Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring.

PubMed

Zhao, Mei; Yuan, Li; Yuan, Man-Man; Huang, Li-Li; Su, Chang; Chen, Yuan-Hua; Yang, Yu-Ying; Hu, Yan; Xu, De-Xiang

2018-04-01

An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 μg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERβ expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to clarify the pathogenesis of maternal infection-related diabetes in male offspring. Copyright © 2018 Elsevier B.V. All rights reserved.

The early origins of obesity and insulin resistance: timing, programming and mechanisms.

PubMed

Nicholas, L M; Morrison, J L; Rattanatray, L; Zhang, S; Ozanne, S E; McMillen, I C

2016-02-01

Maternal obesity is associated with an increased risk of developing gestational diabetes mellitus and it also results in an increased risk of giving birth to a large baby with increased fat mass. Furthermore, it is also contributes to an increased risk of obesity and insulin resistance in the offspring in childhood, adolescence and adult life. It has been proposed that exposure to maternal obesity may therefore result in an 'intergenerational cycle' of obesity and insulin resistance. There is significant interest in whether exposure to maternal obesity around the time of conception alone contributes directly to poor metabolic outcomes in the offspring and whether dieting in the obese mother before pregnancy or around the time of conception has metabolic benefits for the offspring. This review focusses on experimental and clinical studies that have investigated the specific impact of exposure to maternal obesity during the periconceptional period alone or extending beyond conception on adipogenesis, lipogenesis and on insulin signalling pathways in the fat, liver and muscle of the offspring. Findings from these studies highlight the need for a better evidence base for the development of dietary interventions in obese women before pregnancy and around the time of conception to maximize the metabolic benefits and minimize the metabolic costs for the next generation.

Mother knows best, even when stressed? Effects of maternal exposure to a stressor on offspring performance at different life stages in a wild semelparous fish.

PubMed

Sopinka, N M; Hinch, S G; Middleton, C T; Hills, J A; Patterson, D A

2014-06-01

The environment mothers are exposed to has resonating effects on offspring performance. In iteroparous species, maternal exposure to stressors generally results in offspring ill-equipped for survival. Still, opportunities for future fecundity can offset low quality offspring. Little is known, however, as to how intergenerational effects of stress manifest in semelparous species with only a single breeding episode. Such mothers would suffer a total loss of fitness if offspring cannot survive past multiple life stages. We evaluated whether chronic exposure of female sockeye salmon (Oncorhynchus nerka) to a chase stressor impaired offspring performance traits. Egg size and early offspring survival were not influenced by maternal exposure to the repeated acute stressor. Later in development, fry reared from stressed mothers swam for shorter periods of time but possessed a superior capacity to re-initiate bouts of burst swimming. In contrast to iteroparous species, the mechanisms driving the observed effects do not appear to be related to cortisol, as egg hormone concentrations did not vary between stressed and undisturbed mothers. Sockeye salmon appear to possess buffering strategies that protect offspring from deleterious effects of maternal stress that would otherwise compromise progeny during highly vulnerable stages of development. Whether stressed sockeye salmon mothers endow offspring with traits that are matched or mismatched for survival in the unpredictable environment they encountered is discussed. This study highlights the importance of examining intergenerational effects among species-specific reproductive strategies, and across offspring life history to fully determine the scope of impact of maternal stress.

Oxidative Stress in Mouse Sperm Impairs Embryo Development, Fetal Growth and Alters Adiposity and Glucose Regulation in Female Offspring

PubMed Central

Lane, Michelle; McPherson, Nicole O.; Fullston, Tod; Spillane, Marni; Sandeman, Lauren; Kang, Wan Xian; Zander-Fox, Deirdre L.

2014-01-01

Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS) are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2), which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM) in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity. PMID:25006800

Effects of paternal high-fat diet and rearing environment on maternal investment and development of defensive responses in the offspring.

PubMed

Korgan, Austin C; O'Leary, Elizabeth; King, Jillian L; Weaver, Ian C G; Perrot, Tara S

2018-05-01

Paternal preconception risk factors (e.g. stress, diet, drug use) correlate with metabolic dysfunction in offspring, which is often comorbid with depressive and anxiety-like phenotypes. Detection of these risk factors or deleterious phenotypes informs a female about prevailing ecological demands, in addition to potential adverse environment-induced phenotypes that may be disseminated to her offspring. We examined whether a F 0 male rat's prior exposure to an obesogenic high-fat diet (HFD) influences a female's attraction towards a male, subsequent mother-infant interactions and the development of defensive (emotional) responses in the F 1 offspring. Females displayed less interest in the HFD exposed F 0 males relative to control diet-exposed F 0 males. Dams that reared F 1 offspring in larger, semi-naturalistic housing provided more licking and grooming and active arched-back-nursing behavior. However, some of these effects interacted with paternal experience. F 0 HFD and maternal rearing environment revealed sex-dependent, between group differences in F 1 offspring wean weight, juvenile social interactions and anxiety-like behavior in adolescence. Our results show for the first time in mammals that male exposure to HFD may contribute to stable behavioral variation among females in courtship, maternal care, even when the females are not directly exposed to a HFD, and anxiety-like behavior in F 1 offspring. Furthermore, when offspring were exposed to a predatory threat, hypothalamic Crf gene regulation was influenced by early housing. These results, together with our previous findings, suggest that paternal experience and maternal rearing conditions can influence maternal behavior and development of defensive responses of offspring. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Effect of maternal exposure to ozone on reproductive outcome and immune, inflammatory, and allergic responses in the offspring

EPA Science Inventory

There is growing concern that exposure to air pollutants during pregnancy affects health outcomes in the offspring due to alterations in the development of immune and other homeostatic processes. To assess the risks of maternal inhalation exposure to ozone (O3), timed pregnant BA...

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway.

PubMed

Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

2016-01-01

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995-97 and in 2006-08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents.

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway

PubMed Central

Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

2016-01-01

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995–97 and in 2006–08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents. PMID:27082110

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).

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism.

PubMed

Chen, Minjie; Liang, Shuai; Zhou, Huifen; Xu, Yanyi; Qin, Xiaobo; Hu, Ziying; Wang, Xiaoke; Qiu, Lianglin; Wang, Wanjun; Zhang, Yuhao; Ying, Zhekang

2017-01-18

Obesity is one of the leading threats to global public health. It is consequent to abnormal energy metabolism. Currently, it has been well established that maternal exposure to environmental stressors that cause inappropriate fetal development may have long-term adverse effects on offspring energy metabolism in an exposure timing-dependent manner, known as developmental programming of health and diseases paradigm. Rapidly increasing evidence has indicated that maternal exposure to ambient fine particles (PM 2.5 ) correlates to abnormal fetal development. In the present study, we therefore assessed whether maternal exposure to diesel exhaust PM 2.5 (DEP), the major component of ambient PM 2.5 in urban areas, programs offspring energy metabolism, and further examined how the timing of exposure impacts this programming. The growth trajectory of offspring shows that although prenatal maternal exposure to DEP did not impact the birth weight of offspring, it significantly decreased offspring body weight from postnatal week 2 until the end of observation. This weight loss effect of prenatal maternal exposure to DEP coincided with decreased food intake but not alteration in brown adipose tissue (BAT) morphology. The hypophagic effect of prenatal maternal exposure to DEP was in concord with decreased hypothalamic expression of an orexigenic peptide NPY, suggesting that the prenatal maternal exposure to DEP impacts offspring energy balance primarily through programming of food intake. Paradoxically, the reduced body weight resulted from prenatal maternal exposure to DEP was accompanied by increased mass of epididymal adipose tissue, which was due to hyperplasia as morphological analysis did not observe any hypertrophy. In direct contrast, the postnatal mothering by DEP-exposed dams increased offspring body weight during lactation and adulthood, paralleled by markedly increased fat accumulation and decreased UCP1 expression in BAT but not alteration in food intake. The weight gain induced by postnatal mothering by DEP-exposed dams was also expressed as an increased adiposity. But it concurred with a marked hypertrophy of adipocytes. Prenatal and postnatal mothering by DEP-exposed dams differentially program offspring energy metabolism, underscoring consideration of the exposure timing when examining the adverse effects of maternal exposure to ambient PM 2.5 .

A free-ranging, feral mare equus caballus affords similar maternal care to her genetic and adopted offspring.

PubMed

Nuñez, Cassandra M V; Adelman, James S; Rubenstein, Daniel I

2013-11-01

Adoption of nongenetic offspring occurs in a variety of species but is rare in equids. We report a case of adoption by a free-ranging, feral mare Equus caballus and compare the maternal care received by her genetic offspring (born 1995) to that of her adopted offspring (born 1996) for the first 30 weeks of development. We compare five measures of care: (1) total time spent suckling, (2) mare aggression during suckling, (3) number of mare-terminated suckling bouts, (4) contact maintenance, and (5) mare-foal distance. For most behaviors, we detected no difference in the mare's treatment of the two foals; however, mare-foal distance was greater for the genetic offspring. We compare hypotheses regarding the reasons for adoption, offering postpartum physiological state as a potential driver.

Maternal influences on early development: preferred temperature prior to oviposition hastens embryogenesis and enhances offspring traits in the Children's python, Antaresia childreni.

