Marjatta; Groop, Per-Henrik

2010-01-01

OBJECTIVE Our aim was to study the recurrence risk of type 1 diabetes in the offspring of parents with adult-onset (15–39 years) type 1 diabetes and to evaluate the transmission of diabetes within a continuum of parental age at onset of diabetes from childhood to adulthood. RESEARCH DESIGN AND METHODS Diabetes status of all offspring (n = 9,636) in two Finnish cohorts of parents with type 1 diabetes was defined until the end of year 2007. Cumulative incidences of type 1 diabetes among the offspring were estimated, and several factors contributing to the risk were assessed. RESULTS During 137,455 person-years, a total of 413 offspring were diagnosed with type 1 diabetes. The cumulative incidence by 20 years was 4.0% (95% CI 3.1–4.8) for the offspring of parents with adult-onset diabetes. The risk was equal according to the sex of the parents. The cumulative incidence decreased in parallel with the increase in age at onset of diabetes in the fathers. In the offspring of diabetic mothers, the risk was equal regardless of the age at onset of diabetes. However, the reduced risk in the maternal offspring was most pronounced in the daughters of the mothers with a diagnosis age <10 years. CONCLUSIONS Type 1 diabetes transmission ratio distortion is strongly related to the sex and age at onset of diabetes in the diabetic parents. PMID:19833881

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

PubMed

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

2015-11-02

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. Cross-sectional general population survey. Scotland. 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. 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. 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/m(2). 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. There are modest genetic/epigenetic influences on the environmental factors behind adverse

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.

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

Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity.

PubMed

Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J

2017-03-31

Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues.

Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

PubMed Central

Cissé, Yasmine M.; Russart, Kathryn L.G.; Nelson, Randy J.

2017-01-01

Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues. PMID:28361901

Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.

PubMed

Latouche, Celine; Heywood, Sarah E; Henry, Sarah L; Ziemann, Mark; Lazarus, Ross; El-Osta, Assam; Armitage, James A; Kingwell, Bronwyn A

2014-03-01

Children of obese mothers have increased risk of metabolic syndrome as adults. Here we report the effects of a high-fat diet in the absence of maternal obesity at conception on skeletal muscle metabolic and transcriptional profiles of adult male offspring. Female Sprague Dawley rats were fed a diet rich in saturated fat and sucrose [high-fat diet (HFD): 23.5% total fat, 9.83% saturated fat, 20% sucrose wt:wt] or a normal control diet [(CD) 7% total fat, 0.5% saturated fat, 10% sucrose wt:wt] for the 3 wk prior to mating and throughout pregnancy and lactation. Maternal weights were not different at conception; however, HFD-fed dams were 22% heavier than controls during pregnancy. On a normal diet, the male offspring of HFD-fed dams were not heavier than controls but demonstrated features of insulin resistance, including elevated plasma insulin concentration [40.1 ± 2.5 (CD) vs 56.2 ± 6.1 (HFD) mU/L; P = 0.023]. Next-generation mRNA sequencing was used to identify differentially expressed genes in the offspring soleus muscle, and gene set enrichment analysis (GSEA) was used to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 upregulated pathways, including cytokine signaling (P < 0.005), starch and sucrose metabolism (P < 0.017), inflammatory response (P < 0.024), and cytokine-cytokine receptor interaction (P < 0.037). A further 8 pathways were downregulated, including oxidative phosphorylation (P < 0.004), mitochondrial matrix (P < 0.006), and electron transport/uncoupling (P < 0.022). Phosphorylation of the insulin signaling protein kinase B was reduced [2.86 ± 0.63 (CD) vs 1.02 ± 0.27 (HFD); P = 0.027] and mitochondrial complexes I, II, and V protein were downregulated by 50-68% (P < 0.005). On a normal diet, the male offspring of HFD-fed dams did not become obese adults but developed insulin resistance, with transcriptional evidence of muscle cytokine activation, inflammation, and mitochondrial dysfunction. These

A Maternal Low-Fiber Diet Predisposes Offspring to Improved Metabolic Phenotypes in Adulthood in an Herbivorous Rodent.

PubMed

Zhang, Xue-Ying; Lou, Mei-Fang; Shen, Wei; Fu, Rong-Shu; Wang, De-Hua

The maternal or paternal dietary composition can have important effects on various aspects of their offspring's physiology. Studies from animal models and humans showed that a maternal high-fiber diet protected offspring against fat accumulation. However, little is known about how a maternal low-fiber diet modifies the metabolism of offspring in herbivorous rodents. We hypothesized that a maternal low-fiber diet would confer long-lasting beneficial effects on offspring metabolic phenotypes in herbivorous Brandt's vole (Lasiopodomys brandtii). Female voles were fed either a control (12.4% fiber) or a low-fiber (3.5% fiber) diet throughout pregnancy and lactation, and all offspring were fed the control diet after weaning till 14 wk old. Offspring were sampled from each litter at 18 d and 14 wk of age. Another subset of adult offspring at 15 wk of age was fed a high-fat diet for 8 wk. We found that there was no difference in litter size, litter mass, or pup mass before weaning between the two maternal diet groups. Offspring from the maternal low-fiber diet increased energy intake, body mass, and lean mass; suppressed fat accumulation; and improved glucose tolerance compared with those from the control diet. Moreover, the maternal low-fiber diet alleviated high-fat diet-induced obesity in the adult offspring. Serum leptin concentration and uncoupling protein 1 content in brown adipose tissue of offspring were not affected by a maternal low-fiber diet. We demonstrate that herbivorous females fed a low-fiber diet during pregnancy and lactation may predispose their offspring to accelerated growth of lean tissue, which may increase the opportunity for survival and reproduction in offspring.

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 Central

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

2009-01-01

Consuming omega-3 fatty acids (ω-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 ω-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 ω-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 ω-3 FA condition (ω-3/ω-6 ratio ~ 0.14), the Excess ω-3 FA condition (ω-3/ω-6 ratio ~ 14.0) and Deficient ω-3 FA condition (ω-3/ω-6 ratio ~ 0% ratio). The Control diet contained 7 % soybean oil; whereas the Deficient and Excess ω-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 Control group in response to the 8 kHz tone pips only. The Excess group

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).…

Adult murine CNS stem cells express aquaporin channels.

PubMed

La Porta, Caterina A M; Gena, Patrizia; Gritti, Angela; Fascio, Umberto; Svelto, Maria; Calamita, Giuseppe

2006-02-01

Fluid homoeostasis is of critical importance in many functions of the CNS (central nervous system) as indicated by the fact that dysregulation of cell volume underlies clinical conditions such as brain oedema and hypoxia. Water balance is also important during neurogenesis as neural stem cells move considerable amounts of water into or out of the cell to rapidly change their volume during differentiation. Consistent with the relevance of water transport in CNS, multiple AQP (aquaporin) water channels have been recognized and partially characterized in brain cell function. However, the presence and distribution of AQPs in CNS stem cells has not yet been assessed. In the present study, we investigate the expression and subcellular localization of AQPs in murine ANSCs (adult neural stem cells). Considerable AQP8 mRNAs were found in ANSCs where, as expected, the transcript of two additional AQPs, AQP4 and AQP9, was also detected. Immunoblotting with subcellular membrane fractions of ANSCs showed predominant expression of AQP8 in the mitochondria-enriched fraction. This result was consistent with the spotted immunoreactivity profile encountered within the ANSCs by confocal immunofluorescence. AQP8 may have a role in mitochondrial volume regulation during ANSC differentiation. Recognition of AQPs in ANSCs is a step forward in our knowledge of water homoeostasis in the CNS and provides useful information for the purposes of stem cell technology.

Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring

PubMed Central

Ramírez-López, María Teresa; Arco, Raquel; Decara, Juan; Vázquez, Mariam; Noemí Blanco, Rosario; Alén, Francisco; Suárez, Juan; Gómez de Heras, Raquel

2016-01-01

Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS). In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a) the adult expression of endocannabinoid-related behaviors, b) the metabolic profile of adult offspring and c) the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a) sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b) features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c) tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed. PMID:27806128

Grandparentage assignments identify unexpected adfluvial life history tactic contributing offspring to a reintroduced population.

PubMed

Sard, Nicholas M; Jacobson, Dave P; Banks, Michael A

2016-10-01

Diversity in life history tactics contributes to the persistence of a population because it helps to protect against stochastic environments by varying individuals in space and time. However, some life history tactics may not be accounted for when assessing the demographic viability of a population. One important factor in demographic viability assessments is cohort replacement rate (CRR), which is defined as the number of future adults produced by an adult. We assessed if precocial resident males (adults that reside in freshwater their entire lives, contributed offspring to a reintroduced population from 2008 to 2013. We found that 9 ± 5% of offspring with an unassigned parent remained unexplained after accounting for sources of human error. Using grandparentage assignments, we identified 31 precocial resident males and 48 probable adfluvial Chinook salmon produced by anadromous mate pairs from 2007 to 2012. Previously published CRR estimates for the 2007 and 2008 reintroduced adults, based on only anadromous returning adult offspring, were 0.40 and 0.31, respectively. By incorporating adfluvial females, we found CRR estimates increased by 17% (CRR: 0.46) and 13% (CRR: 0.35) for the 2007 and 2008 cohorts, respectively.

A test of maternal programming of offspring stress response to predation risk in threespine sticklebacks.

PubMed

Mommer, Brett C; Bell, Alison M

2013-10-02

Non-genetic maternal effects are widespread across taxa and challenge our traditional understanding of inheritance. Maternal experience with predators, for example, can have lifelong consequences for offspring traits, including fitness. Previous work in threespine sticklebacks showed that females exposed to simulated predation risk produced eggs with higher cortisol content and offspring with altered anti-predator behavior. However, it is unknown whether this maternal effect is mediated via the offspring glucocorticoid stress response and if it is retained over the entire lifetime of offspring. Therefore, we tested the hypothesis that maternal exposure to simulated predation risk has long-lasting effects on the cortisol response to simulated predation risk in stickleback offspring. We measured circulating concentrations of cortisol before (baseline), 15 min after, and 60 min after exposure to a simulated predation risk. We compared adult offspring of predator-exposed mothers and control mothers in two different social environments (alone or in a group). Relative to baseline, offspring plasma cortisol was highest 15 min after exposure to simulated predation risk and decreased after 60 min. Offspring of predator-exposed mothers differed in the cortisol response to simulated predation risk compared to offspring of control mothers. In general, females had higher cortisol than males, and fish in a group had lower cortisol than fish that were by themselves. The buffering effect of the social environment did not differ between maternal treatments or between males and females. Altogether the results show that while a mother's experience with simulated predation risk might affect the physiological response of her adult offspring to a predator, sex and social isolation have much larger effects on the stress response to predation risk in sticklebacks. Copyright © 2013 Elsevier Inc. All rights reserved.

Mothers' exercise during pregnancy programs vasomotor function in adult offspring

USDA-ARS?s Scientific Manuscript database

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...

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

PubMed Central

Oestreich, Arin K.; Kamp, William M.; McCray, Marcus G.; Carleton, Stephanie M.; Karasseva, Natalia; Lenz, Kristin L.; Jeong, Youngjae; Daghlas, Salah A.; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M.; Ellersieck, Mark R.; Schulz, Laura C.; Phillips, Charlotte L.

2016-01-01

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta. PMID:27821779

The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

PubMed Central

Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

2015-01-01

Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

Squamate hatchling size and the evolutionary causes of negative offspring size allometry.

PubMed

Meiri, S; Feldman, A; Kratochvíl, L

2015-02-01

Although fecundity selection is ubiquitous, in an overwhelming majority of animal lineages, small species produce smaller number of offspring per clutch. In this context, egg, hatchling and neonate sizes are absolutely larger, but smaller relative to adult body size in larger species. The evolutionary causes of this widespread phenomenon are not fully explored. The negative offspring size allometry can result from processes limiting maximal egg/offspring size forcing larger species to produce relatively smaller offspring ('upper limit'), or from a limit on minimal egg/offspring size forcing smaller species to produce relatively larger offspring ('lower limit'). Several reptile lineages have invariant clutch sizes, where females always lay either one or two eggs per clutch. These lineages offer an interesting perspective on the general evolutionary forces driving negative offspring size allometry, because an important selective factor, fecundity selection in a single clutch, is eliminated here. Under the upper limit hypotheses, large offspring should be selected against in lineages with invariant clutch sizes as well, and these lineages should therefore exhibit the same, or shallower, offspring size allometry as lineages with variable clutch size. On the other hand, the lower limit hypotheses would allow lineages with invariant clutch sizes to have steeper offspring size allometries. Using an extensive data set on the hatchling and female sizes of > 1800 species of squamates, we document that negative offspring size allometry is widespread in lizards and snakes with variable clutch sizes and that some lineages with invariant clutch sizes have unusually steep offspring size allometries. These findings suggest that the negative offspring size allometry is driven by a constraint on minimal offspring size, which scales with a negative allometry. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary

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

Opiate addiction in adult offspring through possible imprinting after obstetric treatment.

PubMed Central

Jacobson, B; Nyberg, K; Grönbladh, L; Eklund, G; Bygdeman, M; Rydberg, U

1990-01-01

OBJECTIVE--To test the hypothesis that opiate addiction in adults might stem partly from an imprinting process during birth when certain drugs are given to the mother. DESIGN--Retrospective study by logistic regression of opiate addicts with siblings as controls. SETTING--Stockholm, Sweden. SUBJECTS--200 Opiate addicts born in Stockholm during 1945-66, comprising 41 identified during interviews of probands for an earlier study; 75 patients whose death from opiate addiction had been confirmed during 1978-88; and 84 accepted for the methadone programme. 262 Siblings (controls) born in Stockholm during the same period, 24 of whom were excluded for drug addiction or being brought up outside the family. Birth records were unavailable for eight, leaving 230 siblings and 139 corresponding probands. MAIN OUTCOME MEASURES--Administration of opiates, barbiturates, and nitrous oxide (for greater than 1 h) to mothers of all subjects during labour within 10 hours before birth as a risk factor for adult opiate addiction. RESULTS--In subjects who had subsequently become addicts a significant proportion of mothers had received opiates or barbiturates, or both, compared with unmatched siblings (25% v 16%, chi 2 = 5.83, df = 1, p = 0.02), and these mothers had received nitrous oxide for longer and more often. After controlling for hospital of birth, order of birth, duration of labour, presentation other than vertex, surgical intervention, asphyxia, meconium stained amniotic fluid, and birth weight the relative risk for offspring subsequently becoming an adult opiate addict increased with the number of administrations of any of the three drugs. When the addicts were matched with their own siblings the estimated relative risk was 4.7 (95% confidence interval 1.8 to 12.4, p for trend = 0.002) for three administrations compared with when no drug was given. CONCLUSIONS--The results are compatible with the imprinting hypothesis. Therefore, for obstetric pain relief methods are preferable

Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal family study.

PubMed

MacGregor, Erica K; Grunebaum, Michael F; Galfalvy, Hanga C; Melhem, Nadine; Burke, Ainsley K; Brent, David A; Oquendo, Maria A; Mann, J John

2014-08-01

To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. 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. Parental avoidant attachment predicted offspring suicide attempts at a trend level (P = .083). Parental anxious attachment did not predict offspring attempts (P = .961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (P = .034) and, in offspring suicide attempters, was associated with greater intent (P = .045) and lethality of attempts (P = .003). Avoidant attachment in parents was associated with offspring impulsivity (P = .025) and major depressive disorder (P = .012). Parental avoidant attachment predicted a greater number of suicide attempts (P = .048) and greater intent in offspring attempters (P = .003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parental 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. © Copyright 2014 Physicians Postgraduate Press, Inc.

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

Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring.

PubMed

Canetta, Sarah E; Bao, Yuanyuan; Co, Mary Dawn T; Ennis, Francis A; Cruz, John; Terajima, Masanori; Shen, Ling; Kellendonk, Christoph; Schaefer, Catherine A; Brown, Alan S

2014-05-01

The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features. The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay. No association was observed between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serological influenza exposure was related to a significant fivefold greater risk of bipolar disorder with psychotic features. The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, these results may suggest that prenatal influenza is a risk factor for psychosis rather than for a specific psychotic disorder diagnosis.

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

PubMed Central

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; de Moura, Egberto Gaspar

2016-01-01

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

Early gut mycobiota and mother-offspring transfer.

PubMed

Schei, Kasper; Avershina, Ekaterina; Øien, Torbjørn; Rudi, Knut; Follestad, Turid; Salamati, Saideh; Ødegård, Rønnaug Astri

2017-08-24

The fungi in the gastrointestinal tract, the gut mycobiota, are now recognised as a significant part of the gut microbiota, and they may be important to human health. In contrast to the adult gut mycobiota, the establishment of the early gut mycobiota has never been described, and there is little knowledge about the fungal transfer from mother to offspring. In a prospective cohort, we followed 298 pairs of healthy mothers and offspring from 36 weeks of gestation until 2 years of age (1516 samples) and explored the gut mycobiota in maternal and offspring samples. Half of the pregnant mothers were randomised into drinking probiotic milk during and after pregnancy. The probiotic bacteria included Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus acidophilus La-5. We quantified the fungal abundance of all the samples using qPCR of the fungal internal transcribed spacer (ITS)1 segment, and we sequenced the 18S rRNA gene ITS1 region of 90 high-quantity samples using the MiSeq platform (Illumina). The gut mycobiota was detected in most of the mothers and the majority of the offspring. The offspring showed increased odds of having detectable faecal fungal DNA if the mother had detectable fungal DNA as well (OR = 1.54, p = 0.04). The fungal alpha diversity in the offspring gut increased from its lowest at 10 days after birth, which was the earliest sampling point. The fungal diversity and fungal species showed a succession towards the maternal mycobiota as the child aged, with Debaryomyces hansenii being the most abundant species during breast-feeding and Saccharomyces cerevisiae as the most abundant after weaning. Probiotic consumption increased the gut mycobiota abundance in pregnant mothers (p = 0.01). This study provides the first insight into the early fungal establishment and the succession of fungal species in the gut mycobiota. The results support the idea that the fungal host phenotype is transferred from

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

PubMed

Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

2016-11-22

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance.

PubMed

Galyon, Kristina D; Farshidi, Farnoosh; Han, Guang; Ross, Michael G; Desai, Mina; Jellyman, Juanita K

2017-03-01

The obesogenic and diabetogenic effects of the environmental toxin bisphenol A during critical windows of development are well recognized. Liver and skeletal muscle play a central role in the control of glucose production, utilization, and storage. We hypothesized that maternal bisphenol A exposure disrupts insulin signaling in rat offspring liver and skeletal muscle. We determined the protein expression of hepatic and skeletal muscle insulin signaling molecules including insulin receptor beta, its downstream target insulin receptor substrate 1 and glucose transporters (glucose transporter 2, glucose transporter 4), and hepatic glucose-regulating enzymes phosphoenolpyruvate carboxykinase and glucokinase. Rat dams had ad libitum access to filtered drinking water (control) or drinking water with bisphenol A from 2 weeks prior to mating and through pregnancy and lactation. Offspring litters were standardized to 4 males and 4 females and nursed by the same dam. At weaning, bisphenol A exposure was removed from all offspring. Glucose tolerance was tested at 6 weeks and 6 months. Liver and skeletal muscle was collected from 3 week old and 10 month old offspring for protein expression (Western blot) of insulin receptor beta, insulin receptor substrate 1, glucose transporter 2, glucose transporter 4, phosphoenolpyruvate carboxykinase, and glucokinase. Male, but not female, bisphenol A offspring had impaired glucose tolerance at 6 weeks and 6 months. Both male and female adult offspring had higher glucose-stimulated insulin secretion as well as the ratio of stimulated insulin to glucose. Male bisphenol A offspring had higher liver protein abundance of the 200 kDa insulin receptor beta precursor (2-fold), and insulin receptor substrate 1 (1.5-fold), whereas glucose transporter 2 was 0.5-fold of the control at 3 weeks of age. In adult male bisphenol A offspring, the abundance of insulin receptor beta was higher (2-fold) and glucose transporter 4 was 0.8-fold of the control in

Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

PubMed Central

Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2015-01-01

Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

NASA Astrophysics Data System (ADS)

Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2015-10-01

Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

Changes in behavioural parameters, oxidative stress and neurotrophins in the brain of adult offspring induced to an animal model of schizophrenia: The effects of FA deficient or FA supplemented diet during the neurodevelopmental phase.