PubMed

Lorioux, Sophie; DeNardo, Dale F; Gorelick, Root; Lourdais, Olivier

2012-04-15

Embryonic life is particularly sensitive to its surroundings, and the developmental environment can have long-lasting effects on offspring. In oviparous species, the impacts of the developmental environment on offspring traits are mostly examined during development within the egg. However, as more than 25% of the development of squamate reptiles can occur prior to oviposition, we explored the effect of thermal conditions on development prior to oviposition in an oviparous snake species, the Children's python (Antaresia childreni). We housed gravid female pythons under three thermal cycles: an optimal regime that reflected maternal preference in a non-constrained environment (constant preferred body temperature of gravid females, T(set)=31.5°C) and two mildly suboptimal regimes that shared the same mean temperature of 27.7°C, but differed in the duration at T(set). In one of the constraining regimes, females had access to T(set) for 4 h daily whereas in the other regime, females never reached T(set) (maximal temperature of 29.0°C). Thermal treatments were maintained throughout gravidity in all three groups, but, after oviposition, all eggs were incubated at T(set) until hatching. Compared with the optimal regime, the two suboptimal regimes had a longer duration of gravidity, which resulted in delayed hatching. Between the two suboptimal regimes, gravidity was significantly shorter in the treatment that included time at T(set). Furthermore, suboptimal regimes influenced offspring traits at hatching, including body morphology, antipredator behavior, strength and metabolism. However, partial access to maternal T(set) significantly enhanced several offspring traits, including performance. Our results demonstrate the importance of time at T(set) on early development and suggest an adaptive significance of maternal thermoregulation prior to oviposition.

Photoperiodism of Male Offspring Production in the Water Flea Daphnia pulex.

PubMed

Toyota, Kenji; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

2017-08-01

Photoperiodism is a biological seasonal timing system utilized to regulate development and reproduction in organisms. The freshwater micro-crustacean Daphnia pulex displays environmental sex determination, the precise physiological mechanisms of which are largely unknown due to the lack of an experimental system to induce female or male offspring production by alterations of the rearing environment. We recently found that D. pulex, WTN6 strain, produces female or male offspring in response to long-day or short-day conditions, respectively. Taking advantage of this system, here we report the photoperiodic response curve for male offspring production, showing 12 hours as natural critical daylength (50% incidence of male-producing mothers), and that male offspring inducibility is highly sensitive to photoperiodic alterations. By using monochromatic light emitting diode (LED) devices, we found that the effective wavelength is red-light (627 nm), which stably induces male offspring production. This suggests that the red-light photoreceptor may be decisive in the primary step of sex determination process in this strain. Our findings provide the first insights into photoperiodism and red-light as key factors in triggering male offspring production in daphnids.

Effects of Paternal Predation Risk and Rearing Environment on Maternal Investment and Development of Defensive Responses in the Offspring

PubMed Central

Bauer, Jessica

2016-01-01

Abstract Detecting past experiences with predators of a potential mate informs a female about prevailing ecological threats, in addition to stress-induced phenotypes that may be disseminated to offspring. We examined whether prior exposure of a male rat to a predator (cat) odor influences the attraction of a female toward a male, subsequent mother–infant interactions and the development of defensive (emotional) responses in the offspring. Females displayed less interest in males that had experienced predator odor. Mothers that reared young in larger, seminaturalistic housing provided more licking and grooming and active arched back-nursing behavior toward their offspring compared with dams housed in standard housing, although some effects interacted with paternal experience. Paternal predation risk and maternal rearing environment revealed sex-dependent differences in offspring wean weight, juvenile social interactions, and anxiety-like behavior in adolescence. Additionally, paternal predator experience and maternal housing independently affected variations in crf gene promoter acetylation and crf gene expression in response to an acute stressor in offspring. Our results show for the first time in mammals that variation among males in their predator encounters may contribute to stable behavioral variation among females in preference for mates and maternal care, even when the females are not directly exposed to predator threat. Furthermore, when offspring were exposed to the same threat experienced by the father, hypothalamic crf gene regulation was influenced by paternal olfactory experience and early housing. These results, together with our previous findings, suggest that paternal stress exposure and maternal rearing conditions can influence maternal behavior and the development of defensive responses in offspring. PMID:27896313

Transmission of risk from parents with chronic pain to offspring: an integrative conceptual model.

PubMed

Stone, Amanda L; Wilson, Anna C

2016-12-01

Offspring of parents with chronic pain are at increased risk for pain and adverse mental and physical health outcomes (Higgins et al, 2015). Although the association between chronic pain in parents and offspring has been established, few studies have addressed why or how this relation occurs. Identifying mechanisms for the transmission of risk that leads to the development of chronic pain in offspring is important for developing preventive interventions targeted to decrease risk for chronic pain and related outcomes (eg, disability and internalizing symptoms). This review presents a conceptual model for the intergenerational transmission of chronic pain from parents to offspring with the goal of setting an agenda for future research and the development of preventive interventions. Our proposed model highlights 5 potential mechanisms for the relation between parental chronic pain and pediatric chronic pain and related adverse outcomes: (1) genetics, (2) alterations in early neurobiological development, (3) pain-specific social learning, (4), general parenting and family health, and (5) exposure to stressful environment. In addition, the model presents 3 potential moderators for the relation between parent and child chronic pain: (1) the presence of chronic pain in a second parent, (2) timing, course, and location of parental chronic pain, and (3) offspring's characteristics (ie, sex, developmental stage, race or ethnicity, and temperament). Such a framework highlights chronic pain as inherently familial and intergenerational, opening up avenues for new models of intervention and prevention that can be family centered and include at-risk children.

Prenatal stress accelerates offspring growth to compensate for reduced maternal investment across mammals

PubMed Central

Berghänel, Andreas; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

2017-01-01

Across mammals, prenatal maternal stress (PREMS) affects many aspects of offspring development, including offspring growth. However, how PREMS translates to offspring growth is inconsistent, even within species. To explain the full range of reported effects of prenatal adversity on offspring growth, we propose an integrative hypothesis: developmental constraints and a counteracting adaptive growth plasticity work in opposition to drive PREMS effects on growth. Mothers experiencing adversity reduce maternal investment leading to stunted growth (developmental constraints). Concomitantly, the pace of offspring life history is recalibrated to partly compensate for these developmental constraints (adaptive growth plasticity). Moreover, the relative importance of each process changes across ontogeny with increasing offspring independence. Thus, offspring exposed to PREMS may grow at the same rate as controls during gestation and lactation, but faster after weaning when direct maternal investment has ceased. We tested these predictions with a comparative analysis on the outcomes of 719 studies across 21 mammal species. First, the observed growth changes in response to PREMS varied across offspring developmental periods as predicted. We argue that the observed growth acceleration after weaning is not “catch-up growth,” because offspring that were small for age grew slower. Second, only PREMS exposure early during gestation produced adaptive growth plasticity. Our results suggest that PREMS effects benefit the mother’s future reproduction and at the same time accelerate offspring growth and possibly maturation and reproductive rate. In this sense, PREMS effects on offspring growth allow mother and offspring to make the best of a bad start. PMID:29180423

Demographic analysis of arrhenotokous parthenogenesis and bisexual reproduction of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae).

PubMed

Ding, Tianbo; Chi, Hsin; Gökçe, Ayhan; Gao, Yulin; Zhang, Bin

2018-02-20

Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) is a serious pest that is capable of bisexual and arrhenotokous reproduction. In arrhenotokous reproduction, virgin females initially produce male offspring; later, when their sons are sexually mature, the mothers begin bisexual reproduction by carrying out oedipal mating with their sons. Because a virgin female produces many male offspring before oedipal mating occurs, multiple oedipal mating is common. In this study, we investigated the effect of multiple oedipal mating on the population growth of F. occidentalis by using the age-stage, two-sex life table theory. In the arrhenotokous cohorts, all unfertilized eggs developed into males. In the bisexual cohorts, the offspring sex ratio was significantly female biased with the mean number of female offspring and male offspring being 72.68 and 29.00, respectively. These were the same as the net reproductive rate of female offspring and male offspring. In arrhenotokous cohorts, the number of males available for oedipal mating significantly affected the production of female offspring. The number of female offspring increased as the number of sons available for oedipal mating increased. Correctly characterizing this unique type of reproduction will provide important information for predicting the timing of future outbreaks of F. occidentalis, as well as aiding in formulating successful management strategies against the species.

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.

Paternal physical exercise demethylates the hippocampal DNA of male pups without modifying the cognitive and physical development.

PubMed

Mega, Filipe; de Meireles, André Luís Ferreira; Piazza, Francele Valente; Spindler, Christiano; Segabinazi, Ethiane; Dos Santos Salvalaggio, Gabriela; Achaval, Matilde; Marcuzzo, Simone

2018-08-01

Maternal exercise is known to have beneficial effects in progeny development, but the influence of paternal exercise on the offspring still unclear. Since spermatogenesis is a continuous process, the father's life experiences can reprogram epigenetic content of the sperm and somehow interfere on offspring phenotype. This study was designed to evaluate the effects of paternal physical exercise on cognitive and physical development and on hippocampal DNA methylation levels of the offspring. Adult male Wistar rats were divided into two groups: sedentary and exercised. The exercise protocol occurred before mating and consisted of treadmill running, 5 consecutive days/week for 8 weeks (20 min/day). The mothers were not trained. The following developmental parameters were examined in male offspring: body growth, physical and cognitive performance, weights of adrenal glands, gonadal fat and hindlimb muscles, BDNF expression and global DNA methylation at the hippocampus. The progeny of trained and sedentary fathers did not differ in relation to physical parameters and performance, spatial memory and BDNF expression. However, paternal exercise promoted a decrease in offspring´s relative gonadal fat weight and a lower percentage of global hippocampal DNA methylation compared to offspring of sedentary fathers. These results pointed to interference of male physical activity at the time of conception on adiposity and hippocampal epigenetic reprogramming of male offspring. The data reinforces that exercise does not harm the descendant's development and emphasize the benefits to include the practice of physical exercise in a healthier lifestyle of the parents. Nevertheless, future studies are necessary and should investigate further the long-effects of epigenetic mechanisms in order to elucidate the father's contribution in fetal programming. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of prenatal /sup 60/Co irradiation on postnatal neural, learning, and hormonal development of the squirrel monkey

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

Ordy, J.M.; Brizzee, K.R.; Dunlap, W.P.

1982-02-01

The goals of this study were to examine the effects of 0, 50, and 100 rad of /sup 60/Co administered prenatally on postnatal development of neuromuscular coordination, visual discrimination learning, spontaneous light-dark stabilimeter activity, plasma cortisol, and somatometric growth rates of diurnal squirrel monkeys from birth to 90 days. In terms of accuracy, completeness, and time required for performance of reflexes and neuromuscular coordination, the performance of 50- and 100-rad offspring was less accurate and poorly coordinated and required more time for completion to that of controls. In visual orientation, discrimination, and reversal learning, the percentage correct responses of themore » 50- and 100-rad offspring were significantly lower than those of controls. Spontaneous light-dark stabilimeter activity of 50- and 100-rad offspring was significantly higher in the dark session than that of controls. Plasma cortisol was significantly higher in 100-rad infants than in controls. Comparisons of somatometric growth rates indicated that postnatal head circumference, crown-rump length, and to a lesser extent body weight increased at significantly slower rates in 50- and 100-rad offspring. These findings should provide essential information for formulating and carrying out multivariate behavioral, biochemical, and morphometric assessments of low-dose effects on the brain of primate offspring within demonstrable dose-response curves.« less

Long-life partners or sex friends? Impact of parental pair bond on offspring personality.

PubMed

Le Bot, Océane; Lumineau, Sophie; de Margerie, Emmanuel; Pittet, Florent; Trabalon, Marie; Houdelier, Cécilia

2014-12-01

Previous investigations reported that some traits of parental relationships, including pair-bond duration or mate behavioural compatibility, influence subsequent offspring fitness by acting on their behaviour and growth and thus their early survival. We hypothesized that the development of a pair bond between sexual partners would have a prenatal influence. This study investigated the impact of two pairing managements on the egg characteristics and development of offspring of Japanese quail (Coturnix c. japonica). Thirty males and 30 females were paired either continuously (C; mates together all the time) or non-continuously (NC; pairs met only three times a week for 5 min). Separation-reunion tests evaluated parental pair bond. Egg yolk testosterone and androstenedione levels were evaluated, and the somatic and behavioural development of C and NC chicks was assessed. Our results revealed that members of C pairs were attached to their mates and, although no significant differences in androgen levels could be evidenced between egg sets, a higher proportion of C pairs' eggs were fertilized and their chicks appeared less emotive and more social. Our results revealed that the parental relationship can modulate the behavioural development of their offspring, probably via non-genetic effects, and this could play a major role in the emergence of inter-individual variability. © 2014. Published by The Company of Biologists Ltd.

Attention-deficit/hyperactivity disorder (ADHD) and motor timing in adolescents and their parents: familial characteristics of reaction time variability vary with age.

PubMed

Thissen, Andrieke J A M; Luman, Marjolein; Hartman, Catharina; Hoekstra, Pieter; van Lieshout, Marloes; Franke, Barbara; Oosterlaan, Jaap; Rommelse, Nanda N J; Buitelaar, Jan K

2014-09-01

There is consistent evidence that attention-deficit/hyperactivity disorder (ADHD) is strongly related to impaired motor timing as reflected in decreased accuracy and increased reaction time variability (RTV). It is not known whether motor timing impairments are present in adolescents and adults with ADHD and their unaffected relatives to the same extent as has been reported in children, and whether ADHD and motor timing share familial underpinnings, as reflected in parent-offspring co-segregation and sibling cross-correlations. A total of 589 parents and 808 children/adolescents from families with ADHD and control families (parent/offspring average age: 48.6/17.3 years) were included. All participants were thoroughly assessed for ADHD and performed a 40-trial motor timing task (1-second interval production). Dependent neurocognitive measures included RT median (RTM: representing accuracy), RTV and ex-Gaussian component τ (τ: representing infrequent long response times). Generalized estimating equations were used for analyses. Unaffected children from families with ADHD had RTV (but not RTM or τ) scores in between those of affected and control children. However, during middle-to-late adolescence, unaffected offspring were not impaired compared to control offspring and differed from ADHD probands, whereas during late adolescence/early adulthood, all offspring groups performed equally. Affected and unaffected parents of families with ADHD showed increased RTV compared to controls, regardless of age (not significant after adjusting for IQ). There were indications for shared familiality between RTV and ADHD as reflected by sibling cross-correlations and between RTM and ADHD as reflected by sibling cross-correlations and a maternal parent-offspring relation (parent-of-origin effect). RTV and its familial characteristics are influenced by development during adolescence. Increased RTV in children with ADHD appears to reflect immaturities in their neurocognitive functioning. Maternal ADHD effects might be involved in transmission of RTM (not RTV), but overall RTM showed less compelling (familial) relationships with ADHD than RTV. Copyright © 2014. Published by Elsevier Inc.

Effects of maternal cortisol treatment on offspring size, responses to stress, and anxiety-related behavior in wild largemouth bass (Micropterus salmoides).

PubMed

Redfern, Julia C; Cooke, Steven J; Lennox, Robert J; Nannini, Michael A; Wahl, David H; Gilmour, Kathleen M

2017-10-15

Cortisol, the main glucocorticoid stress hormone in teleost fish, is of interest as a mediator of maternal stress on offspring characteristics because it plays an organizational role during early development. The present study tested the hypothesis that maternal exposure to cortisol treatment prior to spawn affects offspring phenotype using wild largemouth bass (Micropterus salmoides). Baseline and stress-induced cortisol concentrations, body size (i.e. length and mass), and behavior (i.e. anxiety, exploration, boldness, and aggression) were assessed at different offspring life-stages and compared between offspring of control and cortisol-treated females. Cortisol administration did not affect spawning success or timing, nor were whole-body cortisol concentrations different between embryos from cortisol-treated and control females. However, maternal cortisol treatment had significant effects on offspring stress responsiveness, mass, and behavior. Compared to offspring of control females, offspring of cortisol-treated females exhibited larger mass right after hatch, and young-of-the-year mounted an attenuated cortisol response to an acute stressor, and exhibited less thigmotaxic anxiety, exploratory behavior, boldness and aggression. Thus, offspring phenotype was affected by elevated maternal cortisol levels despite the absence of a significant increase in embryo cortisol concentrations, suggesting that a mechanism other than the direct deposition of cortisol into eggs mediates effects on offspring. The results of the present raise questions about the mechanisms through which maternal stress influences offspring behavior and physiology, as well as the impacts of such phenotypic changes on offspring fitness. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial variation in pollinator gall failure within figs of the gynodioecious Ficus hirta

NASA Astrophysics Data System (ADS)

Yu, Hui; Compton, Stephen G.; Wu, Lanfen

2018-07-01

Figs, the inflorescences of Ficus species (Moraceae), contain numerous uni-ovulate flowers. Male trees of gynodioecious Ficus have figs that support development of pollinator fig wasp offspring (Agaonidae) and rarely produce seeds. Pollinator larvae develop inside galled ovules that expand rapidly after eggs are laid to fill the available space. Galls that fail to support successful larval development can be abundant and failures may influence oviposition behavior and modify realized offspring sex ratios. We examined pollinator reproductive success in figs of the Asian Ficus hirta where we had allowed entry by either one or two foundresses and prevented attack by parasitoids. At the developmental stage when adult offspring were about to emerge from their galls, we recorded where in the figs their galls were located, the distributions of sons and daughters in the galls and whether galls that developed closest to the periphery of the figs were more likely to fail. Foundress number had an effect on gall location, but not total offspring numbers. No spatial variation in the distribution of male and female adult offspring was detected. Overall, over 25% of the galled ovaries failed to support offspring development, and failure rates were independent of foundress number. More peripheral galls were more likely to fail in figs entered by two foundresses. Gall location in gynodioecious figs is determined largely by the extent to which their basal pedicels expand after galling. Competition for nutrients between galls, with those developing shorter pedicels being at a disadvantage, may explain the results. If pedicel length is related to timing of oviposition, then pollinator eggs laid later are less likely to survive.

Effects of tartrazine on exploratory behavior in a three-generation toxicity study in mice.

PubMed

Tanaka, Toyohito; Takahashi, Osamu; Oishi, Shinshi; Ogata, Akio

2008-10-01

Tartrazine was given to mice in the diet at levels of 0 (control), 0.05%, 0.15%, and 0.45% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(2) generation, and selected reproductive and neurobehavioral parameters were measured. In the F(1) generation, the development of swimming direction at postnatal day (PND) 7 was accelerated significantly in male offspring in a dose-related manner. Surface righting at PND 7 was affected significantly in female offspring in dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age. In the F(2) generation, the development of swimming direction at PND 7 was accelerated significantly in the high-dosed group in male offspring. Time taken of olfactory orientation at PND 14 was accelerated significantly in male offspring in a dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age, and in males at 8 weeks of age. The dose levels of tartrazine in the present study produced a few adverse effects on neurobehavioral parameters throughout generations in mice.

Effects of maternal exposure to bisphenol AF on emotional behaviors in adolescent mice offspring.

PubMed

Gong, Miao; Huai, Ziqing; Song, Han; Cui, Lingyu; Guo, Qingjun; Shao, Juan; Gao, Yuan; Shi, Haishui

2017-11-01

Exposure to bisphenol A (BPA), one kind of environmental endocrine disruptors (EEDs), exerted significantly detrimental effects on neuro-endocrinological system and related disorders, such as memory dysfunction and depression. Bisphenol AF (BPAF),a newly introduced chemical structurally related to BPA, is used extensively. BPAF has stronger estrogenic activities than BPA. However, the potential neurotoxicological effects of BPAF are still elusive. The present study aimed to investigate the potential effects of maternal BPAF exposure during pregnancy on emotional behaviors of adolescent mice offspring. In male adolescent offspring, maternal exposure to BPAF (0.4, 4.0 mg kg -1 , intragastrically administration) induced significant anxiety- and depressive-like behaviors, assessed by open field test (OFT), novelty-suppressed feeding test (NSF), sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST). In female adolescent offspring, BPAF exposure at 0.4 mg kg -1 dose reduced the latency to feeding in the NSF test, while increased the floating time in the FST. Maternal BPAF exposure decreased the recognition index in the long term memory (LTM) test in both sexes, while only decreased the freezing time of male offspring in the contextual fear conditioning (CFC) task. These results indicate that maternal exposure to BPAF significantly affect emotion-related behaviors in adolescent mice offspring, and the male offspring with a higher probability to develop symptoms of anxiety and depression and to suffer memory impairment after maternal exposure to BPAF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal effects on offspring stress physiology in wild chimpanzees.