PubMed

Canever, L; Freire, T G; Mastella, G A; Damázio, L; Gomes, S; Fachim, I; Michels, C; Carvalho, G; Godói, A K; Peterle, B R; Gava, F F; Valvassori, S S; Budni, J; Quevedo, J; Zugno, A I

2018-05-18

A deficiency of maternal folic acid (FA) can compromise the function and development of the brain, and may produce a susceptibility to diseases such as schizophrenia (SZ) in the later life of offspring. The aim of this study was to evaluate the effects of both FA deficient and FA supplemented diets during gestation and lactation on behavioural parameters, the markers of oxidative stress and neurotrophic factors in adult offspring which had been subjected to an animal model of SZ. Female mother rats (Dam's) were separated into experimental maternal groups, which began receiving a special diet (food) consisting of the AIN-93 diet, a control diet, or an FA deficient diet during the periods of pregnancy and lactation. Dam's receiving the control diet were further subdivided into four groups: one group received only control diet, while three groups to receive supplementation with FA at different doses (5, 10 and 50 mg/kg). Adult offspring bred from the Dam's were divided into ten groups for induction of the animal model of SZ through the administration of ketamine (Ket) (25 mg/kg). After the last administration of the drug, the animals were subjected to the behavioural tests and were then euthanized. The frontal cortex (FC) and hippocampus (Hip) were then dissected for later biochemical analysis. Our data demonstrates that Ket induced the model of SZ by altering the behavioural parameters (e.g. hyperlocomotion, social impairment, deficits in the sensory-motor profile and memory damage in the adult animals); and also caused changes in the parameters of oxidative stress (lipid hydroperoxide - LPO; 8-isoprostane - 8-ISO; 4-hydroxynonenal - 4-HNE; protein carbonyl content; superoxide dismutase - SOD and catalase - CAT) as well as in the levels of neurotrophic factors (brain-derived neurotrophic factor - BDNF and nerve growth factor - NGF) particularly within the FC of adult offspring. A deficiency in maternal FA, alone or in combination with ket, was able to induce

Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring.

PubMed

Solati, Jalal; Hajikhani, Ramin; Rashidieh, Behnam; Jalilian, Mahshid Fatipour

2012-04-01

Maternal infection during pregnancy is a risk factor for some behavioral problems with neurodevelopmental origin. This study aimed to evaluate the effects of exposure of pregnant mice to the bacterial lipopolysaccharide (LPS) on sexual behaviour and serum level of pituitary-gonadal hormones of offspring in adulthood. In this Expremental study, pregnant NMRI mice (n=7/group) were treated with intra-peritoneal administration of LPS (1, 5 and 10 µg/kg) at day 10 of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were measured in maternal serum 2 hours following the maternal LPS challenge. Behavior in the adult male offspring reproductive activity was investigated using receptive female mice. Concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult offspring serum were measured using the enzyme-linked immunosorbent assay (ELISA) method (at postnatal day 60, n=10/group). One-way ANOVA showed that LPS administration induces a significant increase in TNF-α, IL-1β and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexual behavior and serum concentration of LH and testosterone in adult male offspring. The overall results suggest that prenatal exposure to LPS increases pro- inflammatory cytokine levels, affects development of neuroendocrine systems and results in the inhibition of reproductive behaviors and reactivity of hypothalamic-pituitary-gonadal (HPG) axis in adult male offspring.

Effect of oral zinc supplementation upon Taenia crassiceps murine cysticercosis.

PubMed

Fragoso, G; Lastra, M D; Aguilar, A E; Pastelin, R; Rosas, G; Meneses, G; Sciutto, E; Lamoyi, E

2001-10-01

The effect of zinc supplementation on Taenia crassiceps murine cysticercosis was studied in susceptible BALB/cAnN mice. Female offspring of mice supplemented with high zinc throughout gestation and lactation were intraperitoneally infected with T. crassiceps cysticerci. Offspring from nonsupplemented mothers were used as controls. Significantly fewer parasites were recovered from zinc-supplemented mice (Zsm) 30 days after infection. Increased resistance was not related to the IgG antibody response. At early stages of infection, T cells from Zsm proliferated to T. crassiceps antigens, whereas cells from control mice did not respond. Infection caused in both groups a decrease in CD3+ cell percentages, which was more pronounced in the controls, and paralleled by a decrease in CD8+ cells; CD3+ and CD8+ percentages returned to normal levels at later stages of infection. In contrast, the CD4+ subpopulation only decreased in control mice. Intracellular cytokine determinations indicate that zinc supplementation favored a stronger and persistent type-1 T cell response in cysticerci-infected mice, which probably participates in the observed increased resistance.

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

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

Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo

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 causesmore » 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

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

2015-08-07

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Influence of maternal obesity on the long-term health of offspring

PubMed Central

Godfrey, Keith M.; Reynolds, Rebecca M.; Prescott, Susan L.; Nyirenda, Moffat; Jaddoe, Vincent W.V.; Eriksson, Johan G.; Broekman, Birit F.P

2017-01-01

Alongside its immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of health in the offspring during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on the offspring’s risks of obesity, coronary heart disease, stroke, type 2 diabetes and asthma. Maternal obesity may also lead to poorer cognitive performance in the offspring and an increased risk of neurodevelopmental disorders including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious disease related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, mediated at least in part through changes in epigenetic processes including alternations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight prior to pregnancy have a reduced risk of obesity, to date few controlled intervention studies have reversed maternal obesity and examined the consequences for the offspring. The long term effects of maternal obesity may have profound public health implications and indicate the urgency of studies on causality, underlying mechanisms and effective interventions to reverse the epidemic of obesity in women of child-bearing age and to mitigate its consequences for the offspring. PMID:27743978

Serological Documentation of Maternal Influenza Exposure and Bipolar Disorder in Adult Offspring

PubMed Central

Canetta, Sarah E.; Bao, Yuanyuan; Co, Mary Dawn T.; Ennis, Francis A.; Cruz, John; Terajima, Masanori; Shen, Ling; Kellendonk, Christoph; Schaefer, Catherine A.; Brown, Alan S.

2014-01-01

Objective The goal of the present study was to evaluate whether serologically confirmed maternal exposure to influenza is associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features. Method The study utilized a nested case-control design in the Child Health and Development Study birth cohort. Eighty-five cases of bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 controls in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay. Results There was no association between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serologic influenza exposure was related to a significant, fivefold increased risk of bipolar disorder with psychotic features. Conclusions These results suggest that maternal influenza exposure may increase the risk for the offspring developing bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, this may suggest that prenatal influenza is a risk factor for psychosis, rather than for a specific psychotic disorder diagnosis. PMID:24480930

Sense and sensitivity: responsiveness to offspring signals varies with the parents' potential to breed again

PubMed Central

Thorogood, Rose; Ewen, John G.; Kilner, Rebecca M.

2011-01-01

How sensitive should parents be to the demands of their young? Offspring are under selection to seek more investment than is optimal for parents to supply, which makes parents vulnerable to losing future fitness by responding to manipulative displays. Yet, parents cannot afford to ignore begging and risk allocating resources inefficiently. Here, we show that parents may solve this problem by adjusting their sensitivity to begging behaviour in relation to their own likelihood of breeding again, a factor largely neglected in previous analyses of parent–offspring interactions. In two carotenoid-supplementation experiments on a New Zealand passerine, the hihi Notiomystis cincta, we supplemented adults to enhance their propensity to breed again, and supplemented entire broods to increase their mouth colour, thus enhancing their solicitation display. We found that adults that attempted two breeding attempts a season were largely insensitive to the experimentally carotenoid-rich gapes of their brood, whereas those that bred just once responded by increasing their rate of provisioning at the nest. Our results show that parents can strategically vary their sensitivity to begging in relation to their future reproductive potential. By restricting opportunities for offspring to influence provisioning decisions, parents greatly limit the potential for offspring to win parent–offspring conflict. PMID:21270035

Maternal modulation of paternal effects on offspring development

PubMed Central

Habrylo, Ireneusz B.; Gudsnuk, Kathryn M.; Pelle, Geralyn; Champagne, Frances A.

2018-01-01

The paternal transmission of environmentally induced phenotypes across generations has been reported to occur following a number of qualitatively different exposures and appear to be driven, at least in part, by epigenetic factors that are inherited via the sperm. However, previous studies of paternal germline transmission have not addressed the role of mothers in the propagation of paternal effects to offspring. We hypothesized that paternal exposure to nutritional restriction would impact male mate quality and subsequent maternal reproductive investment with consequences for the transmission of paternal germline effects. In the current report, using embryo transfer in mice, we demonstrate that sperm factors in adult food restricted males can influence growth rate, hypothalamic gene expression and behaviour in female offspring. However, under natural mating conditions females mated with food restricted males show increased pre- and postnatal care, and phenotypic outcomes observed during embryo transfer conditions are absent or reversed. We demonstrate that these compensatory changes in maternal investment are associated with a reduced mate preference for food restricted males and elevated gene expression within the maternal hypothalamus. Therefore, paternal experience can influence offspring development via germline inheritance, but mothers can serve as a modulating factor in determining the impact of paternal influences on offspring development. PMID:29514964

Maternal modulation of paternal effects on offspring development.

PubMed

Mashoodh, Rahia; Habrylo, Ireneusz B; Gudsnuk, Kathryn M; Pelle, Geralyn; Champagne, Frances A

2018-03-14

The paternal transmission of environmentally induced phenotypes across generations has been reported to occur following a number of qualitatively different exposures and appear to be driven, at least in part, by epigenetic factors that are inherited via the sperm. However, previous studies of paternal germline transmission have not addressed the role of mothers in the propagation of paternal effects to offspring. We hypothesized that paternal exposure to nutritional restriction would impact male mate quality and subsequent maternal reproductive investment with consequences for the transmission of paternal germline effects. In the current report, using embryo transfer in mice, we demonstrate that sperm factors in adult food restricted males can influence growth rate, hypothalamic gene expression and behaviour in female offspring. However, under natural mating conditions females mated with food restricted males show increased pre- and postnatal care, and phenotypic outcomes observed during embryo transfer conditions are absent or reversed. We demonstrate that these compensatory changes in maternal investment are associated with a reduced mate preference for food restricted males and elevated gene expression within the maternal hypothalamus. Therefore, paternal experience can influence offspring development via germline inheritance, but mothers can serve as a modulating factor in determining the impact of paternal influences on offspring development. © 2018 The Author(s).

Remarkable Shifts in Offspring Provisioning during Gestation in a Live-Bearing Cnidarian

PubMed Central

Mercier, Annie; Sun, Zhao; Parrish, Christopher C.; Hamel, Jean-François

2016-01-01

Animals display diverse means of producing and provisioning offspring, from eggs to embryos and juveniles. While external development predominates, many forms of embryonic incubation have evolved, including placentation in mammals and a number of understudied variants in basal metazoans that could help understand evolutionary diversification. Here we studied the brooding sea anemone Aulactinia stella, using behavioural, morphological and biochemical indicators of offspring phenotype to characterize gestation and elucidate parental and sibling relationships. The pronounced variance in juvenile weight within broods was not strongly related to any of the typical external predictors (adult weight, clutch size, sampling date, environmental conditions). Lipid concentration was significantly higher in the tissues of the small juveniles than in those of large juveniles or adult, and fatty acid profiles tended to set small juveniles apart. Finally, intra-brood feeding on external resources was documented in larger juveniles. These results are consistent with ontogenetic shifts in nutrition, from vitellogenic provisioning to post-zygotic nourishment to a prenatal form of nursing upon acquisition of feeding organs, highlighting matrotrophic and conflict-driven mechanisms acting on offspring phenotype during gestation. PMID:27104375

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

PubMed Central

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

2016-01-01

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 (pre-mating), 2) at separation (post-mating), 3) at mid-pregnancy, 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 post-mating 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

Development of a nematode offspring counting assay for rapid and simple soil toxicity assessment.

PubMed

Kim, Shin Woong; Moon, Jongmin; Jeong, Seung-Woo; An, Youn-Joo

2018-05-01

Since the introduction of standardized nematode toxicity assays by the American Society for Testing and Materials (ASTM) and International Organization for Standardization (ISO), many studies have reported their use. Given that the currently used standardized nematode toxicity assays have certain limitations, in this study, we examined the use of a novel nematode offspring counting assay for evaluating soil ecotoxicity based on a previous soil-agar isolation method used to recover live adult nematodes. In this new assay, adult Caenorhabditis elegans were exposed to soil using a standardized toxicity assay procedure, and the resulting offspring in test soils attracted by a microbial food source in agar plates were counted. This method differs from previously used assays in terms of its endpoint, namely, the number of nematode offspring. The applicability of the bioassay was demonstrated using metal-spiked soils, which revealed metal concentration-dependent responses, and with 36 field soil samples characterized by different physicochemical properties and containing various metals. Principal component analysis revealed that texture fraction (clay, sand, and silt) and electrical conductivity values were the main factors influencing the nematode offspring counting assay, and these findings warrant further investigation. The nematode offspring counting assay is a rapid and simple process that can provide multi-directional toxicity assessment when used in conjunction with other standard methods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Murine model for congenital CMV infection and hearing impairment

PubMed Central

2011-01-01

Background Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL. PMID:21320351

Murine model for congenital CMV infection and hearing impairment.

PubMed

Juanjuan, Chen; Yan, Feng; Li, Chen; Haizhi, Liu; Ling, Wang; Xinrong, Wang; Juan, Xiao; Tao, Liu; Zongzhi, Yin; Suhua, Chen

2011-02-15

Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging in Offspring of Holocaust Survivors

PubMed Central

Shrira, Amit; Ayalon, Liat; Bensimon, Moshe; Bodner, Ehud; Rosenbloom, Tova; Yadid, Gal

2017-01-01

A fascinating, yet underexplored, question is whether traumatic events experienced by previous generations affect the aging process of subsequent generations. This question is especially relevant for offspring of Holocaust survivors (OHS), who begin to face the aging process. Some preliminary findings point to greater physical dysfunction among middle-aged OHS, yet the mechanisms behind this dysfunction need further clarification. Therefore, the current studies assess aging OHS using the broad-scoped conceptualization of successful aging, while examining whether offspring successful aging relates to parental post-traumatic stress disorder (PTSD) symptoms and offspring’s secondary traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31) completed measures of parental PTSD, secondary traumatization, as well as successful aging indices – objective (medical conditions, disability and somatic symptoms) and subjective (perceptions of one’s aging). Relative to comparisons and OHS who reported that none of their parents suffered from probable PTSD, OHS who reported that their parents suffered from probable PTSD had lower scores in objective and subjective measures of successful aging. Mediation analyses showed that higher level of secondary traumatization mediated the relationship between parental PTSD and less successful aging in the offspring. Study 2 included 154 dyads of parents (mean age = 81.86) and their adult offspring (mean age = 54.48). Parents reported PTSD symptoms and offspring reported secondary traumatization and completed measures of objective successful aging. Relative to comparisons, OHS whose parent had probable PTSD have aged less successfully. Once again, offspring secondary traumatization mediated the effect. The findings suggest that parental post-traumatic reactions assessed both by offspring (Study 1) and by parents themselves (Study 2) take part in shaping the aging of the subsequent generation via reactions of secondary

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

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

Martinez–Arguelles, D.B.; Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4; McIntosh, M.

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressuremore » in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.« less

Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

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

Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de

Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activitymore » and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.« less

Maternal fructose-intake-induced renal programming in adult male offspring.

PubMed

Tain, You-Lin; Wu, Kay L H; Lee, Wei-Chia; Leu, Steve; Chan, Julie Y H

2015-06-01

Nutrition in pregnancy can elicit long-term effects on the health of offspring. Although fructose consumption has increased globally and is linked to metabolic syndrome, little is known about the long-term effects of maternal high-fructose (HF) exposure during gestation and lactation, especially on renal programming. We examined potential key genes and pathways that are associated with HF-induced renal programming using whole-genome RNA next-generation sequencing (NGS) to quantify the abundance of RNA transcripts in kidneys from 1-day-, 3-week-, and 3-month-old male offspring. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) during the entire period of pregnancy and lactation. Male offspring exhibited programmed hypertension at 3 months of age. Maternal HF intake modified over 200 renal transcripts from nephrogenesis stage to adulthood. We observed that 20 differentially expressed genes identified in 1-day-old kidney are related to regulation of blood pressure. Among them, Hmox1, Bdkrb2, Adra2b, Ptgs2, Col1a2 and Tbxa2r are associated with endothelium-derived hyperpolarizing factor (EDHF). NGS also identified genes in arachidonic acid metabolism (Cyp2c23, Hpgds, Ptgds and Ptges) that may be potential key genes/pathways contributing to renal programming and hypertension. Collectively, our NGS data suggest that maternal HF intake elicits a defective adaptation of interrelated EDHFs during nephrogenesis which may lead to renal programming and hypertension in later life. Moreover, our results highlight genes and pathways involved in renal programming as potential targets for therapeutic approaches to prevent metabolic-syndrome-related comorbidities in children with HF exposure in early life. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

PubMed

Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

2016-11-01

Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

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…

Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis.

PubMed

Haensgen, Henny; Albornoz, Eduardo; Opazo, María C; Bugueño, Katherinne; Jara Fernández, Evelyn Liliana; Binzberger, Rebecca; Rivero-Castillo, Tomás; Venegas Salas, Luis F; Simon, Felipe; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Kalergis, Alexis M; Bueno, Susan M; Riedel, Claudia A

2018-01-01

Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4 + CD25 + T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (T Eff ) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4 + CD25 + T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of T reg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4 + CD25 + from spleen have reduced capacity to differentiate in vitro to T reg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such "imprints" on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE.

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.

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.

Schizotypal and affective traits in the offspring of antenatally depressed mothers - Relationship to family history of psychosis in the Northern Finland 1966 Birth Cohort.

PubMed

Taka-Eilola Née Riekki, T; Miettunen, J; Mäki, P

2017-05-01

Maternal depression is relatively common during pregnancy. However, follow-ups of the adult offspring of antenatally depressed mothers are scarce. Previously we found the risk of schizophrenia to be higher in the adult offspring with antenatally depressed mothers and parents with psychosis than in subjects with only one or neither of these risk factors. The aim was to study whether the risk of schizotypal or affective traits differ among adult offspring with antenatally depressed mothers with or without a parental history of psychosis when compared with offspring without antenatally depressed mothers and without parental psychosis. In the general population-based Northern Finland 1966 Birth Cohort (NFBC 1966), the mothers of the cohort members were asked at mid-gestation whether they felt depressed. Parental psychosis (Familial Risk, FR) was detected using the Finnish Care Register for Health Care. In the 31-year field study, seven psychometric questionnaires surveyed schizotypal and affective traits in the offspring. The final sample included 4928 individuals (2203 males). There were no statistically significant differences in mean scores on the schizotypal and affective scales between offspring with and without antenatally depressed mothers, or between subjects with and without parental psychosis. The scores were not highest in the subjects with both maternal antenatal depressed mood and FR. Surprisingly, maternal depressed mood during pregnancy was unlikely to increase the risk of schizotypy or affective traits in adult offspring, and not even with parental psychosis (FR) in this general population-based birth cohort with about 5000 subjects. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Maternal, not paternal PTSD, is related to increased risk for PTSD in offspring of Holocaust survivors

PubMed Central

Yehuda, Rachel; Bell, Amanda; Bierer, Linda M.; Schmeidler, James

2008-01-01

Background A significant association between parental PTSD and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low cortisol in offspring prompted us to examine the relative contributions of maternal vs. paternal PTSD in the prediction of PTSD and other psychiatric diagnoses. Methods 117 men and 167 women, recruited from the community, were evaluated using a comprehensive psychiatric battery designed to identify traumatic life experiences and lifetime psychiatric diagnoses. 211 of the subjects were the adult offspring of Holocaust survivors and 73 were demographically comparable Jewish controls. Participants were further subdivided based on whether their mother, father, neither, or both parents met the diagnostic criteria for lifetime PTSD. Results A higher prevalence of lifetime PTSD, mood, anxiety disorders, and to a lesser extent, substance abuse disorders, was observed in offspring of Holocaust than controls. The presence of maternal PTSD was specifically associated with PTSD in adult offspring. However, the other diagnoses did not show specific effects associated with maternal PTSD. Conclusion The tendency for maternal PTSD to make a greater contribution to PTSD risk suggests that classic genetic mechanisms are not the sole model of transmission, and pave way for the speculation that epigenetic factors may be involved. In contrast, PTSD in any parent contributes to risk for depression, and parental traumatization is associated with increased anxiety disorders in offspring. PMID:18281061

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'…

When parents disclose BRCA1/2 test results: their communication and perceptions of offspring response.

PubMed

Bradbury, Angela R; Patrick-Miller, Linda; Egleston, Brian L; Olopade, Olufunmilayo I; Daly, Mary B; Moore, Cynthia W; Sands, Colleen B; Schmidheiser, Helen; Kondamudi, Preethi K; Feigon, Maia; Ibe, Comfort N; Daugherty, Christopher K

2012-07-01

BRCA1/2 testing is not recommended for children, as risk reduction measures and screening are not generally recommended before 25 years old (YO). Little is known about the prevalence and predictors of parent communication to offspring and how offspring respond to this communication. Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least 1 child <25 YO. Logistic regressions were utilized to evaluate associations with communication. Framework analysis was utilized to analyze open-ended responses. A total of 253 parents completed interviews (61% response rate), reporting on 505 offspring. Twenty-nine percent of parents were BRCA1/2 mutation carriers. Three hundred thirty-four (66%) offspring learned of their parent's test result. Older offspring age (P ≤ .01), offspring gender (female, P = .05), parents' negative test result (P = .03), and parents' education (high school only, P = .02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). Thirteen percent of offspring were reported to experience concern or distress (11%) in response to parental communication of their test results. Distress was more frequently perceived among offspring learning of their parent's BRCA1/2 positive or variant of uncertain significance result. Many parents communicate their BRCA1/2 test results to young offspring. Parents' perceptions of offspring responses appear to vary by offspring age and parent test result. A better understanding of how young offspring respond to information about hereditary risk for adult cancer could provide opportunities to optimize adaptive psychosocial responses to risk information and performance of health behaviors, in adolescence and throughout an at-risk life span. Copyright © 2012 American Cancer Society.

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. © 2016 by the Society for the Study of Reproduction, Inc.