PubMed

Murray, Carson M; Stanton, Margaret A; Wellens, Kaitlin R; Santymire, Rachel M; Heintz, Matthew R; Lonsdorf, Elizabeth V

2018-01-01

Early life experiences are known to influence hypothalamic-pituitary-adrenal (HPA) axis development, which can impact health outcomes through the individual's ability to mount appropriate physiological reactions to stressors. In primates, these early experiences are most often mediated through the mother and can include the physiological environment experienced during gestation. Here, we investigate stress physiology of dependent offspring in wild chimpanzees for the first time and examine whether differences in maternal stress physiology are related to differences in offspring stress physiology. Specifically, we explore the relationship between maternal rank and maternal fecal glucocorticoid metabolite (FGM) concentration during pregnancy and early lactation (first 6 months post-partum) and examine whether differences based on maternal rank are associated with dependent offspring FGM concentrations. We found that low-ranking females exhibited significantly higher FGM concentrations during pregnancy than during the first 6 months of lactation. Furthermore, during pregnancy, low-ranking females experienced significantly higher FGM concentrations than high-ranking females. As for dependent offspring, we found that male offspring of low-ranking mothers experienced stronger decreases in FGM concentrations as they aged compared to males with high-ranking mothers or their dependent female counterparts. Together, these results suggest that maternal rank and FGM concentrations experienced during gestation are related to offspring stress physiology and that this relationship is particularly pronounced in males compared to females. Importantly, this study provides the first evidence for maternal effects on the development of offspring HPA function in wild chimpanzees, which likely relates to subsequent health and fitness outcomes. Am. J. Primatol. 80:e22525, 2018. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

Selection for rapid embryo development correlates with embryo exposure to maternal androgens among passerine birds

USGS Publications Warehouse

Schwabl, H.; Palacios, M.G.; Martin, T.E.

2007-01-01

Greater offspring predation favors evolution of faster development among species. We hypothesized that greater offspring predation exerts selection on mothers to increase levels of anabolic androgens in egg yolks to achieve faster development. Here, we tested whether (1) concentrations of yolk androgens in passerine species were associated with offspring predation and (2) embryo and nestling development rates were associated with yolk androgen concentrations. We examined three androgens that increase in potency along the synthesis pathway: androstenedione (A4) to testosterone (T) to 5??- dihydrotestosterone (5??-DHT). Concentrations of none of these steroids were related to clutch size; only A4 was allometrically related to egg volume. Species that experience greater predation showed higher yolk concentrations of T and 5??-DHT. Higher concentrations of T and particularly 5??-DHT were strongly correlated with faster development during the embryo period and less so during the nestling period. Development rates were most strongly correlated with 5??-DHT, suggesting that potency increases along the androgen synthesis pathway and that effects are mediated by the androgen receptor pathway. These results are consistent with the hypothesis that selection for faster development by time-dependent offspring mortality may be achieved epigenetically by varying embryo exposure to maternal anabolic steroids. ?? 2007 by The University of Chicago. All rights reserved.

Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice.

PubMed

Maruoka, Takashi; Kodomari, Ikuko; Yamauchi, Rena; Wada, Etsuko; Wada, Keiji

2009-04-17

The maternal environment is thought to be important for fetal brain development. However, the effects of maternal environment are not fully understood. Here, we investigated whether enrichment of the maternal environment can influence prenatal brain development and postnatal behaviors in mice. An enriched environment is a housing condition with several objects such as a running wheel, tube and ladder, which are thought to increase sensory, cognitive and motor stimulation in rodents compared with standard housing conditions. First, we measured the number of BrdU-positive cells in the hippocampal dentate gyrus of fetuses from pregnant dams housed in an enriched environment. Our results revealed that maternal enrichment influences cell proliferation in the hippocampus of female, but not male, fetuses. Second, we used the open-field test to investigate postnatal behaviors in the offspring of dams housed in the enriched environment during pregnancy. We found that maternal enrichment significantly affects the locomotor activity and time spent in the center of the open-field in female, but not male, offspring. These results indicate that maternal enrichment influences prenatal brain development and postnatal behaviors in female offspring.

Regulation of Baboon Fetal Ovarian Development by Placental Estrogen: Onset of Puberty Is Delayed in Offspring Deprived of Estrogen In Utero1

PubMed Central

Pepe, Gerald J.; Lynch, Terrie J.; Albrecht, Eugene D.

2013-01-01

ABSTRACT Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen. PMID:24132960

Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero.

PubMed

Pepe, Gerald J; Lynch, Terrie J; Albrecht, Eugene D

2013-12-01

Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen.

A mathematical model on the optimal timing of offspring desertion.

PubMed

Seno, Hiromi; Endo, Hiromi

2007-06-07

We consider the offspring desertion as the optimal strategy for the deserter parent, analyzing a mathematical model for its expected reproductive success. It is shown that the optimality of the offspring desertion significantly depends on the offsprings' birth timing in the mating season, and on the other ecological parameters characterizing the innate nature of considered animals. Especially, the desertion is less likely to occur for the offsprings born in the later period of mating season. It is also implied that the offspring desertion after a partially biparental care would be observable only with a specific condition.

The interval between cancer diagnosis among mothers and offspring in a population-based cohort.

PubMed

Paltiel, Ora; Friedlander, Yehiel; Deutsch, Lisa; Yanetz, Rebecca; Calderon-Margalit, Ronit; Tiram, Efrat; Hochner, Hagit; Barchana, Micha; Harlap, Susan; Manor, Orly

2007-01-01

Familial cancers may be due to shared genes or environment, or chance aggregation. We explored the possibility that ascertainment bias influences cancer detection in families, bearing upon the time interval between diagnosis of affected mothers and offspring. The Jerusalem Perinatal Study (JPS) comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 -1976 and their offspring (n = 88,829). After linking identification numbers with Israel's Cancer Registry we measured the absolute time interval between initial cancer diagnoses in affected mother-offspring pairs. We tested the probability of obtaining intervals as short as those observed by chance alone, using a permutation test on the median interval. By June 2003 cancer had developed in 105 mother-offspring pairs within the cohort. Common sites among mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and cervix (7%), while for offspring in affected pairs common cancers were leukemia (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The median interval between diagnoses was 5.9 years, but for 33% of affected pairs the interval was < or =3 years. The probability of this occurring by chance alone was 0.03. This held true whether the offspring's or mother's diagnosis was first (P < 0.01). In a population-based cohort followed for three decades, the absolute interval between the diagnosis of cancer in mothers and their offspring is shorter than expected by chance. Explanations include shared environmental exposures or the possibility that cancer ascertainment in one pair member affects health behaviors in the other resulting in early diagnosis. The latter may bias the estimation of anticipation and survival in familial cancers.

Reversal of prenatal morphine exposure-induced memory deficit in male but not female rats.

PubMed

Nasiraei-Moghadam, Shiva; Sherafat, Mohammad Amin; Safari, Mir-Shahram; Moradi, Fatemeh; Ahmadiani, Abolhassan; Dargahi, Leila

2013-05-01

Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M₁₋₁₃, or to the time of delivery, M₁₋₂₁. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M₁₋₁₃ and M₁₋₂₁ groups. Adolescent and adult male offspring were similar to control animals in M₁₋₁₃ group. However M₁₋₂₁ impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M₁₋₁₃ and M₁₋₂₁ adolescent and adult female rats, but only in M₁₋₂₁ adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.

2,4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide.

PubMed

Fujiwara, Reiko; Sasajima, Naho; Takemura, Naoki; Ozawa, Keisuke; Nagasaka, Yuki; Okubo, Takuma; Sahasakul, Yuraporn; Watanabe, Jun; Sonoyama, Kei

2010-01-01

Strategies to manipulate gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We previously demonstrated that maternal dietary supplementation with fructo-oligosaccharide (FOS) during pregnancy and lactation modulated the composition of gut microbiota and diminished the severity of spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. The present study tested whether dietary FOS affects contact hypersensitivity (CHS), another model for allergic skin disease, in NC/Nga mice. In experiment 1, 5-wk-old female NC/Nga mice were fed diets either with or without FOS supplementation for 3 wk and then received 2,4-dinitrofluorobenzene (DNFB) on the ear auricle 5 times at 7-d intervals. FOS supplementation reduced CHS response as demonstrated by ear swelling. Quantitative RT-PCR analysis showed that mRNA levels for interleukin (IL)-10, IL-12p40, and IL-17 in the lesional ear skin were significantly lower in mice fed FOS. In experiment 2, female NC/Nga mice were fed diets either with or without FOS during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without FOS. Three weeks after weaning, offspring received DNFB on the ear auricle 4 times at 7-d intervals. Although FOS supplementation after weaning reduced ear swelling, maternal FOS consumption was ineffective in offspring. The present data suggest that dietary FOS reduces CHS while maternal FOS consumption is ineffective in offspring of DNFB-treated NC/Nga mice.

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.

Variation in maternal effects and embryonic development rates among passerine species

USGS Publications Warehouse

Martin, T.E.; Schwabl, H.