Maternal exposure to the holocaust and health complaints in offspring.

PubMed

Flory, Janine D; Bierer, Linda M; Yehuda, Rachel

2011-01-01

Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and self-reported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring's own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved.

Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators.

PubMed

Desai, Mina; Han, Guang; Ross, Michael G

2016-04-01

Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Programmed Hyperphagia in Offspring of Obese Dams: Altered Expression of Hypothalamic Nutrient Sensors, Neurogenic Factors and Epigenetic Modulators

PubMed Central

Desai, Mina; Han, Guang; Ross, Michael G.

2016-01-01

Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. PMID:26785315

Prenatal hypoxia promotes atherosclerosis via vascular inflammation in the offspring rats.

PubMed

Zhang, Pengjie; Zhu, Di; Chen, Xionghui; Li, Yongmei; Li, Na; Gao, Qinqin; Li, Lingjun; Zhou, Xiuwen; Lv, Juanxiu; Sun, Miao; Mao, Caiping; Xu, Zhice

2016-02-01

Hypoxia is a critical contributor to increased risks of cardiovascular diseases, including atherosclerosis, but the detailed mechanism that hypoxia leads to atherosclerosis remains unknown. Pregnant rats were treated with hypoxia (10.5% oxygen) during pregnancy, and HUVEC cells treated with 1% of oxygen. Blood lipids were tested at fetal stage and adult stage of offspring rats; the level of pro-inflammatory cytokines of HUVEC and offspring rats were investigated, and HIF-1α and NFκB mRNA level were also measured by Q-PCR and Elisa. We found that TC, LDL-C, ox-LDL-C, and the receptors of ox-LDL-C (lox-1) of the adult offspring were significantly higher than that of the control, while HDL-C was significantly reduced in hypoxia group. The internal elastic lamina was blocked by smooth muscle cells; and the migration of smooth muscle cells into the intima were observed in hypoxia offspring. Luciferase reporter gene experiment showed that HIF-1α activated NFκB transcription at four discrete binding sites of NFκBp65 promoter, although there was no obvious difference among the four discrete binding sites. Using transfection of pCDNA3.1-HIF-1α on HUVEC cells, HIF-1α significantly activated NFκB transcription at hypoxic conditions (1% O2), and concurrent with increased expression of IL-1β and TNF-α. Hypoxia during pregnancy activated NFκB transcription to induce pro-inflammatory cytokines, leading to the early stage of atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Early Life Fructose Exposure and Its Implications for Long-Term Cardiometabolic Health in Offspring.

PubMed

Zheng, Jia; Feng, Qianyun; Zhang, Qian; Wang, Tong; Xiao, Xinhua

2016-11-01

It has become increasingly clear that maternal nutrition can strongly influence the susceptibility of adult offspring to cardiometabolic disease. For decades, it has been thought that excessive intake of fructose, such as sugar-sweetened beverages and foods, has been linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. These deleterious effects of excess fructose consumption in adults are well researched, but limited data are available on the long-term effects of high fructose exposure during gestation, lactation, and infancy. This review aims to examine the evidence linking early life fructose exposure during critical periods of development and its implications for long-term cardiometabolic health in offspring.

Role of maternal 5-HT(1A) receptor in programming offspring emotional and physical development.

PubMed

van Velzen, A; Toth, M

2010-11-01

Serotonin(1A) receptor (5-HT(1A)R) deficiency has been associated with anxiety and depression and mice with genetic receptor inactivation exhibit heightened anxiety. We have reported that 5-HT(1A)R is not only a genetic but also a maternal 'environmental' factor in the development of anxiety in Swiss-Webster mice. Here, we tested whether the emergence of maternal genotype-dependent adult anxiety is preceded by early behavioral abnormalities or whether it is manifested following a normal emotional development. Pups born to null or heterozygote mothers had significantly reduced ultrasonic vocalization (USV) between postnatal day (P) 4 and 12, indicating an influence of the maternal genotype. The offspring's own genotype had an effect limited to P4. Furthermore, we observed reduced weight gain in the null offspring of null but not heterozygote mothers, indicating that a complete maternal receptor deficiency compromises physical development of the offspring. Except a short perinatal deficit during the dark period, heterozygote females displayed normal maternal behavior, which, with the early appearance of USV deficit, suggests a role for 5-HT(1A)R during pre-/perinatal development. Consistent with this notion, adult anxiety in the offspring is determined during the pre-/perinatal period. In contrast to heterozygote females, null mothers exhibited impaired pup retrieval and nest building that may explain the reduced weight gain of their offspring. Taken together, our data indicate an important role for the maternal 5-HT(1A)R in regulating emotional and physical development of their offspring. Because reduced receptor binding has been reported in depression, including postpartum depression, reduced 5-HT(1A)R function in mothers may influence the emotional development of their offspring. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Suicidal risk in young adult offspring of mothers with bipolar or major depressive disorder: a longitudinal family risk study.

PubMed

Klimes-Dougan, Bonnie; Lee, Chih-Yuan S; Ronsaville, Donna; Martinez, Pedro

2008-04-01

Recent evidence has highlighted suicidal risk associated with bipolar disorder (BD). Using a family risk approach, the goal of this study was to evaluate suicidal thoughts and behaviors longitudinally from childhood to young adulthood in children of mothers with BD, Major depressive disorder (MDD), and well mothers. Few group differences were found for cross-sectional assessments of suicidal thoughts and behavior in young adulthood; the offspring of MDD demonstrate an earlier onset and more persistent suicidality than other groups, but by young adulthood, BD offspring appear to be comparable to MDD offspring in their rates of suicidality. The longitudinal assessments reveal a pattern of higher suicidal risk in MDD offspring, more intermediate risk in BD offspring, and lower risk in well offspring. Precursors and correlates of suicidal thoughts and behaviors were also examined. These findings suggest diverse developmental trajectories based on family risk and have implications for planning preventive intervention.

Age, pathogen exposure, but not maternal care shape offspring immunity in an insect with facultative family life.

PubMed

Vogelweith, Fanny; Körner, Maximilian; Foitzik, Susanne; Meunier, Joël

2017-03-07

To optimize their resistance against pathogen infection, individuals are expected to find the right balance between investing into the immune system and other life history traits. In vertebrates, several factors were shown to critically affect the direction of this balance, such as the developmental stage of an individual, its current risk of infection and/or its access to external help such as parental care. However, the independent and/or interactive effects of these factors on immunity remain poorly studied in insects. Here, we manipulated maternal presence and pathogen exposure in families of the European earwig Forficula auricularia to measure whether and how the survival rate and investment into two key immune parameters changed during offspring development. The pathogen was the entomopathogenic fungus Metarhizium brunneum and the immune parameters were hemocyte concentration and phenol/pro-phenoloxidase enzyme activity (total-PO). Our results surprisingly showed that maternal presence had no effect on offspring immunity, but reduced offspring survival. Pathogen exposure also lowered the survival of offspring during their early development. The concentration of hemocytes and the total-PO activity increased during development, to be eventually higher in adult females compared to adult males. Finally, pathogen exposure overall increased the concentration of hemocytes-but not the total-PO activity-in adults, while it had no effect on these measures in offspring. Our results show that, independent of their infection risk and developmental stage, maternal presence does not shape immune defense in young earwigs. This reveals that pathogen pressure is not a universal evolutionary driver of the emergence and maintenance of post-hatching maternal care in insects.

Inbreeding depression in an insect with maternal care: influences of family interactions, life stage and offspring sex.

PubMed

Meunier, J; Kölliker, M

2013-10-01

Although inbreeding is commonly known to depress individual fitness, the severity of inbreeding depression varies considerably across species. Among the factors contributing to this variation, family interactions, life stage and sex of offspring have been proposed, but their joint influence on inbreeding depression remains poorly understood. Here, we demonstrate that these three factors jointly shape inbreeding depression in the European earwig, Forficula auricularia. Using a series of cross-breeding, split-clutch and brood size manipulation experiments conducted over two generations, we first showed that sib mating (leading to inbred offspring) did not influence the reproductive success of earwig parents. Second, the presence of tending mothers and the strength of sibling competition (i.e. brood size) did not influence the expression of inbreeding depression in the inbred offspring. By contrast, our results revealed that inbreeding dramatically depressed the reproductive success of inbred adult male offspring, but only had little effect on the reproductive success of inbred adult female offspring. Overall, this study demonstrates limited effects of family interactions on inbreeding depression in this species and emphasizes the importance of disentangling effects of sib mating early and late during development to better understand the evolution of mating systems and population dynamics. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

The Role of Depression in the Differential Effect of Childhood Parental Divorce on Male and Female Adult Offspring Suicide Attempt Risk

PubMed Central

Lizardi, Dana; Thompson, Ronald G.; Keyes, Katherine; Hasin, Deborah

2013-01-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized. PMID:20823733

The role of depression in the differential effect of childhood parental divorce on male and female adult offspring suicide attempt risk.

PubMed

Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

2010-09-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized.

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

Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

NASA Technical Reports Server (NTRS)

Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

2017-01-01

DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

Like mother, like child: Offspring marital timing desires and maternal marriage timing and stability.

PubMed

Arocho, Rachel; Kamp Dush, Claire M

2017-04-01

Understanding the determinants of marital timing is critical because it has implications for marital functioning and divorce. One salient predictor of marital timing is youth's desires for marriage timing. To shine light on predictors of both desires for marital timing and the timing of marriage itself, we examine offspring marital desires and maternal marriage characteristics in the National Longitudinal Survey of Youth, 1979 (NLSY79) cohort and 1979 Child and Young Adult cohort (NLSY79-CYA; biological offspring of the women in the 1979 cohort). Analyses showed that maternal cohabitation postdivorce predicted decreased expectations to ever marry in offspring. Maternal age at marriage was positively associated with offspring desires for age at marriage, but only for those whose mothers had not divorced. Maternal marital age was significantly associated with the offspring's transition into marriage even when controlling for the offspring's desires for marriage timing, but neither maternal marriage age nor offspring desires for marital timing were associated with the timing of entrance into cohabitation, whereas maternal divorce was associated with earlier cohabitation. Our findings suggest that maternal marriage characteristics, particularly divorce, are significant predictors of millennials' desires for and experiences with romantic relationships. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed Central

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

2013-01-01

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

Pathways to suicide-related behavior in offspring of mothers with depression: the role of offspring psychopathology.

PubMed

Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

2015-05-01

Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers' first 11 years of their child's life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology

PubMed Central

Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M.; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

2015-01-01

Objective Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Method Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Conclusion Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. PMID:25901775

Maternal handling during pregnancy reduces DMBA-induced mammary tumorigenesis among female offspring.

PubMed Central

Hilakivi-Clarke, L.

1997-01-01

The present study investigated whether handling of pregnant rats would affect mammary tumorigenesis in their female offspring. Pregnant Sprague-Dawley rats were injected daily with 0.05 ml of vehicle between days 14 and 20 of gestation or were left undisturbed. Handling did not have any effects on pregnancy or early development of the offspring. The female offspring were administered 10 mg of 7,12-dimethylbenz(a)anthracene (DMBA) at the age of 55 days. The rats whose mothers were handled during pregnancy had a significantly reduced mammary tumour incidence when compared with the offspring of non-handled mothers. Thus, on week 18 after DMBA exposure, 15% of the handled offspring had developed mammary tumours, whereas 44% of the non-handled offspring had tumours. No significant differences in the latency to tumour appearance, in the size of the tumours or in their growth rates were noted. Daily handling performed during post-natal days 5 and 20 produced similar data to that obtained for prenatal handling; on week 18 after DMBA exposure, the mammary tumour incidence among the post-natally handled rats was 22% and among the non-handled rats 44%. Possible deviations in hormonal parameters were also studied in adult female rats exposed in utero to handling. The onset of puberty tended to occur later among the handled offspring, but no differences in the uterine wet weights or serum oestradiol levels between the groups were noted. In conclusion, maternal handling reduced the offspring's risk to develop mammary tumours, and this effect was independent of the oestrogenic environment at adulthood. We propose that handling of a pregnant rat reduces mammary tumorigenesis in her offspring by means of changing the morphology of the mammary gland, the pattern of expression of specific genes and/or immune functions. PMID:9231913

Like mother, like offspring: maternal and offspring wound healing correlate in snakes.

PubMed

Hopkins, Brittney C; Chin, Stephanie Y; Willson, John D; Hopkins, William A

2013-07-15

Immune function early in life can be influenced by parental effects and the environment, but it remains unclear how these two factors may interact to influence immunocompetence. We evaluated maternal and environmental contributions to offspring healing ability in a viviparous reptile, the northern watersnake (Nerodia sipedon). We measured wound healing rates, a highly integrative and biologically relevant measure of innate immunity, of females and their offspring collected from sites contaminated with a toxic heavy metal and compared them with those of individuals from reference sites. We found that female watersnakes that healed the fastest produced offspring that also exhibited faster healing rates. However, we detected no influence of environmental pollution on maternal or offspring healing rates. To our knowledge, our study is the first to correlate maternal and offspring wound healing ability in a wild vertebrate.

Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study.

PubMed

Sanchez-Gistau, Vanessa; Romero, Soledad; Moreno, Dolores; de la Serna, Elena; Baeza, Inmaculada; Sugranyes, Gisela; Moreno, Carmen; Sanchez-Gutierrez, Teresa; Rodriguez-Toscano, Elisa; Castro-Fornieles, Josefina

2015-10-01

Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. SZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP. Copyright © 2015 Elsevier B.V. All rights reserved.

Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

PubMed

Manti, Maria; Fornes, Romina; Qi, Xiaojuan; Folmerz, Elin; Lindén Hirschberg, Angelica; de Castro Barbosa, Thais; Maliqueo, Manuel; Benrick, Anna; Stener-Victorin, Elisabet

2018-03-22

Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.

PubMed

Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi

2015-01-01

Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring.

PubMed

Ferreira, Diorginis Soares; Liu, Yuri; Fernandes, Mariana Pinheiro; Lagranha, Claudia Jacques

2016-10-01

Studies in humans and animal models have established a close relationship between early environment insult and subsequent risk of development of non-communicable diseases, including the cardiovascular. Whereas experimental evidences highlight the early undernutrition and the late cardiovascular disease relation, the central mechanisms linking the two remain unknown. Owing to the oxidative balance influence in several pathologies, the aim of the present study was to evaluate the effects of maternal undernutrition (i.e. a low-protein (LP) diet) on oxidative balance in the brainstem. Male rats from mothers fed with an LP diet (8% casein) throughout the perinatal period (i.e. gestation and lactation) showed 10× higher lipid peroxidation levels than animals treated with normoprotein (17% casein) at 100 days of age. In addition, we observed the following reductions in enzymatic activities: superoxide dismutase, 16%; catalase, 30%; glutathione peroxidase, 34%; glutathione-S-transferase, 51%; glutathione reductase, 23%; glucose-6-phosphate dehydrogenase, 31%; and in non-enzymatic glutathione system, 46%. This study is the first to focus on the role of maternal LP nutrition in oxidative balance in a central nervous system structure responsible for cardiovascular control in adult rats. Our data observed changes in oxidative balance in the offspring, therefore, bring a new concept related to early undernutrition and can help in the development of a new clinical strategy to combat the effects of nutritional insult. Wherein the central oxidative imbalance is a feasible mechanism underlying the hypertension risk in adulthood triggered by maternal LP diet.

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.

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

Maternal protein-free diet during lactation programs male Wistar rat offspring for increased novelty-seeking, locomotor activity, and visuospatial performance.

PubMed

Lotufo, Bruna M; Tenório, Frank; Barradas, Penha C; Guedes, Paulo L; Lima, Sebastião S; Rocha, Michael L M; Duarte-Pinheiro, Vitor Hugo; Rodrigues, Vanessa S T; Lisboa, Patrícia C; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Manhães, Alex C

2018-04-01

It is well established that chronic undernutrition has detrimental impacts on brain development and maturation. However, protein malnutrition during the period specifically encompassing the brain growth spurt has not been widely studied, particularly regarding its effects on adolescent and adult offspring behavior. Here, we assessed the effects of a protein-free diet during the 1st 10 postnatal days on the macronutrient content of the milk produced by lactating Wistar rats, on their maternal behavior, and on the offspring's behavior. Lactating dams were fed either a protein-free or a normoprotein diet from litter parturition to Postnatal Day 10 (P10). All dams received the normoprotein diet after P10. Offspring were tested in the elevated plus-maze (anxiety-like behavior), hole board arena (novelty-seeking and locomotor activity), and radial arm water maze (memory-learning) at either P40 (adolescents) or P90 (adults). The protein-free diet reduced milk protein content at P10 but not at P20. Carbohydrate and lipid contents were unaffected. Serum corticosterone levels in the offspring (at P10, P40, or P90) and dams (at P21) were not affected by the protein-free diet. Maternal behavior was also unchanged. In the offspring, no differences were observed between groups regarding anxiety-like behaviors at both ages. The protein-free diet increased adolescent locomotor activity as well as adult novelty-seeking behavior and memory performance. Our results indicate that the brain growth spurt period is particularly sensitive to protein malnutrition, showing that even a brief nutritional insult during this period can cause specific age-dependent behavioral effects on the offspring. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes

USDA-ARS?s Scientific Manuscript database

Developmental epigenetic changes, such as DNA methylation, have been recognized as potential pathogenic factors in inflammatory bowel diseases, the hallmark of which is an exaggerated immune response against luminal microbes. A methyl-donor (MD) diet can modify DNA methylation at select murine genom...

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

Measured Environmental Contributions to Cannabis Abuse/Dependence in an Offspring of Twins Design

PubMed Central

Scherrer, Jeffrey F.; Grant, Julia D.; Duncan, Alexis E.; Pan, Hui; Waterman, Brian; Jacob, Theodore; Haber, Jon Randolph; True, William R.; Heath, Andrew C.; Bucholz, Kathleen Keenan

2008-01-01

Genetic and environmental factors are known to contribute to cannabis abuse/dependence (CAD). We sought to determine the magnitude of the contribution from measured environmental variables to offspring cannabis dependence in a design that controls for familial vulnerability. Data come from a study of 725 twin members of the Vietnam Era Twin Registry, 720 of their biological offspring (age 18–32 years) and 427 mothers. Data were obtained on offspring perception of family and peer support and substance use behaviors and offspring CAD. After adjusting for familial risk, and environmental covariates, CAD was significantly more likely among male offspring (OR=2.73; 95% CI: 1.69–4.41). Offspring CAD was associated with reporting: siblings used illicit drugs (OR=3.40; 95%CI:1.81–6.38), a few friends used drugs (OR=2.72; 95%CI: 1.04–7.09), a quarter or more friends used drugs (OR=8.30; 95% CI:3.09–22.33) and one-half or more 12th grade peers used drugs (OR=3.17; 95%CI: 1.42–7.08). Perceived sibling, friend and school peer substance use are strongly associated with CAD in young adults even after accounting for latent familial risk and for multiple measured intra-family and extra-family environmental influences. PMID:18583065

Gender-Dependent Effects of Maternal Immune Activation on the Behavior of Mouse Offspring

PubMed Central

Xuan, Ingrid C. Y.; Hampson, David R.

2014-01-01

Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the “maternal immune activation” model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior. PMID:25111339

Epigenetic Patterns Modulate the Connection Between Developmental Dynamics of Parenting and Offspring Psychosocial Adjustment.

PubMed

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 urban mother-offspring dyads. Mothers were assessed on their perceptions of maternal stress at each wave. Offspring were assessed on their perceptions of maternal parenting at each wave and on their adaptive and maladaptive behavior at the last wave. Genome-wide DNA methylation in peripheral T lymphocytes at the third wave was assayed using Methyl Binding Domain(MBD) sequencing. Statistically significant associations were identified between the change in offspring's perception of parenting from middle childhood to adulthood and the DNA methylation in offspring's adult genomes. Specifically, the slope of perceived parental rejection across the 3 time points was related to an increase in methylation, or a potential downregulation, of 565 genes thought to be involved in the control of a broad spectrum of biological functions generally related to cellular signaling. A subset of these epigenetic marks, clustered in 23 genes, some of which participate in the development and functioning of the CNS, were in turn associated with psychosocial adjustment as captured by interpersonal relationships and emotional self-evaluation. This appears to be one of the first investigations of the modulating role of the methylome in associations between developmental dynamics of parenting throughout the formative years of child and adolescent development and psychosocial adjustment in adulthood. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

The association between parental history of diagnosed mood/anxiety disorders and psychiatric symptoms and disorders in young adult offspring

PubMed Central

2012-01-01

Background Parental history of mood or anxiety disorders is one of the strongest and most consistent risk factors for the development of these disorders in offspring. Gaps remain however in our knowledge of whether maternal or paternal disorders are more strongly associated with offspring disorders, and whether the association exists in non-clinical samples. This study uses a large population-based sample to test if maternal or paternal history of mood and/or anxiety disorders increases the risk of mood and/or anxiety disorders, or symptoms of specific anxiety disorders, in offspring. Methods Data were drawn from the Nicotine Dependence in Teens Study, a prospective cohort investigation of 1293 grade 7 students. Data on mental health outcomes were collected in mailed self-report questionnaires when participants were aged 20.4 (0.7) years on average. Parental data were collected in mailed self-report questionnaires. This current analysis pertains to 564 participants with maternal and/or paternal data. The association between maternal and paternal history and each of diagnosed anxiety disorder, diagnosed mood disorder, and symptoms of specific anxiety disorders in offspring was studied in multivariate logistic regression. Results A higher proportion of mothers than fathers had a diagnosed mood/anxiety disorder (23% versus 12%). Similarly, 14% of female offspring had a diagnosed mood/anxiety disorder, compared to 6% of male offspring. The adjusted odds ratio (95% confidence interval) for maternal history was 2.2 (1.1, 4.5) for diagnosed mood disorders, 4.0 (2.1, 7.8) for diagnosed anxiety disorders, and 2.2 (1.2, 4.0) for social phobia symptoms. Paternal history was not associated with any of the mental health outcomes in offspring. Conclusion Maternal, but not paternal mood/anxiety disorders were associated with diagnosed psychiatric disorders, as well as symptoms of specific anxiety disorders, in offspring. Efforts to detect mood and anxiety disorders in offspring

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

Dietary Intake Influences Adult Fertility and Offspring Fitness in Zebrafish.