2008-01-01

Embryonic development rates are reflected by the length of incubation period in birds, and these vary substantially among species within and among geographical regions. The incubation periods are consistently shorter in North America (Arizona study site) than in tropical (Venezuela) and subtropical (Argentina) South America based on the study of 83 passerine species in 17 clades. Parents, mothers in particular, may influence incubation periods and resulting offspring quality through proximate pathways, while variation in maternal strategies among species can result from selection by adult and offspring mortality. Parents of long-lived species, as is common in the tropics and subtropics, may be under selection to minimize costs to themselves during incubation. Indeed, time spent incubating is often lower in the tropical and subtropical species than the related north temperate species, causing cooler average egg temperatures in the southern regions. Decreased egg temperatures result in longer incubation periods and reflect a cost imposed on offspring by parents because energy cost to the embryo and risk of offspring predation are both increased. Mothers may adjust egg size and constituents as a means to partially offset such costs. For example, reduced androgen concentrations in egg yolks may slow development rates, but may enhance offspring quality through physiological trade-offs that may be particularly beneficial in longer-lived species, as in the tropics and subtropics. We provide initial data to show that yolks of tropical birds contain substantially lower concentrations of growth-promoting androgens than north temperate relatives. Thus, maternal (and parental) effects on embryonic development rates may include contrasting and complementary proximate influences on offspring quality and deserve further field study among species. ?? 2007 The Royal Society.

Maternal treatment of rats with the new pyridoindole antioxidant during pregnacy and lactation resulting in improved offspring hippocampal resistance to ischemia in vitro.

PubMed

Gáspárová, Zdenka; Snirc, Vladimír; Stolc, Svorad; Dubovický, Michal; Mach, Mojmír; Ujházy, Eduard

2010-01-01

Damage to the developing brain may be caused by maternal environment, nutritional deficiencies, failure of protective mechanisms, etc. Further, the developing brain may be damaged by intrauterine ischemia or by ischemia in newborns complicated by perinatal asphyxia. There is an effort to find agents with neuroprotective effect on the developing brain. The aim was to study the effect of the new pyridoindole antioxidant SMe1EC2 on the resistance of offspring hippocampus exposed to ischemia in vitro after treatment of mothers. The electrically evoked responses were determined by extracellular recording from offspring hippocampal slices. The effect of oral treatment of rats with SMe1EC2 over 18 consecutive days, from day 15 of gestation to day 10 post partum (PP) was analyzed in the model of ischemia in vitro measured on the hippocampus of 21-day-old pups, with focus on neuronal function recovery in reoxygenation. Increased recovery of neuronal response was found at the end of 20-min reoxygenation in offspring hippocampal slices exposed to 10-min hypoxia/hypoglycemia from rats whose mothers were treated with the dose of 50 and 250 mg/kg of SMe1EC2, compared to control offspring slices (mothers received vehicle over the same time). The increased offspring hippocampus resistance to hypoxia/hypoglycemia due to 18-day maternal treatment with SMe1EC2 might have been obtained via the transplacental way as well as in the neonatal period via breast milk, skin and saliva. The manifested neuroprotective effect of SMe1EC2 on the developing brain might find exploitation during risk pregnancy and delivery.

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.

Variation in maternal effects and embryonic development rates among passerine species.

PubMed

Martin, Thomas E; Schwabl, Hubert

2008-05-12

Embryonic development rates are reflected by the length of incubation period in birds, and these vary substantially among species within and among geographical regions. The incubation periods are consistently shorter in North America (Arizona study site) than in tropical (Venezuela) and subtropical (Argentina) South America based on the study of 83 passerine species in 17 clades. Parents, mothers in particular, may influence incubation periods and resulting offspring quality through proximate pathways, while variation in maternal strategies among species can result from selection by adult and offspring mortality. Parents of long-lived species, as is common in the tropics and subtropics, may be under selection to minimize costs to themselves during incubation. Indeed, time spent incubating is often lower in the tropical and subtropical species than the related north temperate species, causing cooler average egg temperatures in the southern regions. Decreased egg temperatures result in longer incubation periods and reflect a cost imposed on offspring by parents because energy cost to the embryo and risk of offspring predation are both increased. Mothers may adjust egg size and constituents as a means to partially offset such costs. For example, reduced androgen concentrations in egg yolks may slow development rates, but may enhance offspring quality through physiological trade-offs that may be particularly beneficial in longer-lived species, as in the tropics and subtropics. We provide initial data to show that yolks of tropical birds contain substantially lower concentrations of growth-promoting androgens than north temperate relatives. Thus, maternal (and parental) effects on embryonic development rates may include contrasting and complementary proximate influences on offspring quality and deserve further field study among species.

Centenarian offspring: start healthier and stay healthier.

PubMed

Adams, Emily R; Nolan, Vikki G; Andersen, Stacy L; Perls, Thomas T; Terry, Dellara F

2008-11-01

To assess the relative incidence of age-related diseases in a group of centenarian offspring who have thus far been considered to be predisposed to "healthy" aging. Longitudinal study. Nationwide sample. Four hundred forty centenarian offspring and 192 referent cohort subjects who met inclusion criteria of having initial and follow-up health questionnaire data available. Median age of both cohorts was 72 at the initial health questionnaire. Initial health questionnaires were collected from 1997 to 2006. Follow-up questionnaires were collected from 2004 to 2007. The mean period of follow-up was 3.5+/-1.7 years for the centenarian offspring and 3.9+/-2.2 years for the referent cohort. During the follow-up period, centenarian offspring had a 78% lower risk of myocardial infarction (P<.04), 83% lower risk of stroke (P<.004), and 86% lower risk of developing diabetes mellitus (P<.005) than the referent cohort. There were no significant differences in new onset of other age-related diseases. Additionally, centenarian offspring were 81% less likely to die (P<.01) than the referent cohort during the follow-up. These findings suggest that centenarian offspring retain some important cardiovascular advantages over time over similarly aged referent cohort subjects. These findings reinforce the notion that there may be physiological reasons that longevity runs in families and that centenarian offspring are more likely to age in better cardiovascular health and with a lower mortality than their peers.

Transmission of risk from parents with chronic pain to offspring: an integrative conceptual model

PubMed Central

Stone, Amanda L.; Wilson, Anna C.

2017-01-01

Offspring of parents with chronic pain are at increased risk for pain and adverse mental and physical health outcomes (Higgins et al, 2015). Although the association between chronic pain in parents and offspring has been established, few studies have addressed why or how this relation occurs. Identifying mechanisms for the transmission of risk that leads to the development of chronic pain in offspring is important for developing preventive interventions targeted to decrease risk for chronic pain and related outcomes (eg, disability and internalizing symptoms). This review presents a conceptual model for the intergenerational transmission of chronic pain from parents to offspring with the goal of setting an agenda for future research and the development of preventive interventions. Our proposed model highlights 5 potential mechanisms for the relation between parental chronic pain and pediatric chronic pain and related adverse outcomes: (1) genetics, (2) alterations in early neurobiological development, (3) pain-specific social learning, (4), general parenting and family health, and (5) exposure to stressful environment. In addition, the model presents 3 potential moderators for the relation between parent and child chronic pain: (1) the presence of chronic pain in a second parent, (2) timing, course, and location of parental chronic pain, and (3) offspring’s characteristics (ie, sex, developmental stage, race or ethnicity, and temperament). Such a framework highlights chronic pain as inherently familial and intergenerational, opening up avenues for new models of intervention and prevention that can be family centered and include at-risk children. PMID:27380502

No evidence for sex-specific effects of the maternal social environment on offspring development in Japanese quail (Coturnix japonica).

PubMed

Langen, Esther M A; von Engelhardt, Nikolaus; Goerlich-Jansson, Vivian C

2018-07-01

The social environment of reproducing females can cause physiological changes, with consequences for reproductive investment and offspring development. These prenatal maternal effects are often found to be sex-specific and may have evolved as adaptations, maximizing fitness of male and female offspring for their future environment. Female hormone levels during reproduction are considered a potential mechanism regulating sex allocation in vertebrates: high maternal androgens have repeatedly been linked to increased investment in sons, whereas high glucocorticoid levels are usually related to increased investment in daughters. However, results are not consistent across studies and therefore still inconclusive. In Japanese quail (Coturnix japonica), we previously found that pair-housed females had higher plasma androgen levels and tended to have higher plasma corticosterone levels than group-housed females. In the current study we investigate whether these differences in maternal social environment and physiology affect offspring sex allocation and physiology. Counter to our expectations, we find no effects of the maternal social environment on offspring sex ratio, sex-specific mortality, growth, circulating androgen or corticosterone levels. Also, maternal corticosterone or androgen levels do not correlate with offspring sex ratio or mortality. The social environment during reproduction therefore does not necessarily modify sex allocation and offspring physiology, even if it causes differences in maternal physiology. We propose that maternal effects of the social environment strongly depend upon the type of social stimuli and the timing of changes in the social environment and hormones with respect to the reproductive cycle and meiosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Associations between postnatal maternal depression and psychological outcomes in adolescent offspring: a systematic review.

PubMed

Sanger, Camilla; Iles, Jane E; Andrew, Catharina S; Ramchandani, Paul G

2015-04-01

Postnatal depression (PND) affects approximately 10-20 % of new mothers in developed countries, with accumulating research documenting its adverse impact on not only the mother but also the wider family. Longitudinal studies assessing potential effects of maternal PND on offspring are mounting, and it is therefore timely to investigate the long-term psychological outcomes for adolescent offspring who were exposed to PND in infancy. PsycINFO, Medline, and Embase databases were searched with key terms for English language abstracts. Papers of 16 were identified that examined associations between PND and internalising problems, externalising problems, psychopathology, psychosocial, and cognitive outcomes of adolescent offspring. Impaired offspring cognitive outcomes reflected some of the most consistent findings. Conflicting evidence was found for an effect of PND on adolescent offspring internalising and externalising problems and overall psychopathology. Psychosocial outcomes in offspring adolescents indicated a specific adverse effect, although based on only two studies. Significant gender differences across outcomes were found. It was concluded that PND possibly increases risk vulnerability in the presence of recurrent, concurrent, and antenatal maternal depression but that these latter factors alone may be the stronger specific predictors. Limitations of the review are discussed as well as implications for future research and clinical practice.

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.

Maternal effects of the English grain aphids feeding on the wheat varieties with different resistance traits.