PubMed

Newman, Trent; Jhinku, Noel; Meier, Michael; Horsfield, Julia

2016-01-01

The burden of malnutrition, including both over- and undernutrition, is a major public health concern. Here we used a zebrafish model of diet-induced obesity to analyze the impact of dietary intake on fertility and the phenotype of the next generation. Over an eight-week period, one group received 60 mg of food each day (60 mg arm), while another received 5 mg (5 mg arm). At the end of the diet, the body mass index of the 60 mg arm was 1.5 fold greater than the 5 mg arm. The intervention also had a marked impact on fertility; breeding success and egg production in the 60 mg arm were increased 2.1- and 6.2-fold compared to the 5 mg arm, respectively. Transcriptome analysis of eggs revealed that transcripts involved in metabolic biological processes differed according to dietary intake. The progeny from the differentially fed fish were more likely to survive when the parents had access to more food. An intergenerational crossover study revealed that while parental diet did not influence weight gain in the offspring, the progeny of well-fed parents had increased levels of physical activity when exposed again to high nutrient availability. We conclude that dietary intake has an important influence on fertility and the subsequent fitness of offspring, even prior to breeding.

Dietary Intake Influences Adult Fertility and Offspring Fitness in Zebrafish

PubMed Central

Jhinku, Noel; Meier, Michael; Horsfield, Julia

2016-01-01

The burden of malnutrition, including both over- and undernutrition, is a major public health concern. Here we used a zebrafish model of diet-induced obesity to analyze the impact of dietary intake on fertility and the phenotype of the next generation. Over an eight-week period, one group received 60 mg of food each day (60 mg arm), while another received 5 mg (5 mg arm). At the end of the diet, the body mass index of the 60 mg arm was 1.5 fold greater than the 5 mg arm. The intervention also had a marked impact on fertility; breeding success and egg production in the 60 mg arm were increased 2.1- and 6.2-fold compared to the 5 mg arm, respectively. Transcriptome analysis of eggs revealed that transcripts involved in metabolic biological processes differed according to dietary intake. The progeny from the differentially fed fish were more likely to survive when the parents had access to more food. An intergenerational crossover study revealed that while parental diet did not influence weight gain in the offspring, the progeny of well-fed parents had increased levels of physical activity when exposed again to high nutrient availability. We conclude that dietary intake has an important influence on fertility and the subsequent fitness of offspring, even prior to breeding. PMID:27870856

Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

PubMed

Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

2017-01-16

Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

PubMed Central

Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

2017-01-01

Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Methods: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Conclusions: Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with

Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner.

PubMed

Bolton, Jessica L; Smith, Susan H; Huff, Nicole C; Gilmour, M Ian; Foster, W Michael; Auten, Richard L; Bilbo, Staci D

2012-11-01

Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pregnant mice were exposed to filtered air (FA) or diesel exhaust (DE) on embryonic days (E) 9-17. Prenatal DE induced a significant fetal brain cytokine response at E18 (46-390% over FA). As adults, offspring were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 6 wk. Adult DE male offspring weighed 12% more and were 35% less active than FA male offspring at baseline, whereas there were no differences in females. Following HFD, DE males gained weight at the same rate as FA males, whereas DE females gained 340% more weight than FA females. DE-HFD males had 450% higher endpoint insulin levels than FA-HFD males, and all males on HFD showed decreased activity and increased anxiety, whereas females showed no differences. Finally, both DE males and females fed HFD showed increased microglial activation (30-66%) within several brain regions. Thus, prenatal air pollution exposure can "program" offspring for increased susceptibility to diet-induced weight gain and neuroinflammation in adulthood in a sex-specific manner.

Effects of the murine skull in optoacoustic brain microscopy.

PubMed

Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

2016-01-01

Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Maternal natal environment and breeding territory predict the condition and sex ratio of offspring.

PubMed

Bowers, E Keith; Thompson, Charles F; Sakaluk, Scott K

2017-03-01

Females in a variety of taxa adjust offspring sex ratios to prevailing ecological conditions. However, little is known about whether conditions experienced during a female's early ontogeny influence the sex ratio of her offspring. We tested for past and present ecological predictors of offspring sex ratios among known-age females that were produced as offspring and bred as adults in a population of house wrens. The body condition of offspring that a female produced and the proportion of her offspring that were male were negatively correlated with the size of the brood in which she herself was reared. The proportion of sons within broods was negatively correlated with maternal hatching date, and varied positively with the quality of a female's current breeding territory as predicted. However, females producing relatively more sons than daughters were less likely to return to breed in the population the following year. Although correlative, our results suggest that the rearing environment can have enduring effects on later maternal investment and sex allocation. Moreover, the overproduction of sons relative to daughters may increase costs to a female's residual reproductive value, constraining the extent to which sons might be produced in high-quality breeding conditions. Sex allocation in birds remains a contentious subject, largely because effects on offspring sex ratios are small. Our results suggest that offspring sex ratios are shaped by various processes and trade-offs that act throughout the female life history and ultimately reduce the extent of sex-ratio adjustment relative to classic theoretical predictions.

DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.

PubMed

Fish, Trevor J; Benninghoff, Abby D

2017-11-01

Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and are suspected lung carcinogens in humans. Moreover, evidence from cell-based studies points to PAHs as modulators of the epigenome. The objective of this work was to assess patterns of genome-wide DNA methylation in lung tissues of adult offspring initiated in utero with the transplacental PAH carcinogens dibenzo [def,p]chrysene (DBC) or benzo [a]pyrene (BaP). Genome-wide methylation patterns for normal (not exposed), normal adjacent and lung tumor tissues obtained from adult offspring were determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen mouse DNA methylation CpG island array. Lung tumor incidence in 45-week old mice initiated with BaP was 32%, much lower than that of the DBC-exposed offspring at 96%. Also, male offspring appeared more susceptible to BaP as compared to females. Distinct patterns of DNA methylation were associated with non-exposed, normal adjacent and adenocarcinoma lung tissues, as determined by principal components, hierarchical clustering and gene ontology analyses. From these methylation profiles, a set of genes of interest was identified that includes potential important targets for epigenetic modification during the process of lung tumorigenesis in animals exposed to environmental PAHs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Intrauterine programming of lipid metabolic alterations in the heart of the offspring of diabetic rats is prevented by maternal diets enriched in olive oil.

PubMed

Capobianco, Evangelina; Pelesson, Magalí; Careaga, Valeria; Fornes, Daiana; Canosa, Ivana; Higa, Romina; Maier, Marta; Jawerbaum, Alicia

2015-10-01

Maternal diabetes can program metabolic and cardiovascular diseases in the offspring. The aim of this work was to address whether an olive oil supplemented diet during pregnancy can prevent lipid metabolic alterations in the heart of the offspring of mild diabetic rats. Control and diabetic Wistar rats were fed during pregnancy with either a standard diet or a 6% olive oil supplemented diet. The heart of adult offspring from diabetic rats showed increases in lipid concentrations (triglycerides in males and phospholipids, cholesterol, and free fatty acids in females), which were prevented with the maternal diets enriched in olive oil. Maternal olive oil supplementation increased the content of unsaturated fatty acids in the hearts of both female and male offspring from diabetic rats (possibly due to a reduction in lipoperoxidation), increased the expression of Δ6 desaturase in the heart of male offspring from diabetic rats, and increased the expression of peroxisome proliferator activated receptor α in the hearts of both female and male offspring from diabetic rats. Relevant alterations in cardiac lipid metabolism were evident in the adult offspring of a mild diabetic rat model, and regulated by maternal diets enriched in olive oil. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Egg-laying environment modulates offspring responses to predation risk in an amphibian.

PubMed

Tóth, Zoltán; Hettyey, Attila

2018-05-01

Predator-induced plasticity has been in the focus of evolutionary ecological research in the last decades, but the consequences of temporal variation in the presence of cues predicting offspring environment have remained controversial. This is partly due to the fact that the role of early environmental effects has scarcely been scrutinized in this context while also controlling for potential maternal effects. In this study, we investigated how past environmental conditions, that is different combinations of risky or safe adult (prenatal) and oviposition (early post-natal) environments, affected offspring's plastic responses in hatching time and locomotor activity to predation risk during development in the smooth newt (Lissotriton vulgaris). We found that females did not adjust their reproductive investment to the perceived level of risk in the adult environment, and this prenatal environment had generally negligible effect on offspring phenotype. However, when predator cues were absent during oviposition, larvae raised in the presence of predator cues delayed their hatching and exhibited a decreased activity compared to control larvae developing without predator cues, which responses are advantageous when predators pose a threat to hatched larvae. In the presence of predator cues during oviposition, the difference in hatching time persisted, but the difference in general locomotor activity disappeared between risk-exposed and control larvae. Our findings provide clear experimental evidence that fine-scale temporal variation in a predictive cue during and after egg-laying interactively affects offspring phenotype, and highlight the importance of the early post-natal environment, which may exert a substantial influence on progeny's phenotype also under natural conditions. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

Decline in offspring viability as a manifestation of aging in Drosophila melianogaster.

PubMed

Kern, S; Ackermann, M; Stearns, S C; Kawecki, T J

2001-09-01

The evolutionary explanation of senescence proposes that selection against alleles with deleterious effects manifested only late in life is weak because most individuals die earlier for extrinsic reasons. This argument also applies to alleles whose deleterious effects are nongenetically transmitted from mother to progeny, that is, that affect the performance of progeny produced at late ages rather than of the aging individuals themselves. We studied the effect of maternal age on offspring viability (egg hatching success and larva-to-adult survival) in two sets of Drosophila melanogaster lines (HAM/LAM and YOUNG/OLD), originating from two long-term selection experiments. In each set, some lines (HAM and YOUNG, respectively) have been selected for early reproduction, whereas later reproduction was favored in their counterparts (LAM and OLD). In the HAM and LAM lines, both egg hatching success and larval viability declined with mother's age and did so with accelerating rates. The hatching success declined significantly faster with maternal age in HAM than in LAM lines, according to one of two statistical approaches used. Egg hatching success also declined with maternal age in YOUNG and OLD lines, with no difference between the selection regimes. However, the relationship between mother's age and offspring larva-to-adult viability differed significantly between these two selection regimes: a decline of larval viability with maternal age occurred in YOUNG lines but not in OLD lines. This suggests that the rate with which offspring viability declines with mother's age responded to selection for early versus late reproduction. We suggest broadening the evolutionary concept of senescence to include intrinsically caused declines in offspring quality with maternal age.

Long-term consequences for offspring of paternal diabetes and metabolic syndrome.

PubMed

Linares Segovia, Benigno; Gutiérrez Tinoco, Maximiliano; Izquierdo Arrizon, Angeles; Guízar Mendoza, Juan Manuel; Amador Licona, Norma

2012-01-01

Recent studies have reported an increase in the prevalence of obesity and metabolic syndrome in children and adolescents. However, few have focused how diabetes mellitus and metabolic syndrome together in parents can influence on obesity and metabolic disturbances in offspring. To know the risk obesity and metabolic disturbance in children, adolescents, and young adults whose parents have diabetes mellitus and metabolic syndrome. A comparative survey was made in healthy children of parents with diabetes mellitus and metabolic syndrome compared with offspring of healthy parents. We performed anthropometry and evaluated blood pressure, glucose, total cholesterol, HDL cholesterol, and triglycerides levels in plasma. We registered parent antecedents to diabetes mellitus and metabolic syndrome and investigated the prevalence of overweight, obesity, and metabolic disturbances in offspring. We studied 259 subjects of 7 to 20 years of age. The prevalence of overweight and obesity was 27% and 37%, respectively. The highest proportion of BMI >95th of the entire group was found in offspring with both diabetic parents. Glucose and total cholesterol levels were lower in the group with healthy parents compared with the group with diabetic mother and metabolic syndrome but with healthy father. HDL cholesterol was higher in the group with both healthy parents than in the group with diabetic mother and metabolic syndrome but healthy father. The offspring of parents with diabetes plus metabolic syndrome showed higher proportion of variables related to metabolic syndrome compared with healthy parents.

Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

PubMed Central

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

2011-01-01

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

PubMed

Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

2012-12-01

Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 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. 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. 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.

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

Parent-offspring correlations in pedometer-assessed physical activity.

PubMed

Jacobi, David; Caille, Agnès; Borys, Jean-Michel; Lommez, Agnès; Couet, Charles; Charles, Marie-Aline; Oppert, Jean-Michel

2011-01-01

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. 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. 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). Ambulatory activity correlated within families, with a possible mother effect. Mother-offspring correlations remained significant through the transition from childhood to

Unexpected Long-Term Protection of Adult Offspring Born to High-Fat Fed Dams against Obesity Induced by a Sucrose-Rich Diet

PubMed Central

Couvreur, Odile; Ferezou, Jacqueline; Gripois, Daniel; Serougne, Colette; Crépin, Delphine; Aubourg, Alain; Gertler, Arieh; Vacher, Claire-Marie; Taouis, Mohammed

2011-01-01

Background Metabolic and endocrine environment during early life is crucial for metabolic imprinting. When dams were fed a high fat diet (HF diet), rat offspring developed hypothalamic leptin resistance with lean phenotype when weaned on a normal diet. Interestingly, when grown on the HF diet, they appeared to be protected against the effects of HF diet as compared to offspring of normally fed dams. The mechanisms involved in the protective effect of maternal HF diet are unclear. Methodology/Principal Findings We thus investigated the impact of maternal high fat diet on offspring subjected to normal or high palatable diet (P diet) on metabolic and endocrine parameters. We compared offspring born to dams fed P or HF diet. Offspring born to dams fed control or P diet, when fed P diet exhibited a higher body weight, altered hypothalamic leptin sensitivity and metabolic parameters suggesting that maternal P diet has no protective effect on offspring. Whereas, maternal HF diet reduces body weight gain and circulating triglycerides, and ameliorates corpulence index of offspring, even when subjected to P diet. Interestingly, this protective effect is differently expressed in male and female offspring. Male offspring exhibited higher energy expenditure as mirrored by increased hypothalamic UCP-2 and liver AdipoR1/R2 expression, and a profound change in the arcuate nucleus astrocytic organization. In female offspring, the most striking impact of maternal HF diet is the reduced hypothalamic expression of NPY and POMC. Conclusions/Significance HF diet given during gestation and lactation protects, at least partially, offspring from excessive weight gain through several mechanisms depending upon gender including changes in arcuate nucleus astrocytic organization and increased hypothalamic UCP-2 and liver AdipoR1/2 expression in males and reduced hypothalamic expression of NPY and POMC in females. Taken together our results reveal new mechanisms involved in the protective

Early decrease of insulin sensitivity in offspring of individuals with type 2 diabetes. The Mexican Diabetes Prevention Study.

PubMed

Pérez-Fuentes, Ricardo; Baez-Duarte, Blanca G; Zamora-Ginez, Irma; Ruiz-Vivanco, Guadalupe; Pulido-Pérez, Patricia; Nieva-Vázquez, Adriana; Gonzalez-Mejia, M Elba; Torres-Rasgado, Enrique

2014-04-01

Defects in insulin sensitivity (IS) and insulin secretion have been recognized as risk factors for type 2 diabetes (T2D) and its complications. We undertook this study to establish the relationship between healthy type 2 diabetic offspring (OFD) from a Mexican population with IS. A total of 602 Mexican subjects, 359 first-degree offspring of T2D (OFD+) and 243 first-degree non-offspring of T2D (OFD-) were classified as young adults (age range, 18-44 years) and middle-aged adults (age range, 45-65 years). Groups were clinically and biochemically characterized. Quantitative insulin sensitivity check index (QUICKI) was used to estimate IS and the homeostasis model assessment B (HOMA-B) was used to estimate B cell function. IS decreased significantly (p <0.05) in OFD+ middle-aged (QUICKI 0.330 ± 0.03) compared with OFD- (0. 370 ± 0.03). Middle-aged adults (OFD+) had the highest prevalence of increased fasting insulin levels (FIL) (13.6%) and decreased IS (22.9%) compared with OFD- groups (3.2%). A binary regression analysis showed the association of OFD+ with increased FIL (odds ratio [OR], 3.71; 95% confidence interval [95% CI], 1.68-8.2; p = 0.001), and QUICKI (OR, 10.87; 95% CI, 2.36-44.69; p <0.01) adjusted by gender, age, and obesity. Our results suggest that decreased IS itself could be recognized as one of the earliest detectable abnormalities in middle-aged adults. Moreover, prevalence increases with age and is associated with type 2 diabetic offspring, regardless of obesity. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

Gestational N-hexane inhalation alters the expression of genes related to ovarian hormone production and DNA methylation states in adult female F1 rat offspring.

PubMed

Li, Hong; Zhang, Chenyun; Ni, Feng; Guo, Suhua; Wang, Wenxiang; Liu, Jing; Lu, Xiaoli; Huang, Huiling; Zhang, Wenchang

2015-12-15

Research has revealed that n-hexane can disrupt adult female endocrine functions; however, few reports have focused on endocrine changes in adult F1 females after maternal exposure during gestation. In this study, female Wistar rats inhaled 100, 500, 2500, or 12,500 ppm n-hexane for 4 h daily during their initial 20 gestational days. The F1 female offspring exhibited abnormal oestrus cycles. Compared with the controls, the in vitro-cultured ovarian granulosa cells of the 12,500 ppm group showed significantly reduced in vitro progesterone and oestradiol secretion. Elevated progesterone secretion was observed in the 500 ppm group, and decreased and significantly upregulated mRNA expression of the Star, Cyp11a1, Cyp17a1, and Hsd3b genes was observed in the 12,500 ppm and 500 ppm groups, respectively. The protein expression levels were consistent with the mRNA expression levels. Methylation screening of the promoter regions of these genes was performed using MeDIP-chip and confirmed by methylation-sensitive high-resolution melting (MS-HRM), and the observed methylation state changes of the promoter regions were correlated with the gene expression levels. The results suggest that the hormone levels in the female offspring after gestational n-hexane inhalation correspond to the expression levels and DNA methylation states of the hormone production genes. Copyright © 2015. Published by Elsevier Ireland Ltd.

Genetic and environmental influences on the familial transmission of externalizing disorders in adoptive and twin offspring.

PubMed

Hicks, Brian M; Foster, Katherine T; Iacono, William G; McGue, Matt

2013-10-01

Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects. To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission. Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences. Participants were recruited from the community and assessed at a university laboratory. A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years). Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. RESULTS There was a medium effect for the transmission of the general externalizing liability for biological parents (r = 0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (r = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a2 = 0.61) but also exhibited significant shared environmental influences (c2 = 0.20). Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines.

PubMed

McBride, Shawna M; Culver, Bruce; Flynn, Francis W

2006-10-01

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

PubMed Central

Glastras, Sarah J.; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T.; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A.; Saad, Sonia

2017-01-01

Aims/Hypothesis Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Methods Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. Results HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Conclusion Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity. PMID:28225809

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.

PubMed

Glastras, Sarah J; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A; Saad, Sonia

2017-01-01

Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

Sex dimorphism in late gestational sleep fragmentation and metabolic dysfunction in offspring mice.

PubMed

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

2015-04-01

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. 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. 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. 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. © 2015 Associated Professional Sleep Societies, LLC.

Parents' perceptions on offspring risk and prevention of anxiety and depression: a qualitative study.

PubMed

Festen, Helma; Schipper, Karen; de Vries, Sybolt O; Reichart, Catrien G; Abma, Tineke A; Nauta, Maaike H

2014-01-01

Offspring of patients with anxiety or depression are at high risk for developing anxiety or depression. Despite the positive findings regarding effectiveness of prevention programs, recruitment for prevention activities and trials is notoriously difficult. Our randomized controlled prevention trial was terminated due to lack of patient inclusion. Research on mentally-ill parents' perceptions of offspring's risk and need for preventive intervention may shed light on this issue, and may enhance family participation in prevention activities and trials. Qualitative data were collected through semi-structured interviews with 24 parents (patients with anxiety or depression, or their partners). An inductive content analysis of the data was performed. Five research questions were investigated regarding parents' perceptions of anxiety, depression, and offspring risk; anxiety, depression, and parenting; the need for offspring intervention and prevention; and barriers to and experiences with participation in preventive research. Parental perceptions of the impact of parental anxiety and depression on offspring greatly differed. Parents articulated concerns about children's symptomatology, however, most parents did not perceive a direct link between parent symptoms and offspring quality of life. They experienced an influence of parental symptoms on family quality of life, but chose not to discuss that with their children in order to protect them. Parents were not well aware of the possibilities regarding professional help for offspring and preferred parent-focused rather than offspring-focused interventions such as parent psycho-education. Important barriers to participation in preventive research included parental overburden, shame and stigma, and perceived lack of necessity for intervention. This study highlights the importance of educating parents in adult health care. Providing psycho-education regarding offspring risk, communication in the family, and parenting in order

Transmission of two Australian strains of murine cytomegalovirus (MCMV) in enclosure populations of house mice (Mus domesticus).

PubMed

Farroway, L N; Gorman, S; Lawson, M A; Harvey, N L; Jones, D A; Shellam, G R; Singleton, G R

2005-08-01

To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.

Gestational low-protein intake enhances whole-kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in rat adult male offspring.

PubMed

Sene, Letícia B; Rizzi, Victor Hugo Gonçalves; Gontijo, José A R; Boer, Patricia A

2018-05-22

Studies have shown that adult offspring of mothers fed a protein-restricted diet during pregnancy present a pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Additionally, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation and inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as a common factor. In the current study, protein and sodium urinary excretion rates were evaluated in rats, and immunohistochemistry and western blot techniques were used to characterize kidney structure changes in 16 week old male offspring of mothers fed a low-protein diet during pregnancy (LP group) compared with age-matched (NP) controls. We also verified the expression of miRNA, mRNA and protein markers of fibrosis and the EMT in whole kidney prepared from LP offspring. We found, surprisingly, that arterial hypertension and long-term hyperfiltration, manifest by proteinuria, were associated with increased renal miR-192 and miR-200 family expression in 16 week old LP relative to age-matched NP rats. Measurement of kidney fibrosis and EMT-related protein markers, by histochemistry and immunoblot techniques, showed a significant rise of TGF-β1 and type-I collagen content in glomeruli and tubulointerstitial areas, accompanied by enhanced fibronectin and ZEB1 and decreased E-cadherin immunoreactivity in 16 week old LP offspring. The results were partially confirmed by increased gene (mRNA) expression of collagen 1α1, collagen 1α2 and ZEB1 in LP whole kidneys compared with those of age-matched NP offspring. In view of the presumed functional overload in the remaining nephrons, we suggest that hypertension and proteinuria development following maternal protein restriction may be a preponderant factor for EMT and

A maternal "junk-food" diet reduces sensitivity to the opioid antagonist naloxone in offspring postweaning.

PubMed

Gugusheff, Jessica R; Ong, Zhi Yi; Muhlhausler, Beverly S

2013-03-01

Perinatal exposure to a maternal "junk-food" diet has been demonstrated to increase the preference for palatable diets in adult offspring. We aimed to determine whether this increased preference could be attributed to changes in μ-opioid receptor expression within the mesolimbic reward pathway. We report here that mRNA expression of the μ-opioid receptor in the ventral tegmental area (VTA) at weaning was 1.4-fold (males) and 1.9-fold (females) lower in offspring of junk-food (JF)-fed rat dams than in offspring of dams fed a standard rodent diet (control) (P<0.05). Administration of the opioid antagonist naloxone to offspring given a palatable diet postweaning significantly reduced fat intake in control offspring (males: 7.7 ± 0.7 vs. 5.4 ± 0.6 g/kg/d; females: 6.9 ± 0.3 vs. 3.9 ± 0.5 g/kg/d; P<0.05), but not in male JF offspring (8.6 ± 0.6 vs. 7.1 ± 0.5 g/kg/d) and was less effective at reducing fat intake in JF females (42.2 ± 6.0 vs. 23.1 ± 4.1% reduction, P<0.05). Similar findings were observed for total energy intake. Naloxone treatment did not affect intake of standard rodent feed in control or JF offspring. These findings suggest that exposure to a maternal junk-food diet results in early desensitization of the opioid system which may explain the increased preference for junk food in these offspring.

Comparing indicators of health and development of singleton young adults conceived with and without assisted reproductive technology.

PubMed

Halliday, Jane; Wilson, Cate; Hammarberg, Karin; Doyle, Lex W; Bruinsma, Fiona; McLachlan, Robert; McBain, John; Berg, Turi; Fisher, Jane R; Amor, David

2014-04-01

To compare outcomes for young adults conceived by assisted reproductive technology (ART) with non-ART-conceived young adults. Cohort study. Not applicable. Mothers and their offspring (aged 18-28 years) conceived by ART; mothers and their non-ART-conceived offspring, randomly selected from the same source population. Structured telephone interviews, one with mothers and another with their young adult offspring. Maternal report on young adult offspring hospitalizations and chronic illness accumulated over the first 18 years of their lives; young adult self-report on perceived current quality of life, body mass index, pubertal development, and educational achievement. Of 1,480 eligible ART mothers, 80% were traced and contacted. Of those, 656 (55%) participated, reporting on 705 ART-conceived offspring; 269 (23%) declined participation and 262 (22%) did not respond. Of the participants, 84% consented to contact with their young adult offspring, of whom 547 (92%) participated. Random-digit dialing recruited 868 non-ART mothers and 549 offspring. Compared with non-ART young adults, the ART group had significant increases in three maternally reported outcomes: 1) hospital admissions, including those in the secondary school years; 2) atopic respiratory conditions; and 3) combined endocrine, nutritional, and metabolic disease ICD-10 category. Young adult reported outcomes were similar for both groups. This study addresses gaps in knowledge of outcomes beyond adolescence for those conceived by ART. Results show few adverse outcomes in this large cohort of young adults, but additional assessment through clinical review is required to address issues unable to be examined in this study. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Long-Term Survival of Photoreceptors Transplanted into the Adult Murine Neural Retina Requires Immune Modulation

PubMed Central

West, Emma L.; Pearson, Rachael A.; Barker, Susie E.; Luhmann, Ulrich F. O.; Maclaren, Robert E.; Barber, Amanda C.; Duran, Yanai; Smith, Alexander J.; Sowden, Jane C.; Ali, Robin R.

2012-01-01

Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp+ve photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective. PMID:20857496

Maternal consumption of a high-meat, low-carbohydrate diet in late pregnancy: relation to adult cortisol concentrations in the offspring.

PubMed

Herrick, Kirsten; Phillips, David I W; Haselden, Soraya; Shiell, Alistair W; Campbell-Brown, Mary; Godfrey, Keith M

2003-08-01

Recent studies have linked maternal consumption of an unbalanced high-protein, low-carbohydrate diet in late pregnancy with raised adult blood pressure in the offspring. Because high-protein diets stimulate the hypothalamic-pituitary-adrenal axis, we hypothesized that an unbalanced maternal diet might increase maternal cortisol levels, exposing the fetus to excess cortisol and programming lifelong hypersecretion of cortisol. We therefore measured fasting plasma cortisol concentrations in 251 subjects, 28-30 yr old, whose mothers had been advised to eat 0.45 kg of red meat daily during pregnancy and avoid carbohydrate-rich foods. Cortisol concentrations were higher in subjects with lower body mass index (P < 0.0001) and in those who reported recent vigorous activity (P = 0.03) and greater alcohol consumption (P = 0.004). Allowing for gender, current body mass index, activity, and alcohol consumption, cortisol concentrations increased 5.4% per portion of maternal meat/fish consumption per day (P = 0.03), decreased 3.3% per portion of maternal green vegetable consumption per week (P = 0.14), and were 12.2% higher in those born into manual social class families (P = 0.03). The specific advice given to mothers in this study precludes direct application to other populations, but the findings provide the first human evidence that an unbalanced maternal diet during late pregnancy may program lifelong hypercortisolemia in the offspring.

Dietary Glycemic Index during Pregnancy Is Associated with Biomarkers of the Metabolic Syndrome in Offspring at Age 20 Years

PubMed Central

Danielsen, Inge; Granström, Charlotta; Haldorsson, Thorhallur; Rytter, Dorte; Hammer Bech, Bodil; Henriksen, Tine Brink; Vaag, Allan Arthur; Olsen, Sjurdur Frodi

2013-01-01

Objective Growing evidence indicates that metabolic syndrome is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the study was to assess the possible associations between the dietary glycemic index (GI) and glycemic load (GL) during pregnancy and biomarkers of the metabolic syndrome in young adult offspring. Methods Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 428 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI), education, energy intake, and the offspring’s ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account. Outcome Measures Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR) and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring. Results Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units’ GI increase was 1.09 [95% CI: 1.01, 1.16], p = 0.02), insulin (1.09 [95% CI: 1.02, 1.16], p = 0.01) and leptin (1.21 [95% CI: 1.06, 1.38], p = 0.01) in the offspring; whereas no associations were detected for GL. Conclusions Our data suggests that high dietary GI in pregnancy may affect levels of markers for the metabolic syndrome in young adult offspring in a potentially harmful direction. PMID:23741411

Paternal obesity, interventions, and mechanistic pathways to impaired health in offspring.

PubMed

McPherson, Nicole O; Fullston, Tod; Aitken, R John; Lane, Michelle

2014-01-01

The global rates of male overweight/obesity are rising, approaching 70% of the total adult population in Western nations. Overweight/obesity increases the risk of chronic diseases; however, there is increasing awareness that male obesity negatively impacts fertility, subsequent pregnancy, and the offspring health burden. Developmental programming is well defined in mothers; however, it is becoming increasingly evident that developmental programming can be paternally initiated and mediated through paternal obesity. Both human and rodent models have established that paternal obesity impairs sex hormones, basic sperm function, and molecular composition. This results in perturbed embryo development and health and an increased subsequent offspring disease burden in both sexes. The reversibility of obesity-induced parental programming has only recently received attention. Promising results in animal models utilizing diet and exercise interventions have shown improvements in sperm function and molecular composition, resulting in restorations of both embryo and fetal health and subsequent male offspring fertility. The direct mode for paternal inheritance is likely mediated via spermatozoa. We propose two main theories for the origin of male obesity-induced paternal programming: (1) accumulation of sperm DNA damage resulting in de novo mutations in the embryo and (2) changes in sperm epigenetic marks (microRNA, methylation, or acetylation) altering the access, transcription, and translation of paternally derived genes during early embryogenesis. Paternal overweight/obesity induces paternal programming of offspring phenotypes likely mediated through genetic and epigenetic changes in spermatozoa. These programmed changes to offspring health appear to be partially restored via diet/exercise interventions in obese fathers preconception, which have been shown to improve aspects of sperm DNA integrity. However, the majority of data surrounding paternal obesity and offspring

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

PubMed

Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

2016-09-01

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. 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. 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. 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.

Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

PubMed

Oliveira, V; Silva Junior, S D; de Carvalho, M H C; Akamine, E H; Michelini, L C; Franco, M C

2017-04-01

It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

The influence of parents' religious practices on young adults' divorce attitudes.

PubMed

Kapinus, Carolyn A; Pellerin, Lisa A

2008-09-01

This study investigates the intergenerational transmission of parents' religious views and divorce attitudes, paying particular attention to the effect of parent-child closeness. We use structural equation modeling to examine a national longitudinal data set containing information from 455 married individuals and their adult offspring. We find that parent religiosity influences young adults' views of divorce via two pathways: by affecting offspring's religiosity and parents' views of divorce. More religious offspring are less tolerant of divorce, but offspring who do not share their parents' religious practices are nonetheless influenced by their parents' religiously-influenced divorce attitudes. While parent religiosity has no effect on parent-child closeness, religious offspring report having been closer to their parents, suggesting that their current religious practices may affect their perceptions of the parent-child relationship.

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

Psychopathology in adolescent offspring of parents with panic disorder, major depression, or both: a 10-year follow-up.

PubMed

Hirshfeld-Becker, Dina R; Micco, Jamie A; Henin, Aude; Petty, Carter; Faraone, Stephen V; Mazursky, Heather; Bruett, Lindsey; Rosenbaum, Jerrold F; Biederman, Joseph

2012-11-01

The authors examined the specificity and course of psychiatric disorders from early childhood through adolescence in offspring of parents with confirmed panic disorder and major depressive disorder. The authors examined rates of psychiatric disorders at 10-year-follow-up (mean age, 14 years) in four groups: offspring of referred parents with panic and depression (N=137), offspring of referred parents with panic without depression (N=26), offspring of referred parents with depression without panic (N=48), and offspring of nonreferred parents with neither disorder (N=80). Follow-up assessments relied on structured interviews with the adolescents and their mothers; diagnoses were rated present if endorsed by either. Parental panic disorder, independently of parental depression, predicted lifetime rates in offspring of multiple anxiety disorders, panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Parental depression independently predicted offspring bipolar, drug use, and disruptive behavior disorders. Parental panic and depression interacted to predict specific phobia and major depressive disorder. Phobias were elevated in all at-risk groups, and depression was elevated in both offspring groups of parents with depression (with or without panic disorder), with the highest rates in the offspring of parents with depression only. Parental depression independently predicted new onset of depression, parental panic disorder independently predicted new onset of social phobia, and the two interacted to predict new onset of specific phobia and generalized anxiety disorder. At-risk offspring continue to develop new disorders as they progress through adolescence. These results support the need to screen and monitor the offspring of adults presenting for treatment of panic disorder or major depressive disorder.

Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

PubMed

Gautier, Yentl; Luneau, Isabelle; Coquery, Nicolas; Meurice, Paul; Malbert, Charles-Henri; Guerin, Sylvie; Kemp, Bas; Bolhuis, J Elizabeth; Clouard, Caroline; Le Huërou-Luron, Isabelle; Blat, Sophie; Val-Laillet, David

2018-06-13

This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure.

PubMed

Bierer, Linda M; Bader, Heather N; Daskalakis, Nikolaos P; Lehrner, Amy L; Makotkine, Iouri; Seckl, Jonathan R; Yehuda, Rachel

2014-10-01

Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-h urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. The inverse association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the directional effect on offspring will

Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure

PubMed Central

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

2014-01-01

Background Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Methods Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-hr urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Results Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. Conclusions The association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the

Maternal Exposure to the Holocaust and Health Complaints in Offspring

PubMed Central

Flory, Janine D.; Bierer, Linda M.; Yehuda, Rachel

2011-01-01

Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and self-reported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring’s own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved. PMID:21508517

Profiling and Validation of the Circular RNA Repertoire in Adult Murine Hearts.

PubMed

Jakobi, Tobias; Czaja-Hasse, Lisa F; Reinhardt, Richard; Dieterich, Christoph

2016-08-01

For several decades, cardiovascular disease has been the leading cause of death throughout all countries. There is a strong genetic component to many disease subtypes (e.g., cardiomyopathy) and we are just beginning to understand the relevant genetic factors. Several studies have related RNA splicing to cardiovascular disease and circular RNAs (circRNAs) are an emerging player. circRNAs, which originate through back-splicing events from primary transcripts, are resistant to exonucleases and typically not polyadenylated. Initial functional studies show clear phenotypic outcomes for selected circRNAs. We provide, for the first time, a comprehensive catalogue of RNase R-resistant circRNA species for the adult murine heart. This work combines state-of-the-art circle sequencing with our novel DCC software to explore the circRNA landscape of heart tissue. Overall, we identified 575 circRNA species that pass a beta-binomial test for enrichment (false discovery rate of 1%) in the exonuclease-treated sequencing sample. Several circRNAs can be directly attributed to host genes that have been previously described as associated with cardiovascular disease. Further studies of these candidate circRNAs may reveal disease-relevant properties or functions of specific circRNAs. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Maternal effects on offspring depend on female mating pattern and offspring environment in yellow dung flies.

PubMed

Tregenza, Tom; Wedell, Nina; Hosken, David J; Ward, Paul I

2003-02-01

Direct costs and benefits to females of multiple mating have been shown to have large effects on female fecundity and longevity in several species. However, with the exception of studies examining genetic benefits of polyandry, little attention has been paid to the possible effects on offspring of multiple mating by females. We propose that nongenetic effects of maternal matings on offspring fitness are best viewed in the same context as other maternal phenotype effects on offspring that are well known even in species lacking parental care. Hence, matings can exert effects on offspring in the same way as other maternal environment variables, and are likely to interact with such effects. We have conducted a study using yellow dung flies (Scathophaga stercoraria), in which we independently manipulated female mating rate, number of mates and maternal thermal environment and measured subsequent fecundity, hatching success, and offspring life-history traits. To distinguish between direct effects of matings and potential genetic benefits of polyandry we split broods and reared offspring at three different temperature regimes. This allowed us to demonstrate that although we could not detect any simple benefits or costs to matings, there are effects of maternal environment on offspring and these effects interact with female mating regime affecting offspring fitness. Such interactions between female phenotype and the costs and benefits of matings have potentially broad implications for understanding female behavior.

Investigation of implicit avoidance of displacement-related stimuli in offspring of trauma exposed, forcibly-displaced individuals.

PubMed

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

2017-04-01

There is an ongoing debate as to whether traumatization also affects the close relatives of trauma survivors who have symptoms of PTSD. Although many studies provide evidence favoring a transgenerational transmission, other studies have not found evidence to support this idea. The present study examined whether adult offspring of individuals exposed to trauma during forced displacement with (n=22) and without PTSD (n=24) exhibit an implicit avoidance of stimuli related to the parental trauma compared to children of non-trauma exposed control participants (n=23) using an Approach-Avoidance task (AAT). Offspring participants were requested to push (i.e., avoidance) or pull (i.e., approach) displacement-related and neutral pictures, whereby response direction depended on a non-affective dimension (color of the pictures). Results suggest that the offspring of non-PTSD participants exhibit implicit avoidance of displacement-related stimuli. This rather unexpected finding might either indicate resilience amongst offspring of PTSD participants or that offspring of non-PTSD participants are particularly affected. If these results were to replicate, they suggest that implicit avoidance tendencies amongst the offspring of trauma exposed participants might partially contribute to their heightened PTSD vulnerability. Longitudinal studies are needed to elucidate whether implicit avoidance tendencies are associated with increased stress vulnerability. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Vibrio parahaemolyticus ToxRS Regulator Is Required for Stress Tolerance and Colonization in a Novel Orogastric Streptomycin-Induced Adult Murine Model

PubMed Central

Whitaker, W. Brian; Parent, Michelle A.; Boyd, Aoife; Richards, Gary P.

2012-01-01

Vibrio parahaemolyticus, a marine bacterium, is the causative agent of gastroenteritis associated with the consumption of seafood. It contains a homologue of the toxRS operon that in V. cholerae is the key regulator of virulence gene expression. We examined a nonpolar mutation in toxRS to determine the role of these genes in V. parahaemolyticus RIMD2210633, an O3:K6 isolate, and showed that compared to the wild type, ΔtoxRS was significantly more sensitive to acid, bile salts, and sodium dodecyl sulfate stresses. We demonstrated that ToxRS is a positive regulator of ompU expression, and that the complementation of ΔtoxRS with ompU restores stress tolerance. Furthermore, we showed that ToxRS also regulates type III secretion system genes in chromosome I via the regulation of the leuO homologue VP0350. We examined the effect of ΔtoxRS in vivo using a new orogastric adult murine model of colonization. We demonstrated that streptomycin-treated adult C57BL/6 mice experienced prolonged intestinal colonization along the entire intestinal tract by the streptomycin-resistant V. parahaemolyticus. In contrast, no colonization occurred in non-streptomycin-treated mice. A competition assay between the ΔtoxRS and wild-type V. parahaemolyticus strains marked with the β-galactosidase gene lacZ demonstrated that the ΔtoxRS strain was defective in colonization compared to the wild-type strain. This defect was rescued by ectopically expressing ompU. Thus, the defect in stress tolerance and colonization in ΔtoxRS is solely due to OmpU. To our knowledge, the orogastric adult murine model reported here is the first showing sustained intestinal colonization by V. parahaemolyticus. PMID:22392925

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...

Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats

EPA Science Inventory

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be m...

Impact of maternal mild hyperglycemia on maternal care and offspring development and behavior of Wistar rats.

PubMed

Kiss, Ana Carolina Inhasz; Woodside, Barbara; Felício, Luciano Freitas; Anselmo-Franci, Janete; Damasceno, Débora Cristina

2012-10-10

The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity. Copyright © 2012 Elsevier Inc. All rights reserved.

The Evaluation of Folic Acid-Deficient or Folic Acid-Supplemented Diet in the Gestational Phase of Female Rats and in Their Adult Offspring Subjected to an Animal Model of Schizophrenia.

PubMed

Canever, L; Alves, C S V; Mastella, G; Damázio, L; Polla, J V; Citadin, S; De Luca, L A; Barcellos, A S; Garcez, M L; Quevedo, J; Budni, J; Zugno, A I

2018-03-01

Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were

Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

PubMed Central

Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

2015-01-01

Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

Both high and low maternal salt intake in pregnancy alter kidney development in the offspring.

PubMed

Koleganova, Nadezda; Piecha, Grzegorz; Ritz, Eberhard; Becker, Luis Eduardo; Müller, Annett; Weckbach, Monika; Nyengaard, Jens Randel; Schirmacher, Peter; Gross-Weissmann, Marie-Luise

2011-08-01

In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.

The Long-Term Effects of the Periconceptional Period on Embryo Epigenetic Profile and Phenotype; The Paternal Role and His Contribution, and How Males Can Affect Offspring's Phenotype/Epigenetic Profile.