PubMed

Hu, Xiang-Shun; Zhang, Zhan-Feng; Zhu, Tong-Yi; Song, Yue; Wu, Li-Juan; Liu, Xiao-Feng; Zhao, Hui-Yan; Liu, Tong-Xian

2018-05-09

The maternal effects of the English grain aphid, Sitobion avenae on offspring phenotypes and performance on wheat varieties with different resistance traits were examined. We found that both conditioning wheat varieties(the host plant for over 3 months) and transition wheat varieties affected the biological parameters of aphid offspring after they were transferred between wheat varieties with different resistance traits. The conditioning varieties affected weight gain, development time (DT), and the intrinsic rate of natural increase (r m ), whereas transition varieties affected the fecundity, r m , net reproductive rate, and fitness index. The conditioning and transition wheat varieties had significant interaction effects on the aphid offspring's DT, mean relative growth rate, and fecundity. Our results showed that there was obvious maternal effects on offspring when S. avenae transferred bwteen wheat varieties with different resistance level, and the resistance traits of wheat varieties could induce an interaction between the conditioning and transition wheat varieties to influence the growth, development, reproduction, and even population dynamics of S. avenae. The conditioning varieties affected life-history traits related to individual growth and development to a greater extent, whereas transition varieties affected fecundity and population parameters more.

Effects of paternal phenotype and environmental variability on age and size at maturity in a male dimorphic mite

NASA Astrophysics Data System (ADS)

Smallegange, Isabel M.

2011-04-01

Investigating how the environment affects age and size at maturity of individuals is crucial to understanding how changes in the environment affect population dynamics through the biology of a species. Paternal phenotype, maternal, and offspring environment may crucially influence these traits, but to my knowledge, their combined effects have not yet been tested. Here, I found that in bulb mites ( Rhizoglyphus robini), maternal nutrition, offspring nutrition, and paternal phenotype (males are fighters, able to kill other mites, or benign scramblers) interactively affected offspring age and size at maturity. The largest effect occurred when both maternal and offspring nutrition was poor: in that case offspring from fighter sires required a significantly longer development time than offspring from scrambler sires. Investigating parental effects on the relationship between age and size at maturity revealed no paternal effects, and only for females was its shape influenced by maternal nutrition. Overall, this reaction norm was nonlinear. These non-genetic intergenerational effects may play a complex, yet unexplored role in influencing population fluctuations—possibly explaining why results from field studies often do not match theoretical predictions on maternal effects on population dynamics.

Ephemeral clonal integration in Calathea marantifolia (Marantaceae): Evidence of diminished integration over time.

PubMed

Matlaga, David P; da S L Sternberg, Leonel

2009-02-01

A major advantage of clonal growth forms is the intergenerational transfer of resources through vascular connections (clonal integration). Connections linking ramets can be persistent or ephemeral. For species with ephemeral connections, whether the extent of clonal integration changes over time is unclear. To address this issue, we tracked water movement using an isotopic label and assessed the demographic performance of parent and offspring ramets over time in a severing experiment. Our study system was the understory herb Calathea marantifolia, which has parent ramets that produce vegetative bulbils (clonal offspring) that pass through distinct pre- and post-rooting stages. Little water was transported between parents and offspring, and the direction of movement was primarily from parent to pre-rooting offspring. Anatomical observations of inter-ramet connections showed that vascular bundles were twice as abundant in parent stems compared to inter-ramet connections. Severing inter-ramet connections reduced the growth of offspring ramets but not parents. Survival of pre-rooting offspring was reduced by 10% due to severing, but post-rooting offspring were not affected. Our results suggest that offspring ramets of C. marantifolia are weaned from their parent as they progress from pre- to post-rooting stages.

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-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production.

Revealing Behavioral Learning Deficit Phenotypes Subsequent to In Utero Exposure to Benzo(a)pyrene

PubMed Central

McCallister, Monique M.; Li, Zhu; Zhang, Tongwen; Ramesh, Aramandla; Clark, Ryan S.; Maguire, Mark; Hutsell, Blake; Newland, M. Christopher; Hood, Darryl B.

2016-01-01

To characterize behavioral deficits in pre-adolescent offspring exposed in utero to Benzo(a)pyrene [B(a)P], timed-pregnant Long Evans Hooded rats were treated with B(a)P (150, 300, 600, and 1200 µg/kg BW) or peanut oil (vehicle) on E14, 15, 16, and 17. Following birth, during the pre-weaning period, B(a)P metabolites were examined in plasma and whole brain or cerebral cortex from exposed and control offspring. Tissue concentrations of B(a)P metabolites were (1) dose-dependent and (2) followed a time-dependence for elimination with ∼60% reduction by PND5 in the 1200 µg/kg BW experimental group. Spatial discrimination-reversal learning was utilized to evaluate potential behavioral neurotoxicity in P40–P60 offspring. Late-adolescent offspring exposed in utero to 600 and 1200 µg/kg BW were indistinguishable from their control counterparts for ability to acquire an original discrimination (OD) and reach criterion. However, a dose-dependent effect of in utero B(a)P-exposure was evident upon a discrimination reversal as exposed offspring perseverated on the previously correct response. This newly characterized behavioral deficit phenotype for the first reversal was not apparent in either the (1) OD or (2) subsequent reversal sessions relative to the respective control offspring. Furthermore, the expression of activity related-cytoskeletal-associated protein (Arc), an experience-dependent cortical protein marker known to be up-regulated in response to acquisition of a novel behavior, was greater in B(a)P-exposed offspring included in the spatial discrimination cohort versus home cage controls. Collectively, these findings support the hypothesis that in utero exposure to B(a)P during critical windows of development representing peak periods of neurogenesis results in behavioral deficits in later life. PMID:26420751

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model.

PubMed

Enright, Heather A; Falso, Miranda J S; Malfatti, Michael A; Lao, Victoria; Kuhn, Edward A; Hum, Nicholas; Shi, Yilan; Sales, Ana Paula; Haack, Kurt W; Kulp, Kristen S; Buchholz, Bruce A; Loots, Gabriela G; Bench, Graham; Turteltaub, Kenneth W

2017-01-01

Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

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

Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring.

PubMed

Zhang, Tianliang; Zheng, Xinrui; Wang, Xia; Zhao, Hui; Wang, Tingting; Zhang, Hongxia; Li, Wanwei; Shen, Hua; Yu, Li

2018-01-16

Air pollution is a serious environmental health problem closely related to the occurrence of central nervous system diseases. Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM 2.5 ) during pregnancy may affect the growth and development of infants. The present study was to investigate the effects of maternal exposure to PM 2.5 during pregnancy on brain development in mice offspring. Pregnant mice were randomly divided into experimental groups of low-, medium-, or high-dosages of PM 2.5 , a mock-treated group which was treated with the same amount of phosphate buffer solution (PBS), and acontrol group which was untreated. The ethology of offspring mice on postnatal days 1, 7, 14, 21, and 30, along with neuronal development and apoptosis in the cerebral cortex were investigated. Compared with the control, neuronal mitochondrial cristae fracture, changed autophagy characteristics, significantly increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cell rate, and mRNA levels of apoptosis-related caspase-8 and caspase-9 were found in cerebral cortex of mice offspring from the treatment groups, with mRNA levels of Bcl-2 and ratio of Bcl-2 to Bax decreased. Treatment groups also demonstrated enhanced protein expressions of apoptosis-related cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, along with declined proliferating cell nuclear antigen (PCNA), Bcl-2, and ratio of Bcl-2 to Bax. Open field experiments and tail suspension experiments showed that exposure to high dosage of PM 2.5 resulted in decreased spontaneous activities but increased static accumulation time in mice offspring, indicating anxiety, depression, and social behavioral changes. Our results suggested that maternal exposure to PM 2.5 during pregnancy might interfere with cerebral cortex development in mice offspring by affecting cell apoptosis.

Transgenerational effects of parent and grandparent gender on offspring development in a biparental beetle species.

PubMed

Lock, Judith E

2012-06-23

Parental effects on offspring life-history traits are common and increasingly well-studied. However, the extent to which these effects persist into offspring in subsequent generations has received less attention. In this experiment, maternal and paternal effects on offspring and grand-offspring were investigated in the biparental burying beetle Nicrophorus vespilloides, using a split-family design. This allowed the separation of prenatal and postnatal transgenerational effects. Grandparent and parent gender were found to have a cumulative effect on offspring development and may provide a selection pressure on the division of parental investment in biparental species.

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

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

Ronco, Ana Maria, E-mail: amronco@inta.cl; Montenegro, Marcela; Castillo, Paula

2011-03-01

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

The effect of pre-laying maternal immunization on offspring growth and immunity differs across experimentally altered postnatal rearing conditions in a wild songbird.

PubMed

Martyka, Rafał; Śliwińska, Ewa B; Martyka, Mirosław; Cichoń, Mariusz; Tryjanowski, Piotr

2018-01-01

Prenatal antibody transfer is an immune-mediated maternal effect by which females can shape postnatal offspring resistance to pathogens and parasites. Maternal antibodies passed on to offspring provide primary protection to neonates against diverse pathogenic antigens, but they may also affect offspring growth and influence the development of an offspring's own immune response. The effects of maternal antibodies on offspring performance commonly require that the disease environment experienced by a mother prior to breeding matches the environment encountered by her offspring after hatching/birth. However, other circumstances, like postnatal rearing conditions that affect offspring food availability, may also determine the effects of maternal antibodies on offspring growth and immunity. To date, knowledge about how prenatal immune-mediated maternal effects interact with various postnatal rearing conditions to affect offspring development and phenotype in wild bird population remains elusive. Here we experimentally studied the interactive effects of pre-laying maternal immunization with a bacterial antigen (lipopolysaccharide) and post-hatching rearing conditions, altered by brood size manipulation, on offspring growth and humoral immunity of wild great tits ( Parus major ). We found that maternal immunization and brood size manipulation interactively affected the growth and specific humoral immune response of avian offspring. Among nestlings reared in enlarged broods, only those that originated from immunized mothers grew better and were heavier at fledging stage compared to those that originated from non-immunized mothers. In contrast, no such effects were observed among nestlings reared in non-manipulated (control) broods. Moreover, offspring of immunized females had a stronger humoral immune response to lipopolysaccharide during postnatal development than offspring of non-immunized females, but only when the nestling was reared in control broods. This study demonstrates that offspring development and their ability to cope with pathogens after hatching are driven by mutual influences of pathogen-induced prenatal maternal effects and post-hatching rearing conditions. Our findings suggest that immune-mediated maternal effects may have context-dependent influences on offspring growth and immune function, related to the postnatal environmental conditions experienced by the progeny.