PubMed

Lucas, Emma S; Watkins, Adam J

2017-01-01

The number of adults afflicted with heart disease, obesity and diabetes, central components of metabolic disorder, has grown rapidly in recent decades, affecting up to one quarter of the world's population. Typically, these diseases are attributed to lifestyle factors such as poor diet, lack of exercise and smoking. However, studies have now identified strong associations between patterns of growth during foetal and neonatal life and an increase predisposition towards developing heart disease, obesity and diabetes in adult life. While the connection between a mother's diet and the long-term health of her offspring has been studied in great detail, our understanding of whether offspring health might be affected by a father's diet remains limited. Greater insight into the impact that paternal nutrition has on sperm quality, epigenetic status and potential offspring programming mechanisms is needed to redress this parental-programming knowledge imbalance. Disturbances in paternal reproductive epigenetic status represents one key mechanism linking paternal diet with the programing of offspring development and adult health, as many enzymatic processes involved in epigenetic regulation use metabolic intermediates to modify DNA and histones. Here, poor paternal nutrition could result in perturbed sperm and testicular epigenetic status, impacting on post-fertilisation gene transcriptional regulation and protein expression in offspring tissues, resulting in increased incidences of metabolic disorder in adult life.

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.

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

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

Maternal smoking during pregnancy and offspring antisocial behaviour: findings from a longitudinal investigation of discordant siblings.

PubMed

Paradis, Angela D; Shenassa, Edmond D; Papandonatos, George D; Rogers, Michelle L; Buka, Stephen L

2017-09-01

Although many observational studies have found a strong association between maternal smoking during pregnancy (MSP) and offspring antisocial behaviour, the likelihood that this relationship is causal remains unclear. To comment on the potential causality of this association, the current investigation used a between-within decomposition approach to examine the association between MSP and multiple indices of adolescent and adult antisocial behaviour. Study participants were offspring of women enrolled in the Providence and Boston sites of the Collaborative Perinatal Project. Information on MSP was collected prospectively. Antisocial behaviour was assessed via self-report and through official records searches. A subset of the adult offspring (average age: 39.6 years) were enrolled in a follow-up study oversampling families with multiple siblings. Participants in this follow-up study self-reported on juvenile and adult antisocial behaviours during a structured interview (n=1684). Official records of juvenile (n=3447) and adult (n=3433) criminal behaviour were obtained for participants in the Providence cohort. Statistical models allowed between-family effects of MSP exposure to differ from within-family effects. In the absence of heterogeneity in between-family versus within-family estimates, a combined estimate was calculated. MSP was associated with a range of antisocial behaviours, measured by self-report and official records. For example, MSP was associated with increased odds of elevated levels of antisocial behaviours during adolescence and adulthood, as well as violent and non-violent outcomes during both developmental periods. Findings are consistent with a small-to-moderate causal effect of MSP on adolescent and adult antisocial behaviour. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of Periconception Cadmium and Mercury Co-Administration to Mice on Indices of Chronic Diseases in Male Offspring at Maturity

PubMed Central

Camsari, Cagri; Folger, Joseph K.; McGee, Devin; Bursian, Steven J.; Wang, Hongbing; Knott, Jason G.; Smith, George W.

2016-01-01

Background: Long-term exposure to the heavy metals cadmium (Cd) and mercury (Hg) is known to increase the risk of chronic diseases. However, to our knowledge, exposure to Cd and Hg beginning at the periconception period has not been studied to date. Objective: We examined the effect of Cd and Hg that were co-administered during early development on indices of chronic diseases in adult male mice. Methods: Adult female CD1 mice were subcutaneously administered a combination of cadmium chloride (CdCl2) and methylmercury (II) chloride (CH3HgCl) (0, 0.125, 0.5, or 2.0 mg/kg body weight each) 4 days before and 4 days after conception (8 days total). Indices of anxiety-like behavior, glucose homeostasis, endocrine and molecular markers of insulin resistance, and organ weights were examined in adult male offspring. Results: Increased anxiety-like behavior, impaired glucose homeostasis, and higher body weight and abdominal adipose tissue weight were observed in male offspring of treated females compared with controls. Significantly increased serum leptin and insulin concentrations and impaired insulin tolerance in the male offspring of dams treated with 2.0 mg/kg body weight of Cd and Hg suggested insulin resistance. Altered mRNA abundance for genes associated with glucose and lipid homeostasis (GLUT4, IRS1, FASN, ACACA, FATP2, CD36, and G6PC) in liver and abdominal adipose tissues as well as increased IRS1 phosphorylation in liver (Ser 307) provided further evidence of insulin resistance. Conclusions: Results suggest that the co-administration of Cd and Hg to female mice during the early development of their offspring (the periconception period) was associated with anxiety-like behavior, altered glucose metabolism, and insulin resistance in male offspring at adulthood. Citation: Camsari C, Folger JK, McGee D, Bursian SJ, Wang H, Knott JG, Smith GW. 2017. Effects of periconception cadmium and mercury co-administration to mice on indices of chronic diseases in male offspring

Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice

PubMed Central

Stack, Conor M.; Lim, Maria A.; Cuasay, Katrina; Stone, Madeleine M.; Seibert, Kimberly. M.; Spivak-Pohis, Irit; Crawley, Jacqueline N.; Waschek, James A.; Hill, Joanna M.

2008-01-01

Blockage of vasoactive intestinal peptide (VIP) receptors during early embryogenesis in the mouse has been shown to result in developmental delays in neonates, and social behavior deficits selectively in adult male offspring. Offspring of VIP deficient mothers (VIP +/−) also exhibited developmental delays, and reductions in maternal affiliation and play behavior. In the current study, comparisons among the offspring of VIP deficient mothers (VIP +/−) mated to VIP +/− males with the offspring of wild type (WT) mothers mated to VIP +/− males allowed assessment of the contributions of both maternal and offspring VIP genotype to general health measures, social behavior, fear conditioning, and spatial learning and memory in the water maze. These comparisons revealed few differences in general health among offspring of WT and VIP deficient mothers, and all offspring exhibited normal responses in fear conditioning and in the acquisition phase of spatial discrimination in the water maze. WT mothers produced offspring that were normal in all tests; the reduced VIP in their VIP +/− offspring apparently did not contribute to any defects in the measures under study. However, regardless of their own VIP genotype, all male offspring of VIP deficient mothers exhibited severe deficits in social approach behavior and reversal learning. The deficits in these behaviors in the female offspring of VIP deficient mothers were less severe than in their male littermates, and the extent of their impairment was related to their own VIP genotype. This study has shown that intrauterine conditions had a greater influence on behavioral outcome than did genetic inheritance. In addition, the greater prevalence of deficits in social behavior and the resistance to change seen in reversal learning in the male offspring of VIP deficient mothers indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders such as autism. PMID

Long-term influences of parental divorce on offspring affective disorders: A systematic review and meta-analysis.

PubMed

Sands, Amy; Thompson, Ellen J; Gaysina, Darya

2017-08-15

The prevalence of divorce in Western countries has increased in recent decades. However, there is no recent systematic review and/or meta-analysis of studies testing for long-term effects of parental divorce on offspring affective disorders. The present study conducted a systematic review and meta-analysis of studies published since 1980 testing for the association between parental divorce and offspring depression and anxiety in adulthood. PUBMED, Science Direct, Medline, PsychInfo, and PsychArticles databases were searched for eligible studies. Random-effect meta-analyses were used to synthesize effect sizes and to test whether associations of parental divorce with offspring affective disorders differed among three publication periods (i.e., before 1996, 1996-2005, 2006-2015). In total, 29 studies were eligible for the systematic review, and 18 studies were included in the meta-analyses (depression: n=21,581; anxiety: n=2472). There was significant association between parental divorce and offspring depression (OR=1.56; 95%CI [1.31, 1.86]), but not anxiety (OR=1.16; 95%CI [0.98, 1.38]). The effect of parental divorce on offspring depression was not weaker in the reports published in more recent decades. There is limited research in relation to offspring anxiety in adulthood. Parental divorce is associated with an increased risk of adult offspring depression, with no indication of the effect being weaker in recent publications. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasticity of Noddy Parents and Offspring to Sea-Surface Temperature Anomalies

PubMed Central

Devney, Carol A.; Caley, M. Julian; Congdon, Bradley C.

2010-01-01

Behavioral and/or developmental plasticity is crucial for resisting the impacts of environmental stressors. We investigated the plasticity of adult foraging behavior and chick development in an offshore foraging seabird, the black noddy (Anous minutus), during two breeding seasons. The first season had anomalously high sea-surface temperatures and ‘low’ prey availability, while the second was a season of below average sea-surface temperatures and ‘normal’ food availability. During the second season, supplementary feeding of chicks was used to manipulate offspring nutritional status in order to mimic conditions of high prey availability. When sea-surface temperatures were hotter than average, provisioning rates were significantly and negatively impacted at the day-to-day scale. Adults fed chicks during this low-food season smaller meals but at the same rate as chicks in the unfed treatment the following season. Supplementary feeding of chicks during the second season also resulted in delivery of smaller meals by adults, but did not influence feeding rate. Chick begging and parental responses to cessation of food supplementation suggested smaller meals fed to artificially supplemented chicks resulted from a decrease in chick demands associated with satiation, rather than adult behavioral responses to chick condition. During periods of low prey abundance, chicks maintained structural growth while sacrificing body condition and were unable to take advantage of periods of high prey abundance by increasing growth rates. These results suggest that this species expresses limited plasticity in provisioning behavior and offspring development. Consequently, responses to future changes in sea-surface temperature and other environmental variation may be limited. PMID:20686693

Intergenerational Transmission of Overweight and Obesity from Parents to Their Adolescent Offspring - The HUNT Study.

PubMed

Næss, Marit; Holmen, Turid Lingaas; Langaas, Mette; Bjørngaard, Johan Håkon; Kvaløy, Kirsti

2016-01-01

The main aim of this study was to examine weight associations between parents and offspring at two time points: 1995-97 and 2006-08, taking into account body mass index (BMI) and waist circumference. The study included 8425 parent-offspring trios who participated in the population based Health Study of Nord Trøndelag (the HUNT Study), Norway, at either the HUNT2 (1995-97) or the HUNT3 (2006-08) survey. We used linear mixed effects models with siblings clustered within mothers to analyze the associations between 1) parental grouped BMI and offspring BMI z-scores and 2) parental grouped waist circumference and offspring waist circumference z-scores. Adolescent and adult overweight and obesity were higher in 2006-08 than in 1995-97, with the greatest increase observed in waist circumference. Both mother's and father's BMI and waist circumference were strongly associated with corresponding measures in offspring. Compared with both parents being normal weight (BMI <25 kg/m2), having two overweight or obese parents (BMI ≥25 kg/m2) was associated with a higher offspring BMI z-score of 0.76 (95% CI; 0.65, 0.87) and 0.64 (95% CI; 0.48, 0.80) in daughters, and 0.76 (95% CI; 0.65, 0.87) and 0.69 (95% CI; 0.53, 0.80) in sons, in 1995-97 and 2006-08 respectively. Offspring with one parent being overweight/obese had BMI z-scores of approximately half of offspring with two parents categorized as overweight/obese. The results of the waist circumference based analyses did not differ substantially from the BMI based analyses. Parental overweight was strongly positively associated with offspring weight both in 1995-97 and 2006-08 where both parents being overweight/obese gave the largest effect. This seemingly stable association, strongly address the importance of public health initiatives towards preventing obesity in parents of both sexes to decrease further obesity expansion in offspring.

Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice.

PubMed

Bolton, Jessica L; Huff, Nicole C; Smith, Susan H; Mason, S Nicholas; Foster, W Michael; Auten, Richard L; Bilbo, Staci D

2013-09-01

Low socioeconomic status is consistently associated with reduced physical and mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown. We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neurocognitive disorders in adulthood. Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation. Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased proinflammatory interleukin (IL)-1β levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1. These results show that maternal stress during late gestation increases the susceptibility of offspring-particularly males-to the deleterious effects of prenatal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain.

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. Published by Elsevier Inc.

Maternal dietary antigens and the immune response in the offspring of the guinea-pig.

PubMed Central

Telemo, E; Jakobsson, I; Weström, B R; Folkesson, H

1987-01-01

Guinea-pig dams and their litters were raised on either a cow's milk protein-containing diet (MCD) or a milk-free diet (MFD). At 8 weeks of age all litters were challenged i.p. with 50 micrograms milk whey-protein concentrate (V67) and 100 mg A1(OH)3 in saline. The immune response was estimated 2 weeks later as the serum IgG antibody titres against V67, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) using enzyme-linked immunosorbent assay (ELISA) and the tracheal Schulze-Dale response to these antigens. Feeding milk protein antigen to dams from birth and during pregnancy induces antigen-specific hyporesponsiveness (tolerance) in their offspring, despite no direct contact between the offspring and the milk proteins. Tolerance seems to be induced by the antigen itself since withdrawal of the MCD 10 days before delivery reduced tolerance in the offspring. No tolerance was produced in the offspring of dams fed the antigen from 3 months of age (adult). beta-LG appears to be a major antigen in milk whey while alpha-LA is a minor one since there was almost no antibody or tracheal response to alpha-LA in any of the animals tested. The results indicate that maternal antigen experience and antigens present during pregnancy are important for the subsequent immune response to these antigens in offspring. PMID:3653926

Brain metabolic alterations in mice subjected to postnatal traumatic stress and in their offspring.

PubMed

Gapp, Katharina; Corcoba, Alberto; van Steenwyk, Gretchen; Mansuy, Isabelle M; Duarte, João Mn

2017-07-01

Adverse environmental and social conditions early in life have a strong impact on health. They are major risk factors for mental diseases in adulthood and, in some cases, their effects can be transmitted across generations. The consequences of detrimental stress conditions on brain metabolism across generations are not well known. Using high-field (14.1 T) magnetic resonance spectroscopy, we investigated the neurochemical profile of adult male mice exposed to traumatic stress in early postnatal life and of their offspring, and of undisturbed control mice. We found that, relative to controls, early life stress-exposed mice have metabolic alterations consistent with neuronal dysfunction, including reduced concentration of N-acetylaspartate, glutamate and γ-aminobutyrate, in the prefrontal cortex in basal conditions. Their offspring have normal neurochemical profiles in basal conditions. Remarkably, when challenged by an acute cold swim stress, the offspring has attenuated metabolic responses in the prefrontal cortex, hippocampus and striatum. In particular, the expected stress-induced reduction in the concentration of N-acetylaspartate, a putative marker of neuronal health, was prevented in the cortex and hippocampus. These findings suggest that paternal trauma can confer beneficial brain metabolism adaptations to acute stress in the offspring.

The influences of parental divorce and maternal-versus-paternal alcohol abuse on offspring lifetime suicide attempt.

PubMed

Thompson, Ronald G; Alonzo, Dana; Hu, Mei-Chen; Hasin, Deborah S

2017-05-01

Research indicates that parental divorce and parental alcohol abuse independently increase likelihood of offspring lifetime suicide attempt. However, when experienced together, only parental alcohol abuse significantly increased odds of suicide attempt. It is unclear to what extent differences in the effect of maternal versus paternal alcohol use exist on adult offspring lifetime suicide attempt risk. This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime suicide attempt. The sample consisted of participants from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions. The simultaneous effect of childhood or adolescent parental divorce and maternal and paternal history of alcohol problems on offspring lifetime suicide attempt was estimated using a logistic regression model with an interaction term for demographics and parental history of other emotional and behavioural problems. Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime suicide attempt. Experiencing parental divorce and either maternal or paternal alcohol problems nearly doubled the likelihood of suicide attempt. Divorce and history of alcohol problems for both parents tripled the likelihood. Individuals who experienced parental divorce as children or adolescents and who have a parent who abuses alcohol are at elevated risk for lifetime suicide attempt. These problem areas should become a routine part of assessment to better identify those at risk for lifetime suicide attempt and to implement early and targeted intervention to decrease such risk. [Thompson RG Jr,Alonzo D, Hu M-C, Hasin DS. The influences of parental divorce and maternal-versus-paternal alcohol abuse on offspringlifetime suicide attempt. Drug Alcohol Rev 2017;36:408-414]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Parental social networks during childhood and offspring depression in early adulthood: a lifecourse approach.

PubMed

Allchin, Adelyn; Melchior, Maria; Fombonne, Eric; Surkan, Pamela J

2016-07-04

Little is known on how parental social relationships may affect their children's mental health. We sought to examine the relation between parental social relationship characteristics and subsequent offspring depression in young adulthood. We used 2009 Trajectoires Épidémiologiques en Population (TEMPO) study data from 1087 French young adults ages 22 to 35 and parental data from the corresponding Gaz et Eléctricité (GAZEL) study in 1991. Multivariable logistic regression was used to examine parental social networks, quality of parental relationships, and reciprocity of parental social support measured in 1991 in relation to offspring depression in young adulthood measured using the Adult Self Report in 2009. Analyses were stratified by participant sex. In adjusted models, daughters of parents who reported giving more support to others than they received had 1.72 higher odds (95% CI, 1.09-2.70) of depression in young adulthood. Daughters of parents who were unsatisfied with their social relationships had 2.14 (95% CI, 1.22-3.76) higher odds of depression. Among male participants, there was no statistically significant association between parental relationship satisfaction, reciprocity of parental exchanges, and depression. Parental relationships during mid-childhood have long-term associations with offspring depression. Results suggest that enhancing social support for parents may have positive implications for their children's mental health. © 2016 Wiley Periodicals, Inc.

Latent profiles of nonresidential father engagement six years after divorce predict long-term offspring outcomes.

PubMed

Modecki, Kathryn Lynn; Hagan, Melissa J; Sandler, Irwin; Wolchik, Sharlene A

2015-01-01

This study examined profiles of nonresidential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) 6 to 8 years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, 9 years later. Parental divorce occurred during late childhood to early adolescence; indicators of nonresidential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed 9 years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes 9 years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother's remarriage, mother's income, and gender, age, and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems 9 years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long term. Implications of findings for policy and intervention are discussed.

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring.

PubMed

Xue, Baojian; Yin, Haifeng; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Johnson, Alan Kim

2017-04-01

Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II. © 2017 American Heart Association, Inc.

Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

PubMed

Frihauf, Jennifer B; Fekete, Éva M; Nagy, Tim R; Levin, Barry E; Zorrilla, Eric P

2016-12-01

Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. Copyright © 2016 Frihauf et al.

Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers

PubMed Central

Frihauf, Jennifer B.; Fekete, Éva M.; Nagy, Tim R.; Levin, Barry E.

2016-01-01

Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. PMID:27654396

Evidence that a maternal "junk food" diet during pregnancy and lactation can reduce muscle force in offspring.

PubMed

Bayol, Stéphanie A; Macharia, Raymond; Farrington, Samantha J; Simbi, Bigboy H; Stickland, Neil C

2009-02-01

Obesity is a multi-factorial condition generally attributed to an unbalanced diet and lack of exercise. Recent evidence suggests that maternal malnutrition during pregnancy and lactation can also contribute to the development of obesity in offspring. We have developed an animal model in rats to examine the effects of maternal overeating on a westernized "junk food" diet using palatable processed foods rich in fat, sugar and salt designed for human consumption. Using this model, we have shown that such a maternal diet can promote overeating and a greater preference for junk food in offspring at the end of adolescence. The maternal junk food diet also promoted adiposity and muscle atrophy at weaning. Impaired muscle development may permanently affect the function of this tissue including its ability to generate force. The aim of this study is to determine whether a maternal junk food diet can impair muscle force generation in offspring. Twitch and tetanic tensions were measured in offspring fed either chow alone (C) or with a junk food diet (J) during gestation, lactation and/or post-weaning up to the end of adolescence such that three groups of offspring were used, namely the CCC, JJC and JJJ groups. We show that adult offspring from mothers fed the junk food diet in pregnancy and lactation display reduced muscle force (both specific twitch and tetanic tensions) regardless of the post-weaning diet compared with offspring from mothers fed a balanced diet. Maternal malnutrition can influence muscle force production in offspring which may affect an individual's ability to exercise and thereby combat obesity.

Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.

PubMed

Vargas, Vladimir E; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M; Saunders, Debra; Njoku, Charity; Towner, Rheal; Myers, Dean A

2017-01-01

The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15-19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5-8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5-7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4-12 weeks of age fed a CD or HFD. By 14-23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.

Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat

PubMed Central

Vargas, Vladimir E.; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M.; Saunders, Debra; Njoku, Charity; Towner, Rheal

2017-01-01

The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15–19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5–8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5–7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4–12 weeks of age fed a CD or HFD. By 14–23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD. PMID:28957383

Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

PubMed

Canetta, S; Bolkan, S; Padilla-Coreano, N; Song, L J; Sahn, R; Harrison, N L; Gordon, J A; Brown, A; Kellendonk, C

2016-07-01

Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

Maternal immunomodulation of the offspring's immunological system.

PubMed

Campos, Sylvia M N; de Oliveira, Vivian L; Lessa, Leonardo; Vita, Melissa; Conceição, Marcia; Andrade, Luiz Antonio Botelho; Teixeira, Gerlinde Agate Platais Brasil

2014-11-01

The mother's and the offspring's immunological system are closely related thus one can influence the other. This hypothesis drove our aim to study the impact of the mother's immunological status over the immunological response of their offspring. For this, female mice tolerant or allergic to peanuts were exposed or not to a challenge diet containing peanuts during the gestation-lactation period (TEP/AEP; TNEP/ANEP, respectively). After weaning the offspring was submitted to the peanut allergy or peanut tolerization protocol and then challenged with a peanut diet. Our results showed that when the offspring is submitted to the allergy induction protocol, they behave differently depending on their mother's immunological status. Offspring born to TEP mothers produced the lowest antibody titters while those born to AEP mothers produced the highest antibody titters compared to mice born to TNEP and ANEP. On the other hand when the offspring was submitted to the tolerization protocol all groups presented low antibody titers with no significant difference between groups, independent of the mothers immunological status and/or contact with peanuts during the gestation-lactation period. The analysis of the histological profile of the offspring correlates well to the serological response. In other words, offspring born to TEP mothers and submitted to the allergy induction protocol presented a normal histological profile, while the offspring born to AEP mothers produced the worst gut inflammation. These results indicate that mothers, exposed to the antigen (by the oral route) during gestation, actively influence the immune response of their offspring. This work sheds some light on the importance of the immunomodulation induced by dietary antigens during gestation and their influence on the immunological response of their offspring. However, more work is needed to elucidate the molecular and cellular components of this regulatory phenomenon. Copyright © 2014 Elsevier GmbH. All

Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats.

PubMed

Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Piryaei, Abbas; Ghasemi, Asghar

2018-05-01

What is the central question of this study? Does fetal hypothyroidism in rats alter uterine contractions and structure in the adult offspring? What is the main finding and its importance? Our study indicated that maternal hypothyroidism during pregnancy increased gestational length and decreased litter size. In addition, maternal hypothyroidism caused delayed puberty onset, irregular uterine contractions and histological changes in the uterus in the female offspring. This model might contribute to a better understanding of the cellular and molecular mechanisms involved in uterine contractions in fetal hypothyroidism, studies which are not possible in humans, and might help to establish therapeutic methods for these disorders observed in uterine contractions. Thyroid hormones play an essential role in fetal growth. Hypothyroidism impairs reproductive function in both humans and animals. The aim of this study was to assess the effects of fetal hypothyroidism on uterine smooth muscle contraction and structure in the adult offspring. The control group of female Wistar rats consumed tap water, whereas the hypothyroid group received water containing 0.025% of 6-propyl-2-thiouracial throughout gestation from mating until delivery. Isometric contractility and histological changes in uterine tissue were evaluated in the adult female offspring. We tested the effects of carbachol (10 -10 -10 -3  m) and oxytocin (10 -13 -10 -8  m) on uterine smooth muscle contraction in the fetal hypothyroid (FH) and control groups. Compared with control uteri, carbachol induced contractions with lower amplitude in the FH group (area under the curve: 1820.0 ± 250.0 versus 1370.0 ± 125.0 a.u., control versus FH group, respectively, P < 0.001) and frequency (86.4 ± 7.3 versus 37.0 ± 6.1 a.u., P < 0.001). Likewise, after exposure to oxytocin the amplitude (6614.0 ± 492.2 versus 4793.0 ± 735.2 a.u., P < 0.001) and frequency (367.4 ± 32.0 versus 167.0 ± 39.0�

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. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice.

PubMed

Smarr, Benjamin L; Grant, Azure D; Perez, Luz; Zucker, Irving; Kriegsfeld, Lance J

2017-06-12

Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.

Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring

PubMed Central

Desarnaud, Frank; Bader, Heather N.; Makotkine, Iouri; Flory, Janine D.; Bierer, Linda M.; Meaney, Michael J.

2014-01-01

Objective Differential effects of maternal and paternal PTSD have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The current study examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor gene (NR3C1) in peripheral blood mononuclear cells (PBMCs), and its relationship to glucocorticoid receptor sensitivity, in Holocaust offspring. Method Adult offspring with at least one Holocaust survivor parent (n=80), and demographically similar participants without parental Holocaust exposure or PTSD (n=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of glucocorticoid receptor gene exon 1F (GR-1F) promoter methylation and cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical-clustering analysis was used to permit visualization of maternal vs. paternal PTSD effects on clinical variables. Results A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1F promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1F promoter methylation was significantly associated with greater post-dexamethasone cortisol suppression. The clustering analysis confirmed that maternal and paternal PTSD effects were differentially associated with clinical indicators. Conclusions This is the first study to demonstrate alterations of GR-1F promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities. PMID:24832930

Concurrent maternal and pup postnatal tobacco smoke exposure in Wistar rats changes food preference and dopaminergic reward system parameters in the adult male offspring.

PubMed

Pinheiro, C R; Moura, E G; Manhães, A C; Fraga, M C; Claudio-Neto, S; Abreu-Villaça, Y; Oliveira, E; Lisboa, P C

2015-08-20

Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. Nursing Wistar rats and their pups were divided into two groups: tobacco smoke-exposed (S: 4times/day, from the 3rd to the 21th day of lactation), and ambient air-exposed (C). On PN175, both offspring groups were subdivided for a food challenge: S and C that received standard chow (SC) or that chose between high-fat (HFD) and high-sucrose diets (HSDs). Food intake was recorded after 30min and 12h. Offspring were tested in the elevated plus maze and open field on PN178-179; they were euthanized for dopaminergic analysis on PN180. SSD (self-selected diet) animals presented a higher food intake compared to SC ones. S-SSD animals ate more than C-SSD ones at 30min and 12h. Both groups preferred the HFD. However, S-SSD animals consumed relatively more HFD than C-SSD at 30min. No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Maternal choline supplementation in a mouse model of Down syndrome: effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring

PubMed Central

Powers, Brian E.; Kelley, Christy M.; Velazquez, Ramon; Ash, Jessica A.; Strawderman, Myla S.; Alldred, Melissa J.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

2016-01-01

The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer’s disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12–17 months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD. PMID:27840230

Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.

PubMed

Powers, Brian E; Kelley, Christy M; Velazquez, Ramon; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2017-01-06

The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer's disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12-17months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Personality Traits of Centenarians’ Offspring

PubMed Central

Givens, Jane L; Frederick, Maureen; Silverman, Leanne; Anderson, Stacy; Senville, Joanna; Silver, Margery; Sebastiani, Paola; Terry, Dellara F; Costa, Paul T.; Perls, Thomas T.

2010-01-01

OBJECTIVES To determine whether the offspring of centenarians have personality characteristics that are distinct from the general population. DESIGN Case-control. SETTING Nationwide U.S. sample. PARTICIPANTS Unrelated offspring of centenarians (n = 246, mean age 75) were compared with published norms. MEASUREMENTS Using the NEO-Five-Factor Inventory (NEO-FFI) questionnaire, measures of the personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness were obtained. T-scores and percentiles were calculated according to sex and used to interpret the results. RESULTS Male and female offspring of centenarians scored in the low range of published norms for neuroticism and in the high range for extraversion. The women also scored comparatively high in agreeableness. Otherwise, both sexes scored within normal range for conscientiousness and openness, and the men scored within normal range for agreeableness. CONCLUSION Specific personality traits may be important to the relative successful aging demonstrated by the offspring of centenarians. Similarities across four of the five domains between male and female offspring is noteworthy and may relate to their successful aging. Measures of personality are an important phenotype to include in studies that assess genetic and environmental influences of longevity and successful aging. PMID:19392961

Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

PubMed Central

Watkins, Adam J; Wilkins, Adrian; Cunningham, Colm; Perry, V Hugh; Seet, Meei J; Osmond, Clive; Eckert, Judith J; Torrens, Christopher; Cagampang, Felino R A; Cleal, Jane; Gray, William P; Hanson, Mark A; Fleming, Tom P

2008-01-01

Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P < 0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P < 0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P < 0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P < 0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P < 0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome. PMID:18308825

Reproduction of Varroa destructor and offspring mortality in worker and drone brood cells of Africanized honey bees.

PubMed

Calderón, R A; Ureña, S; van Veen, J W

2012-04-01

Varroa destructor is known to be the most serious parasite of Apis mellifera worldwide. In order to reproduce varroa females enter worker or drone brood shortly before the cell is sealed. From March to December 2008, the reproductive rate and offspring mortality (mature and immature stages), focusing on male absence and male mortality of V. destructor, was investigated in naturally infested worker and drone brood of Africanized honey bees (AHB) in Costa Rica. Data were obtained from 388 to 403 single infested worker and drone brood cells, respectively. Mite fertility in worker and drone brood cells was 88.9 and 93.1%, respectively. There was no difference between the groups (X(2) = 3.6, P = 0.06). However, one of the most significant differences in mite reproduction was the higher percentage of mites producing viable offspring in drone cells (64.8%) compared to worker cells (37.6%) (X(2) = 57.2, P < 0.05). A greater proportion of mites in worker brood cells produced non-viable female offspring. Mite offspring mortality in both worker and drone cells was high in the protonymph stage (mobile and immobile). A significant finding was the high rate of male mortality. The worker and drone brood revealed that 23.9 and 6.9%, respectively, of the adult male offspring was found dead. If the absence (missing) of the male and adult male mortality are taken together the percentage of cells increased to 40.0 and 21.3% in worker and drone cells, respectively (X(2) = 28.8, P < 0.05). The absence of the male or male mortality in a considerable number of worker cells naturally infested with varroa is the major factor in our study which reduces the production of viable daughters in AHB colonies in Costa Rica.

Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring.

PubMed

McCormack, Ursula M; Curião, Tânia; Wilkinson, Toby; Metzler-Zebeli, Barbara U; Reyer, Henry; Ryan, Tomas; Calderon-Diaz, Julia A; Crispie, Fiona; Cotter, Paul D; Creevey, Christopher J; Gardiner, Gillian E; Lawlor, Peadar G

2018-01-01

Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring's intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia , respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed

Maternal epilepsy and offsprings' adult intelligence: a population-based study from Norway.

PubMed

Øyen, Nina; Vollset, Stein E; Eide, Martha G; Bjerkedal, Tor; Skjaerven, Rolv

2007-09-01

We examined if children of mothers with epilepsy had normal intelligence, speculating that either epilepsy or its therapy might affect this parameter. In a population-based cohort study in Norway, information on maternal epilepsy reported to the Medical Birth Registry of Norway, 1967-1979 was linked to information on 18-19-year-old men's intellectual ability and anthropometric measures ascertained by the Norwegian Conscripts Service, 1984-1999. The standardized intelligence test (IQ score) was reported as single-digit standard scores with values from 1 to 9. No individual information on antiepileptic drug therapy was available. Mean IQ score was lower in 1,207 conscripts whose mothers had epilepsy reported on the birth notification form, as compared with 316,554 conscripts of mothers without epilepsy; 4.8 (standard deviation 1.8) versus 5.2(1.8), p < 0.001, respectively. This difference remained after adjustment for maternal education, maternal age, birth order, marital status, year of birth, and weight and length at birth. When comparing men with and without reported maternal epilepsy, the odds ratio of having an IQ score < or = 3 was 1.6 (95% confidence interval: 1.4-1.8), which was unaffected by adjustment for confounding factors. Mean height among conscripts of mothers with and without epilepsy measured 178.6 and 179.9 cm, respectively, a difference of 1.3 cm (p < 0.001). We observed that almost 20 years after birth, maternal epilepsy was associated with reduced IQ score and also shorter adult height in male offspring. We do not know whether these findings will persist when epilepsy is better treated with the newer and safer generation of antiepileptic drugs.

Latent profiles of non-residential father engagement six years after divorce predict long term offspring outcomes

PubMed Central

Modecki, Kathryn Lynn; Hagan, Melissa; Sandler, Irwin; Wolchik, Sharlene

2014-01-01

This study examined profiles of non-residential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) six to eight years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, nine years later. Parental divorce occurred during late childhood to early adolescence; indicators of non-residential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed nine years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes nine years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother’s remarriage, mother’s income, and gender, age and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems nine years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long-term. Implications of findings for policy and intervention are discussed. PMID:24484456

Dietary Protein Intake Is Protective Against Loss of Grip Strength Among Older Adults in the Framingham Offspring Cohort

PubMed Central

McLean, Robert R.; Mangano, Kelsey M.; Hannan, Marian T.; Kiel, Douglas P.

2016-01-01

Abstract Background: Age-related decline in muscle strength is an important public health issue for older adults. Dietary protein has been associated with maintenance of muscle mass, yet its relation to muscle strength remains unclear. Methods: We determined the association of dietary protein (total, animal, and plant) intake, measured by food frequency questionnaire, with change in grip strength over 6 years in 1,746 men and women from the Framingham Offspring cohort. Results: Mean age at baseline was 58.7 years (range: 29–85), and mean total, animal, and plant protein intakes were 79, 57, and 22g/d, respectively. Adjusted baseline mean grip strength did not differ across quartiles of energy-adjusted total, animal or protein intake. Greater protein intake, regardless of source, was associated with less decrease in grip strength (all p for trend ≤.05): participants in the lowest quartiles lost 0.17% to 0.27% per year while those in the highest quartiles gained 0.52% to 0.60% per year. In analyses stratified by age, participants aged 60 years or older ( n = 646) had similar linear trends on loss of grip strength for total and animal (all p for trend <.03) but not plant protein, while the trends in participants younger than 60 years ( n = 896) were not statistically significant. Conclusions: Higher dietary intakes of total and animal protein were protective against loss of grip strength in community-dwelling adults aged 60 years and older. Increasing intake of protein from these sources may help maintain muscle strength and support prevention of mobility impairment in older adults. PMID:26525088

The Proteome of Native Adult Müller Glial Cells From Murine Retina*

PubMed Central

Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca

2016-01-01

To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

Adult children's education and changes to parents' physical health in Mexico.

PubMed

Yahirun, Jenjira J; Sheehan, Connor M; Hayward, Mark D

2017-05-01

The well-being of older adults is frequently tied to support from their adult children. Here, we assess whether the education of adult offspring is associated with changes to older parents' short- and long-term health in Mexico, a rapidly aging context with historically limited institutional support for the elderly. Educational expansion over the past half century, however, provides older adults with greater resources to rely on via the education of their children. Using longitudinal data from the Mexican Health and Aging Study (2001-2012), we find that offspring education is not associated with short-term changes in parents' physical functioning, but is associated with increased parental longevity, net of children's financial status and transfers. In addition, we find that mothers' longevity is more sensitive to offspring education than fathers. Our findings add to a growing body of literature that urges policy-makers to consider the multi-generational advantages of expanding educational opportunities in Mexico. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parental Educational Attainment and Offspring Subjective Well-being and Self-Beliefs in Older Adulthood.

PubMed

Sutin, Angelina R; Stephan, Yannick; Terracciano, Antonio

2018-07-01

This research examines whether parental educational attainment and subjective childhood socioeconomic status (SES) is associated with adult offspring well-being and self-beliefs (broadly defined). Participants from the Health and Retirement Study were included if they completed the leave-behind questionnaire in 2006 or 2008 ( N =10,827; M age =68.38; SD =9.81; range=50-101). Participants reported on their own and both parents educational attainment, subjective childhood financial situation, and financial difficulties in childhood at study entry and on well-being in 2006/2008. Linear regression was used to examine the association between offspring education, parental education, childhood SES and three aspects of well-being and self-beliefs: positive affect (e.g., positive emotions, optimism), negative affect (e.g., loneliness, hostility), and cognitive evaluation (e.g., life satisfaction). Participants with more education reported higher well-being (median β=.12). Parental educational attainment, subjective childhood SES, and a significant financial event during childhood were associated with more positive affect, less negative affect, and higher life satisfaction (median β=.05); these associations held controlling for offspring education. The educational and financial environment of childhood may hamper well-being into older adulthood; the offspring's own experiences and achievements do not completely attenuate the association with these aspects of the childhood environment.

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…

Parent, Sibling and Peer Associations with Subtypes of Psychiatric and Substance Use Disorder Comorbidity in Offspring

PubMed Central

McCutcheon, Vivia V.; Scherrer, Jeffrey F.; Grant, Julia D.; Xian, Hong; Haber, Jon Randolph; Jacob, Theodore; Bucholz, Kathleen K

2012-01-01

BACKGROUND Parental substance use disorder (SUD) is associated with a range of negative offspring outcomes and psychopathology, but the clustering of these outcomes into subtypes has seldom been examined, nor have the familial and environmental contexts of these subtypes been reported. The present study examines the clustering of offspring lifetime substance use and psychiatric disorders into subtypes and characterizes them in terms of familial and non-familial influences using an offspring-of-twins design. METHOD Telephone-administered diagnostic interviews were used to collect data on psychiatric disorders and SUD from 488 twin fathers, 420 biological mothers and 831 offspring. Latent class analysis (LCA) was used to derive subtypes of lifetime comorbidity in offspring. Familial risk and environmental variables associated with each subtype (i.e. parenting, childhood physical or sexual abuse, perceived sibling and peer substance use) were identified using multinomial logistic regression. RESULTS Four classes identified by LCA were characterized as 1) unaffected, 2) alcohol abuse/dependence, 3) alcohol abuse/dependence comorbid with anxiety and depression, and 4) alcohol, cannabis abuse/dependence and nicotine dependence comorbid with conduct disorder. Inconsistent parenting, childhood physical/sexual abuse, and perceived sibling and peer substance use were significantly associated with profiles of offspring comorbidity after adjusting for familial vulnerability. Some associations were specific (i.e. perceived peer alcohol use to the AUD class), while others were general (peer smoking to all 3 comorbidity classes). CONCLUSIONS We observed distinct subtypes of psychiatric and SUD comorbidity in adolescents and young adults. Subtypes of offspring psychopathology have varied associations with parental psychopathology, family environment, and sibling and peer behaviors. PMID:22921146

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...

Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

PubMed Central

López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

2016-01-01

Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

Psychosocial functioning in offspring of parents with bipolar disorder.

PubMed

Bella, Tolulope; Goldstein, Tina; Axelson, David; Obreja, Mihaela; Monk, Kelly; Hickey, Mary Beth; Goldstein, Benjamin; Brent, David; Diler, Rasim Somer; Kupfer, David; Sakolsky, Dara; Birmaher, Boris

2011-09-01

Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Children's Global Assessment Scale (CGAS). Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the child's Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the child's own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the child's psychopathology may help reduce the risk for long-term functional impairment in offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

PubMed Central

Aldhous, Marian C.; Reynolds, Rebecca M.; Campbell, Archie; Linksted, Pamela; Lindsay, Robert S.; Smith, Blair H.; Seckl, Jonathan R.; Porteous, David J.; Norman, Jane E.

2015-01-01

Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects’ own diabetes medical records. From F0-parents, we identified F1-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F1-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03–3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13–1.30) and age (OR = 1.03, CI 1.01–1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09–1.29) and percent body-fat (OR = 1.12, CI 1.05–1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved. PMID:26308734

Psychological stress has a higher rate of developing addictive behaviors compared to physical stress in rat offspring

PubMed Central

Nazeri, Masoud; Ebrahimi, Arezoo; Aghaei, Iraj; Ghotbi Ravandi, Samaneh; Shabani, Mohammad

2017-01-01

Prenatal stress could have great influence on development of offspring and might alter cognitive function and other physiological processes of children. The current study was conducted to study the effect of physical or psychological prenatal stress on addictive and anxiety-like behavior of male and female offspring during their adolescence period (postnatal day (PND) 40). Adult female rats were exposed to physical (swimming) or psychological (observing another female rat swimming) stress from day six of gestation for 10 days. Male and female offspring were assayed for anxiety-like behavior, motor and balance function and morphine conditioned place preference using the open field, elevated plus maze (EPM), rotarod and wire grip assay and conditioned place preference. Offspring in both physical and psychological prenatal stress groups demonstrated significant increase in anxiety-like behavior in EPM paradigm, but no alterations were observed in motor and balance function of animals. Offspring in the psychological prenatal stress group had an increased preference for morphine in comparison to control and physical prenatal stress groups. Results of the current study demonstrated that animals exposed to psychological stress during fetal development are at a higher risk of developing addictive behaviors. Further research might elucidate the exact mechanisms involved to provide better preventive and therapeutic interventions. PMID:28900372

Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

PubMed

Smith, B L; Reyes, T M

2017-10-01

Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

Elliott, Kyle Hamish; Chivers, Lorraine S; Bessey, Lauren; Gaston, Anthony J; Hatch, Scott A; Kato, Akiko; Osborne, Orla; Ropert-Coudert, Yan; Speakman, John R; Hare, James F

2014-01-01

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. 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. 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.

Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort

USDA-ARS?s Scientific Manuscript database

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...

Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring.

PubMed

Yehuda, Rachel; Daskalakis, Nikolaos P; Lehrner, Amy; Desarnaud, Frank; Bader, Heather N; Makotkine, Iouri; Flory, Janine D; Bierer, Linda M; Meaney, Michael J

2014-08-01

Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor (GR-1F) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring. Adult offspring with at least one Holocaust survivor parent (N=80) and demographically similar participants without parental Holocaust exposure or parental PTSD (N=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of GR-1F promoter methylation and of cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical clustering analysis was used to permit visualization of maternal compared with paternal PTSD effects on clinical variables and GR-1F promoter methylation. A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1F promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1F promoter methylation was significantly associated with greater postdexamethasone cortisol suppression. The clustering analysis revealed that maternal and paternal PTSD effects were differentially associated with clinical indicators and GR-1F promoter methylation. This is the first study to demonstrate alterations of GR-1F promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities.

Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring.

PubMed

Walton, Sarah L; Singh, Reetu R; Tan, Tiffany; Paravicini, Tamara M; Moritz, Karen M

2016-03-01

Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Sex roles, parental care and offspring growth in two contrasting coucal species.