A Gestational High Protein Diet Affects the Abundance of Muscle Transcripts Related to Cell Cycle Regulation throughout Development in Porcine Progeny

PubMed Central

Oster, Michael; Murani, Eduard; Metges, Cornelia C.; Ponsuksili, Siriluck; Wimmers, Klaus

2012-01-01

Background In various animal models pregnancy diets have been shown to affect offspring phenotype. Indeed, the underlying programming of development is associated with modulations in birth weight, body composition, and continual diet-dependent modifications of offspring metabolism until adulthood, producing the hypothesis that the offspring's transcriptome is permanently altered depending on maternal diet. Methodology/Principal Findings To assess alterations of the offspring's transcriptome due to gestational protein supply, German Landrace sows were fed isoenergetic diets containing protein levels of either 30% (high protein - HP) or 12% (adequate protein - AP) throughout their pregnancy. Offspring muscle tissue (M. longissimus dorsi) was collected at 94 days post conception (dpc), and 1, 28, and 188 days post natum (dpn) for use with Affymetrix GeneChip Porcine Genome Arrays and subsequent statistical and Ingenuity pathway analyses. Numerous transcripts were found to have altered abundance at 94 dpc and 1 dpn; at 28 dpn no transcripts were altered, and at 188 dpn only a few transcripts showed a different abundance between diet groups. However, when assessing transcriptional changes across developmental time points, marked differences were obvious among the dietary groups. Depending on the gestational dietary exposure, short- and long-term effects were observed for mRNA expression of genes related to cell cycle regulation, energy metabolism, growth factor signaling pathways, and nucleic acid metabolism. In particular, the abundance of transcripts related to cell cycle remained divergent among the groups during development. Conclusion Expression analysis indicates that maternal protein supply induced programming of the offspring's genome; early postnatal compensation of the slight growth retardation obvious at birth in HP piglets resulted, as did a permanently different developmental alteration and responsiveness to the common environment of the transcriptome. The transcriptome modulations are interpreted as the molecular equivalent of developmental plasticity of the offspring that necessitates adaptation and maintenance of the organismal phenotype. PMID:22496824

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.

Fitness consequences of parental compatibility in the frog Crinia georgiana.

PubMed

Dziminski, Martin A; Roberts, J Dale; Simmons, Leigh W

2008-04-01

Theory suggests that multiple mating by females can evolve as a mechanism for acquiring compatible genes that promote offspring fitness. Genetic compatibility models predict that differences in fitness among offspring arise from interactions between male and female haplotypes. Using a cross-classified breeding design and in vitro fertilization, we raised families of maternal and paternal half-siblings of the frog Crinia georgiana, a species with a polyandrous breeding system and external fertilization. After controlling for variation in maternal provisioning, we found significant effects of interacting parental haplotypes on fertilization success, and nonadditive genetic effects on measures of offspring fitness such as embryo survival, and survival to, size at, and time to metamorphosis. Additive genetic variation due to males and females was negligible, and not statistically significant for any of the fitness traits measured. Combinations of parental haplotypes that resulted in high rates of fertilization produced offspring with higher embryo survival and rapid juvenile development. We suggest that a gamete recognition mechanism for selective fertilization by compatible sperm may promote offspring fitness in this system.

Maternal swimming exercise during pregnancy attenuates anxiety/depressive-like behaviors and voluntary morphine consumption in the pubertal male and female rat offspring born from morphine dependent mothers.

PubMed

Torabi, Masoumeh; Pooriamehr, Alireza; Bigdeli, Imanollah; Miladi-Gorji, Hossein

2017-10-17

This study was designed to examine whether maternal swimming exercise during pregnancy would attenuate prenatally morphine-induced anxiety, depression and voluntary consumption of morphine in the pubertal male and female rat offspring. Pregnant rats during the development of morphine dependence were allowed to swim (30-45min/d, 3days per a week) on gestational days 11-18. Then, the pubertal male and female rat offspring were tested for the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that male and female rat offspring born of the swimmer morphine-dependent mothers exhibited an increase in EPM open arm time and entries, higher levels of sucrose preference than their sedentary control mothers. Voluntary consumption of morphine was less in the male and female rat offspring born of the swimmer morphine-dependent mothers as compared with their sedentary control mothers during three periods of the intake of drug. Thus, swimming exercise in pregnant morphine dependent mothers decreased anxiety, depressive-like behavior and also the voluntary morphine consumption in the pubertal male and female offspring, which may prevent prenatally morphine-induced behavioral sensitization in offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

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

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

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 also had ABR amplitude-intensity profiles suggestive of hyperacusis. These results are consistent with the Barker hypothesis concerning the fetal and neonatal origins of adult diseases. Thus, consuming diets that are excessively rich or deficient in ω-3 FA during pregnancy and lactation seems inadvisable because of risks for long-lasting adverse effects on brain development and sensory function. PMID:18834936

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 highly feed-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production. PMID:29577087

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.

Birth of Healthy Offspring following ICSI in In Vitro-Matured Common Marmoset (Callithrix jacchus) Oocytes

PubMed Central

Takahashi, Tsukasa; Hanazawa, Kisaburo; Inoue, Takashi; Sato, Kenya; Sedohara, Ayako; Okahara, Junko; Suemizu, Hiroshi; Yagihashi, Chie; Yamamoto, Masafumi; Eto, Tomoo; Konno, Yusuke; Okano, Hideyuki; Suematsu, Makoto; Sasaki, Erika

2014-01-01

Intracytoplasmic sperm injection (ICSI), an important method used to treat male subfertility, is applied in the transgenic technology of sperm-mediated gene transfer. However, no study has described successful generation of offspring using ICSI in the common marmoset, a small non-human primate used as a model for biomedical translational research. In this study, we investigated blastocyst development and the subsequent live offspring stages of marmoset oocytes matured in vitro and fertilized by ICSI. To investigate the optimal timing of performing ICSI, corrected immature oocytes were matured in vitro and ICSI was performed at various time points (1–2 h, 2–4 h, 4–6 h, 6–8 h, and 8–10 h after extrusion of the first polar body (PB)). Matured oocytes were then divided randomly into two groups: one was used for in vitro fertilization (IVF) and the other for ICSI. To investigate in vivo development of embryos followed by ICSI, 6-cell- to 8-cell-stage embryos and blastocysts were nonsurgically transferred into recipient marmosets. Although no significant differences were observed in the fertilization rate of blastocysts among ICSI timing after the first PB extrusion, the blastocyst rate at 1–2 h was lowest among groups at 2–4 h, 4–6 h, 6–8 h, and 8–10 h. Comparing ICSI to IVF, the fertilization rates obtained in ICSI were higher than in IVF (p>0.05). No significant difference was noted in the cleaved blastocyst rate between ICSI and IVF. Following the transfer of 37 ICSI blastocysts, 4 of 20 recipients became pregnant, while with the transfer of 21 6-cell- to 8-cell-stage ICSI embryos, 3 of 8 recipients became pregnant. Four healthy offspring were produced and grew normally. These are the first marmoset offspring produced by ICSI, making it an effective fertilization method for marmosets. PMID:24751978

Effects of seven diets on the population dynamics of laboratory cultured Tisbe holothuriae Humes (Copepoda, Harpacticoida)

NASA Astrophysics Data System (ADS)

Miliou, H.; Moraïtou-Apostolopoulou, M.

1991-09-01

The harpacticoid copepod Tisbe holothuriae was collected from Saronicos Gulf (Greece) and reared under constant laboratory conditions. In order to study the effects of food on the population dynamics, seven diets were tested: the seaweed Ulva; five artificial compound feeds: the liquid Fryfood® (Waterlife), a powder of Mytilus, yeast, soya and Spirulina, respectively; and a mixed diet consisting of Ulva and Fryfood. The life cycle parameters (mortality, sex ratio, generation time, offspring production) were measured, and the demographic variables [mean generation time (T), net reproductive rate (Ro), and intrinsic rate of natural increase (rm)] were determined. As to their efficiency regarding population dynamics, the diets ranked as follows: (1) Ulva+Fryfood, (2), Ulva, (3) Fryfood, (4) Mytilus, (5) soya, (6) yeast, and (7) Spirulina. In this order they cause a progressive increase of both larval mortality and generation time, a progressive decrease of sex ratio, number of offspring per egg sac, number of egg sacs per female and, consequently, of Ro and rm. The observed differences between diets were most pronounced with respect to offspring production. Of the compound diets, those containing animal extracts were more efficient than those containing vegetable materials. Ulva plays an important role in the nutrition of T. holothuriae, favouring offspring production as well as larval survival, development and pigmentation. Ulva in combination with Fryfood led to a greater copepodid survival and offspring production. This mixed diet proved to be the most favourable for rearing the Greek population of t. holothuriae, resulting in an efficient intrinsic rate of natural increase (rm=0.304) of the population.

Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

PubMed

Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

2010-03-01

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

Differential effects of prenatal stress on metabolic programming in diet-induced obese and dietary-resistant rats.