PubMed

Goymann, Wolfgang; Safari, Ignas; Muck, Christina; Schwabl, Ingrid

2016-10-01

The decision to provide parental care is often associated with trade-offs, because resources allocated to parental care typically cannot be invested in self-maintenance or mating. In most animals, females provide more parental care than males, but the reason for this pattern is still debated in evolutionary ecology. To better understand sex differences in parental care and its consequences, we need to study closely related species where the sexes differ in offspring care. We investigated parental care in relation to offspring growth in two closely related coucal species that fundamentally differ in sex roles and parental care, but live in the same food-rich habitat with a benign climate and have a similar breeding phenology. Incubation patterns differed and uniparental male black coucals fed their offspring two times more often than female and male white-browed coucals combined. Also, white-browed coucals had more 'off-times' than male black coucals, during which they perched and preened. However, these differences in parental care were not reflected in offspring growth, probably because white-browed coucals fed their nestlings a larger proportion of frogs than insects. A food-rich habitat with a benign climate may be a necessary, but-perhaps unsurprisingly-is not a sufficient factor for the evolution of uniparental care. In combination with previous results (Goymann et al . 2015 J. Evol. Biol . 28 , 1335-1353 (doi:10.1111/jeb.12657)), these data suggest that white-browed coucals may cooperate in parental care, because they lack opportunities to become polygamous rather than because both parents were needed to successfully raise all offspring. Our case study supports recent theory suggesting that permissive environmental conditions in combination with a particular life history may induce sexual selection in females. A positive feedback loop among sexual selection, body size and adult sex-ratio may then stabilize reversed sex roles in competition and parental care.

Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue.

PubMed

Lecoutre, Simon; Deracinois, Barbara; Laborie, Christine; Eberlé, Delphine; Guinez, Céline; Panchenko, Polina E; Lesage, Jean; Vieau, Didier; Junien, Claudine; Gabory, Anne; Breton, Christophe

2016-07-01

According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner. © 2016 Society for Endocrinology.

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.

Problem partners and parenting: exploring linkages with maternal insecure attachment style and adolescent offspring internalizing disorder.

PubMed

Bifulco, Antonia; Moran, Patricia; Jacobs, Catherine; Bunn, Amanda

2009-01-01

An intergenerational study examined mothers' insecure attachment style using the Attachment Style Interview (ASI; Bifulco et al., 2002a) in relation to her history of partner relationships, her parenting competence, and depression or anxiety disorder in her offspring. The sample comprised 146 high-risk, mother-adolescent offspring pairs in London, who were recruited on the basis of the mothers' psychosocial vulnerability for depression. Retrospective, biographical, and clinical interviews were undertaken independently with mother and offspring. A path model was developed, which showed that mothers' insecure attachment style had no direct link to either recalled child neglect/abuse or currently assessed disorder in their adolescent and young adult offspring. The connections appeared to be indirect, through the quality of relationships in the family system: mothers' insecure attachment and their partners' problem behavior accounted for variance in mothers' incompetent parenting as rated by interviewers. These variables predicted her neglect/abuse of the child, which was the only variable directly associated with internalizing disorder in her offspring. Mother's lifetime depression did not add to the model. It is argued that an ecological approach (emphasizing social adversity and different role domains) and a lifespan approach (emphasizing a history of adverse relationships a different life stages) is important in understanding the mechanisms by which parental insecure attachment style influences transmission of risk to the next generation.

Adult children’s education and changes to parents’ physical health in Mexico

PubMed Central

Yahirun, Jenjira J.; Sheehan, Connor M.; Hayward, Mark D.

2017-01-01

The well-being of older adults is frequently tied to support from their adult children. Here, we assess whether the education of adult offspring is associated with changes to older parents’ short- and long-term health in Mexico, a rapidly aging context with historically limited institutional support for the elderly. Educational expansion over the past half century, however, provides older adults with greater resources to rely on via the education of their children. Using longitudinal data from the Mexican Health and Aging Study (2001–2012), we find that offspring education is not associated with short-term changes in parents’ physical functioning, but is associated with increased parental longevity, net of children’s financial status and transfers. In addition, we find that mothers’ longevity is more sensitive to offspring education than fathers. Our findings add to a growing body of literature that urges policy-makers to consider the multi-generational advantages of expanding educational opportunities in Mexico. PMID:28384483

The influence of maternal condition on offspring performance in sockeye salmon Oncorhynchus nerka.

PubMed

Tierney, K B; Patterson, D A; Kennedy, C J

2009-10-01

Eggs were taken from adult sockeye salmon Oncorhynchus nerka that had reached their journey's end in spawn-ready and moribund condition, and fertilized by healthy males. Egg number, size, hatching success and offspring growth did not differ with maternal condition, which suggests the absence of any persisting physiological maternal effects. Differences were noted in the swimming behaviour and physiology of the offspring at parr stage. In a 30 min schooling test conducted using groups of five in a flume, parr from moribund females were more likely to fatigue, were not as tightly schooled, and had a diminished startle response, both in the per cent responding and the burst distance. In individual, confined swimming tests conducted within a tube, post-exercise plasma lactate concentration, which is an indicator of white muscle use, was greater for parr from moribund adult females. The moribund females also had elevated lactate following exercise (their migration), which suggests heritable differences may exist in muscle use. This study shows that juvenile O. nerka artificially propagated from females exhausted by their return migration can exhibit swimming performance differences, indicating that maternal condition may need to be considered in breeding programmes.

Chronic Sleep Restriction during Pregnancy - Repercussion on Cardiovascular and Renal Functioning of Male Offspring

PubMed Central

Lima, Ingrid L. B.; Rodrigues, Aline F. A. C.; Bergamaschi, Cássia T.; Campos, Ruy R.; Hirata, Aparecida E.; Tufik, Sergio; Xylaras, Beatriz D. P.; Visniauskas, Bruna; Chagas, Jair R.; Gomes, Guiomar N.

2014-01-01

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi – tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127±2.6 (19); OCSR: 144±2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: −2.6±0.15 (9); OCRS: −1.6±0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4±15 (18); OSR: 60.2±3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4±0.2 (10); OCSR: 7.4±0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring. PMID:25405471

Chronic sleep restriction during pregnancy--repercussion on cardiovascular and renal functioning of male offspring.

PubMed

Lima, Ingrid L B; Rodrigues, Aline F A C; Bergamaschi, Cássia T; Campos, Ruy R; Hirata, Aparecida E; Tufik, Sergio; Xylaras, Beatriz D P; Visniauskas, Bruna; Chagas, Jair R; Gomes, Guiomar N

2014-01-01

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi - tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127 ± 2.6 (19); OCSR: 144 ± 2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: -2.6 ± 0.15 (9); OCRS: -1.6 ± 0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4 ± 15 (18); OSR: 60.2 ± 3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4 ± 0.2 (10); OCSR: 7.4 ± 0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring.

The psychological, social, and behavioural impact of a parent's cancer on adolescent and young adult offspring aged 10-24 at time of diagnosis: A systematic review.

PubMed

Morris, Julia; Turnbull, Deborah; Preen, David; Zajac, Ian; Martini, Angelita

2018-06-01

This study reviewed the literature regarding the psychological, social, and behavioural impact of parental cancer on offspring aged 10-24 years, at the time of the parent's first diagnosis. A systematic literature review was conducted following 2015 PRISMA guidelines. Seven studies met inclusion criteria. Offspring were impacted by their parent's cancer and experienced psychological and behavioural problems. Daughters and offspring who experienced more problems at their parent's diagnosis appeared to be most impacted. Offspring refrained from communicating their disease-related concerns, but expected their parents to communicate openly. Turning to oneself and peer-support were coping strategies used by offspring. The majority of offspring were significantly impacted by their parent's cancer. The paucity of literature focusing on offspring aged 10-24 years at the time of their parent's incident cancer diagnosis indicates that research has overlooked offspring age at their parent's cancer onset as a factor that may influence their future outcomes. Copyright © 2018. Published by Elsevier Ltd.

The exposure to Trichilia catigua (catuaba) crude extract impairs fertility of adult female rats but does not cause reproductive damage to male offspring.

PubMed

Dos Santos, Alice Hartmann; Ramos, Aline Camargo; Silveira, Kennia Moura; Kiss, Ana Carolina Inhasz; Longhini, Renata; Diniz, Andréa; de Mello, João Carlos Palazzo; Gerardin, Daniela Cristina Ceccatto

2015-05-26

Trichilia catigua is broadly used in folk medicine due to its mental and physical tonic activities and stimulant effects. In animal models, its antidepressant-like effects have been associated with the dopaminergic (DA) system modulation, which has an important role on maternal behavior and male offspring reproductive development. Since little is known about the adverse effects of the exposure to T. catigua crude extract (CAT) in rats, specially regarding maternal homeostasis and offspring development, the aim of the present study was to evaluate whether CAT exposure may influence maternal toxicity parameters and behavior or disrupt male offspring physical and reproductive development. Dams were treated daily (by gavage) with 400mg/kg of CAT or vehicle (control=CTR) throughout pregnancy and lactation. Fertility and maternal behavior tests were conducted in dams. Male offspring reproductive and behavioral parameters were analyzed. Dams exposed to CAT showed increased pre- and post-implantation losses rates when compared to CTR group. No significant changes regarding maternal behavior or male offspring parameters were observed. In conclusion, maternal exposure to CAT interfered with implantation during the initial phases of pregnancy but did not induce changes on maternal behavior or male offspring reproductive and behavioral parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effect of offspring on depressive disorder among old adults: Evidence from the Korean Longitudinal Study of Aging from 2006 to 2012.

PubMed

Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Choi, Young; Park, Eun-Cheol

2015-01-01

To investigate whether having an offspring protects against or increases the risk of depressive disorders. Data from the Korean Longitudinal Study of Aging (KLoSA) from 2006 and 2012 was assessed using longitudinal data analysis. We have included 10,149 research subjects at baseline and estimated the prevalence of depressive disorders for those with children. The number of offspring was from zero to five or more, and the composition of offspring is from zero boys and zero girls to two or more boys and two or more girls. For parents with zero offspring, the estimate for depressive disorder was 0.464 higher (SE: 0.123, p-value: 0.000, OR: 1.389; 95% CI: 1.176-1.640) and for parents with five or more offspring, the estimate for depressive disorder was 0.1 higher (SE: 0.104, p-value: 0.013, OR: 1.315; 95% CI: 1.150-1.504) compared to parents with two offspring. For parents with zero boys and zero girls, the estimate for depressive disorder was 0.599 higher (SE: 4.750, p-value: <0.0001, OR: 1.539; 95% CI: 1.298-1.825), and for parents with two or more boys and two or more girls, the estimate for depressive disorder was 1.328 higher (SE: 3.820, p-value: 0.000, OR: 1.328; 95% CI: 1.189-1.482) compared to parents with one boy and one girl. Our results indicate that there is a large effect of offspring on the prevalence of depressive disorder, with significant positive effects for mothers. Fathers are at lower risk for depressive disorder than mothers, and the graph was U-shaped. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Quantitative-MFG Test: A Linear Mixed Effect Model to Detect Maternal-Offspring Gene Interactions.

PubMed

Clark, Michelle M; Blangero, John; Dyer, Thomas D; Sobel, Eric M; Sinsheimer, Janet S

2016-01-01

Maternal-offspring gene interactions, aka maternal-fetal genotype (MFG) incompatibilities, are neglected in complex diseases and quantitative trait studies. They are implicated in birth to adult onset diseases but there are limited ways to investigate their influence on quantitative traits. We present the quantitative-MFG (QMFG) test, a linear mixed model where maternal and offspring genotypes are fixed effects and residual correlations between family members are random effects. The QMFG handles families of any size, common or general scenarios of MFG incompatibility, and additional covariates. We develop likelihood ratio tests (LRTs) and rapid score tests and show they provide correct inference. In addition, the LRT's alternative model provides unbiased parameter estimates. We show that testing the association of SNPs by fitting a standard model, which only considers the offspring genotypes, has very low power or can lead to incorrect conclusions. We also show that offspring genetic effects are missed if the MFG modeling assumptions are too restrictive. With genome-wide association study data from the San Antonio Family Heart Study, we demonstrate that the QMFG score test is an effective and rapid screening tool. The QMFG test therefore has important potential to identify pathways of complex diseases for which the genetic etiology remains to be discovered. © 2015 John Wiley & Sons Ltd/University College London.

Effect of rat parental morphine exposure on passive avoidance memory and morphine conditioned place preference in male offspring.

PubMed

Akbarabadi, Ardeshir; Niknamfar, Saba; Vousooghi, Nasim; Sadat-Shirazi, Mitra-Sadat; Toolee, Heidar; Zarrindast, Mohammad-Reza

2018-02-01

Drug addiction is a chronic disorder resulted from complex interaction of genetic, environmental, and developmental factors. Epigenetic mechanisms play an important role in the development and maintenance of addiction and also memory formation in the brain. We have examined passive avoidance memory and morphine conditioned place preference (CPP) in the offspring of male and/or female rats with a history of adulthood morphine consumption. Adult male and female animals received chronic oral morphine for 21days and then were maintained drug free for 10days. After that, they were let to mate with either an abstinent or control rat. Male offspring's memory was evaluated by step through test. Besides, rewarding effects of morphine were checked with CCP paradigm. Offspring of abstinent animals showed significant memory impairment compared to the control group which was more prominent in the offspring of abstinent females. Conditioning results showed that administration of a high dose of morphine (10mg/kg) that could significantly induce CPP in control rats, was not able to induce similar results in the offspring of morphine abstinent parents; and CPP was much more prominent when it was induced in the offspring of morphine exposed females compared to the progeny of morphine exposed males. It is concluded that parental morphine consumption in adulthood even before mating has destructive effects on memory state of the male offspring and also leads to tolerance to the rewarding effects of morphine. These effects are greater when the morphine consumer parent is the female one. Copyright © 2017 Elsevier Inc. All rights reserved.

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

The Social Environment and Neurogenesis in the Adult Mammalian Brain

PubMed Central

Lieberwirth, Claudia; Wang, Zuoxin

2012-01-01

Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

Developmental fluoxetine and prenatal stress effects on serotonin, dopamine, and synaptophysin density in the PFC and hippocampus of offspring at weaning.

PubMed

Gemmel, Mary; Rayen, Ine; Lotus, Tiffany; van Donkelaar, Eva; Steinbusch, Harry W; De Lacalle, Sonsoles; Kokras, Nikolaos; Dalla, Christina; Pawluski, Jodi L

2016-04-01

Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning. © 2015 Wiley Periodicals, Inc.

The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.

PubMed

Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia; Najman, Jake

2014-01-01

Cross-sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20 years, and completed a questionnaire about their own depressive symptoms 2 to 5 years later. Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Poor physical health in early childhood and its effects on young adults' social functioning and levels of health related stress is one important pathway by which maternal depression has long-term consequences for offspring mental health. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring

PubMed Central

2018-01-01

ABSTRACT Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring’s intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia, respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from

Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

PubMed

Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A; Dalmeijer, Gerdien W; Evelein, Annemieke M V; Fauser, Bart C J M; de Jager, Wilco

2016-01-01

To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Cross-sectional comparison of serum biomarkers. University Medical Center Utrecht. Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30). Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing. In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory

Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study

PubMed Central

Daan, Nadine M. P.; Koster, Maria P. H.; de Wilde, Marlieke A.; Dalmeijer, Gerdien W.; Evelein, Annemieke M. V.; Fauser, Bart C. J. M.; de Jager, Wilco

2016-01-01

Objective To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Design Cross-sectional comparison of serum biomarkers. Setting University Medical Center Utrecht. Patients Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6–8 years), and a paedriatic reference population (n = 30). Main Outcome Measure(s) Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). Results The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing. Conclusion In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison.

PubMed

Mesman, Esther; Birmaher, Boris B; Goldstein, Benjamin I; Goldstein, Tina; Derks, Eske M; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J; Reichart, Catrien G; Wals, Marjolein; Verhulst, Frank C; Nolen, Willem A; Hillegers, Manon H J

2016-11-15

Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. Preliminary measure of inter-site reliability. We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. Copyright © 2016 Elsevier B.V. All rights reserved.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison✩

PubMed Central

Mesman, Esther; Birmaher, Boris B.; Goldstein, Benjamin I.; Goldstein, Tina; Derks, Eske M.; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J.; Reichart, Catrien G.; Wals, Marjolein; Verhulst, Frank C.; Nolen, Willem A.; Hillegers, Manon H.J.

2017-01-01

Objective Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. Methods We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10–18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Results Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. Limitations Preliminary measure of inter-site reliability. Conclusions We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. PMID:27423424

Maternal exposure to benzo[b]fluoranthene disturbs reproductive performance in male offspring mice.

PubMed

Kim, Ahyoung; Park, Mira; Yoon, Tae Ki; Lee, Woo Sik; Ko, Jeong-Jae; Lee, Kangseok; Bae, Jeehyeon

2011-05-30

Polycyclic aromatic hydrocarbons (PAHs) are a large family of environmentally prevalent toxic compounds generated from the combustion of organic materials and diesel exhaust. Humans and wild animals are exposed to PAHs mostly through dietary intake of contaminated food. Benzo[b]fluoranthene (B[b]F) is a common constituent of PAH complexes present in diverse types of food. B[b]F has been found in human milk, raising the demand for the need for risk assessment of offspring after maternal exposure to B[b]F. In the present study, pregnant mice were orally exposed to low doses (2-2000μg/kg body weight) of B[b]F during gestational and lactational periods, and their male offspring were assessed. Maternal B[b]F exposure disturbed normal sperm function in F1 offspring. To understand the molecular and cellular mechanisms by which the perinatal exposure to B[b]F decreased sperm quality, the testes of young adult F1 mice were examined for changes in expression of steroidogenesis-related and testicular apoptosis mediators and found that aryl hydrocarbon receptor, estrogen receptor α, and a set of proapoptotic proteins including Bax, Noxa, Bad, and Bim were significantly upregulated. Therefore, the current transgenerational animal study implies that consumption of PAH-contaminated diets by mothers may possibly influence their offspring to cause dysfunctional male reproductive function in humans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Good Daphnia parents do not control the offspring microbiome.

PubMed

Douglas, Angela E

2018-03-01

In Focus: Mushegian, A. A., Walser, J. -C., Sullam, K. E., & Ebert, D. (2018). The microbiota of diapause: How host-microbe associations are formed after dormancy in an aquatic crustacean. Journal of Animal Ecology, 87, 400-413. https://doi.org/10.1111/1365-2656.12709. All animals are colonized by micro-organisms, most of which are benign or beneficial. Where do these micro-organisms come from? Theory predicts that micro-organisms which are transmitted vertically from parent to offspring are especially likely to be beneficial to the host, while horizontally acquired micro-organisms are opportunistic and more variable in their impact on host performance. In this issue, Mushegian et al. () investigate the source of bacteria that are required for the growth and development of Daphnia water fleas to reproductive adults. They find that, although vertically transmitted bacteria can occur in the capsule enclosing the Daphnia eggs, the micro-organisms that promote Daphnia performance are associated with the external surface of the capsule and are of likely environmental origin. This mode of transmission may be adaptive for Daphnia because, linked to the longevity and capacity for long-distance dispersal of these eggs, the environmental circumstances encountered by parent and offspring may be different; with the implication, the parental micro-organisms may not be optimal for the offspring. This study demonstrates that, although some animals require symbioses with specific coevolved, vertically transmitted microbial symbionts, other animals have evolved dependence on taxonomically variable micro-organisms of environmental origin. © 2018 The Author. Journal of Animal Ecology © 2018 British Ecological Society.

Low offspring survival in mountain pine beetle infesting the resistant Great Basin bristlecone pine supports the preference-performance hypothesis.

PubMed

Eidson, Erika L; Mock, Karen E; Bentz, Barbara J

2018-01-01

The preference-performance hypothesis states that ovipositing phytophagous insects will select host plants that are well-suited for their offspring and avoid host plants that do not support offspring performance (survival, development and fitness). The mountain pine beetle (Dendroctonus ponderosae), a native insect herbivore in western North America, can successfully attack and reproduce in most species of Pinus throughout its native range. However, mountain pine beetles avoid attacking Great Basin bristlecone pine (Pinus longaeva), despite recent climate-driven increases in mountain pine beetle populations at the high elevations where Great Basin bristlecone pine grows. Low preference for a potential host plant species may not persist if the plant supports favorable insect offspring performance, and Great Basin bristlecone pine suitability for mountain pine beetle offspring performance is unclear. We infested cut bolts of Great Basin bristlecone pine and two susceptible host tree species, limber (P. flexilis) and lodgepole (P. contorta) pines with adult mountain pine beetles and compared offspring performance. To investigate the potential for variation in offspring performance among mountain pine beetles from different areas, we tested beetles from geographically-separated populations within and outside the current range of Great Basin bristlecone pine. Although mountain pine beetles constructed galleries and laid viable eggs in all three tree species, extremely few offspring emerged from Great Basin bristlecone pine, regardless of the beetle population. Our observed low offspring performance in Great Basin bristlecone pine corresponds with previously documented low mountain pine beetle attack preference. A low preference-low performance relationship suggests that Great Basin bristlecone pine resistance to mountain pine beetle is likely to be retained through climate-driven high-elevation mountain pine beetle outbreaks.