PubMed

Balasubramanian, Priya; Varde, Pratibha A; Abdallah, Simon Labib; Najjar, Sonia M; MohanKumar, P S; MohanKumar, Sheba M J

2015-09-15

Stress during pregnancy is a known contributing factor for the development of obesity in the offspring. Since maternal obesity is on the rise, we wanted to identify the effects of prenatal stress in the offspring of diet-induced obese (DIO) rats and compare them with the offspring of dietary-resistant (DR) rats. We hypothesized that prenatal stress would make both DIO and DR offspring susceptible to obesity, but the effect would be more pronounced in DIO rats. Pregnant DIO and DR rats were divided into two groups: nonstressed controls (control) and prenatal stress (subjected to restraint stress, three times/day from days 14 to 21 of gestation). After recording birth weight and weaning weight, male offspring were weaned onto a chow diet for 9 wk and shifted to a high-fat (HF) diet for 1 wk. At the end of the 10th wk the animals were euthanized, and visceral adipose mass, blood glucose, serum insulin, and C-peptide levels were measured. Prenatal stress resulted in hyperinsulinemia and higher C-peptide levels without altering caloric intake, body weight gain, or fat mass in the DIO offspring after 1 wk of HF intake, but not in DR offspring. To determine the mechanism underlying the hyperinsulinemia, we measured the levels of CEACAM1 that are responsible for insulin clearance. CEACAM1 levels in the liver were reduced in prenatally stressed DIO offspring after the HF challenge, suggesting that preexisting genetic predisposition in combination with prenatal stress increases the risk for obesity in adulthood, especially when offspring are fed a HF diet. Copyright © 2015 the American Physiological Society.

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

High food abundance permits the evolution of placentotrophy: evidence from a placental lizard, Pseudemoia entrecasteauxii.

PubMed

Van Dyke, James U; Griffith, Oliver W; Thompson, Michael B

2014-08-01

Mechanisms of reproductive allocation are major determinants of fitness because embryos cannot complete development without receiving sufficient nutrition from their parents. The nourishment of offspring via placentas (placentotrophy) has evolved repeatedly in vertebrates, including multiple times in squamate reptiles (lizards and snakes). Placentotrophy has been suggested to evolve only if food is sufficiently abundant throughout gestation to allow successful embryogenesis. If scarcity of food prevents successful embryogenesis, females should recoup nutrients allocated to embryos via abortion, reabsorption, and/or cannibalism. We tested these hypotheses in the placentotrophic southern grass skink Pseudemoia entrecasteauxii. We fed females one of four diets (high constant, high variable, low constant, and low variable) during gestation and tested the effects of both food amount and schedule of feeding on developmental success, cannibalism rate, placental nutrient transport, offspring size, and maternal growth and body condition. Low food availability reduced developmental success, placental nutrient transport, offspring size, and maternal growth and body condition. Cannibalism of offspring also increased when food was scarce. Schedule of feeding did not affect offspring or mothers. We suggest that high food abundance and ability to abort and cannibalize poor-quality offspring are permissive factors necessary for placentotrophy to be a viable strategy of reproductive allocation.

Programming of maternal and offspring disease: impact of growth restriction, fetal sex and transmission across generations

PubMed Central

Cheong, Jean N.; Moritz, Karen M.; Cuffe, James S. M.

2016-01-01

Abstract Babies born small are at an increased risk of developing myriad adult diseases. While growth restriction increases disease risk in all individuals, often a second hit is required to unmask ‘programmed’ impairments in physiology. Programmed disease outcomes are demonstrated more commonly in male offspring compared with females, with these sex‐specific outcomes partly attributed to different placenta‐regulated growth strategies of the male and female fetus. Pregnancy is known to be a major risk factor for unmasking a number of conditions and can be considered a ‘second hit’ for women who were born small. As such, female offspring often develop impairments of physiology for the first time during pregnancy that present as pregnancy complications. Numerous maternal stressors can further increase the risk of developing a maternal complication during pregnancy. Importantly, these maternal complications can have long‐term consequences for both the mother after pregnancy and the developing fetus. Conditions such as preeclampsia, gestational diabetes and hypertension as well as thyroid, liver and kidney diseases are all conditions that can complicate pregnancy and have long‐term consequences for maternal and offspring health. Babies born to mothers who develop these conditions are often at a greater risk of developing disease in adulthood. This has implications as a mechanism for transmission of disease across generations. In this review, we discuss the evidence surrounding long‐term intergenerational implications of being born small and/or experiencing stress during pregnancy on programming outcomes. PMID:26970222

Trajectories of maternal leisure-time physical activity and sedentary behavior during adolescence to young adulthood and offspring birthweight.

PubMed

Badon, Sylvia E; Littman, Alyson J; Chan, Kwun Chuen Gary; Williams, Michelle A; Enquobahrie, Daniel A

2017-11-01

The objectives of the study were to determine the extent to which trajectories of maternal preconception leisure-time physical activity (LTPA) and leisure-time sedentary behavior (LTSB) during adolescence and young adulthood are associated with offspring birth weight (BW) and to test if these associations differ by offspring sex or maternal pre-pregnancy overweight-obese status. Participants with one or more birth (n = 1408) were identified from the National Longitudinal Study of Adolescent to Adult Health. Group-based trajectory modeling was used to characterize trajectories of LTPA (frequency/week) and LTSB (hours/week) which were measured, on average, over 7 years between age 15 and 22 years. Weighted regression and Wald tests were used to estimate and test mean differences and odds ratios for BW, small for gestational age, and large for gestational age (LGA). Three trajectories were identified for LTPA and five for LTSB. Associations differed by offspring sex for continuous BW and LGA (interaction P = .10 and .008, respectively). Among female offspring, participants with high followed by decreasing LTPA delivered offspring with 90 g greater BW (95% confidence interval [CI]: -4 to 184) and 72% greater risk of LGA (95% CI: 0.94-3.14), compared with participants with low LTPA. Among male offspring, LTPA patterns were not associated with BW. A pattern of high then decreasing LTPA among normal weight, but not overweight-obese women, was associated with 2.03 times greater risk of LGA (95% CI: 1.06-3.88). LTSB trajectories were not associated with BW. Associations of preconception trajectories of LTPA with offspring BW may differ by offspring sex and maternal pre-pregnancy overweight-obese status. Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

PubMed

Pallarés, María Eugenia; Adrover, Ezequiela; Baier, Carlos Javier; Bourguignon, Nadia S; Monteleone, Melisa C; Brocco, Marcela A; González-Calvar, Silvia I; Antonelli, Marta C

2013-07-01

Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.

Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies.

PubMed

Rasic, Daniel; Hajek, Tomas; Alda, Martin; Uher, Rudolf

2014-01-01

Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%-42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08-3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57-5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48-2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02-2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20-18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19-15.16, P = .631). Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.

Multiple host-plant use may arise from gender-specific fitness effects

PubMed Central

Gibbs, Melanie; Lace, Lesley A.; Jones, Martin J.; Moore, Allen J.

2006-01-01

Ovipositing females are predicted to select host-plants that will maximise offspring survival and fitness. Yet hosts often differ in the component of larval fitness affected so host-selection often involves a trade-off between short development times and large size and high fecundity of offspring. If host-species can directly affect development rates and body size, and if there are gender differences in resource allocation during development, there can be different sex-specific selection pressures associated with different hosts. Using a Madeiran population of the speckled wood butterfly Pararge aegeria (L.) as the model species gender differences in larval development and size were examined in response to the hosts Brachypodium sylvaticum, Holcus lanatus and Poa annua. It was observed that male and female P. aegeria larvae differed, with their responses dependent on the host species. These results would suggest that oviposition behavior is a complex process, and use of multiple hosts may have evolved to balance the conflicting needs of male and female larvae. Co-evolution of host selection and oviposition behaviors may help to balance the differing performance needs of offspring. PMID:19537967

Multigenerational hybridisation and its consequences for maternal effects in Atlantic salmon

PubMed Central

Debes, P V; Fraser, D J; McBride, M C; Hutchings, J A

2013-01-01

Outbreeding between segregating populations can be important from an evolutionary, conservation and economical-agricultural perspective. Whether and how outbreeding influences maternal effects in wild populations has rarely been studied, despite both the prominent maternal influence on early offspring survival and the known presence of fitness effects resulting from outbreeding in many taxa. We studied several traits during the yolk-feeding stage in multigenerational crosses between a wild and a domesticated Atlantic salmon (Salmo salar) population up to their third-generation hybrid in a common laboratory environment. Using cross-means analysis, we inferred that maternal additive outbreeding effects underlie most offspring traits but that yolk mass also underlies maternal dominant effects. As a consequence of the interplay between additive and dominant maternally controlled traits, offspring from first-generation hybrid mothers expressed an excessive proportion of residual yolk mass, relative to total mass, at the time of first feeding. Their residual yolk mass was 23–97% greater than those of other crosses and 31% more than that predicted by a purely additive model. Offspring additive, epistatic and epistatic offspring-by-maternal outbreeding effects appeared to further modify this largely maternally controlled cross-means pattern, resulting in an increase in offspring size with the percentage of domesticated alleles. Fitness implications remain elusive because of unknown phenotype-by-environment interactions. However, these results suggest how mechanistically co-adapted genetic maternal control on early offspring development can be disrupted by the effects of combining alleles from divergent populations. Complex outbreeding effects at both the maternal and offspring levels make the prediction of hybrid phenotypes difficult. PMID:23652564

Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice.

PubMed

Bouchaud, G; Castan, L; Chesné, J; Braza, F; Aubert, P; Neunlist, M; Magnan, A; Bodinier, M

2016-01-01

Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breastfeeding structure as a test of parental investment theory in Papua New Guinea.

PubMed

Tracer, David P

2009-01-01

Evolutionary parental investment theory predicts that parents invest preferentially in offspring best able to translate investments into fitness payoffs. It has also been proposed that where the reproductive prospects of offspring are directly correlated with parental investment and variance in fertility is higher for males than females, parents in better condition should bias investment toward males while those in poorer condition should bias investment toward females. Lactation is arguably among the costliest forms of investment expended by mothers and is thus expected to be allocated in ways consistent with fitness payoffs. Quantitative data collected among 110 Papua New Guinean mother-infant pairs during 470 h of focal follows on nursing frequency and duration and responses to infant demands by maternal and offspring characteristics are presented to provide empirically-based descriptions of infant care and tests of evolutionary parental investment theory. Results indicate that mothers show very high levels of investment in offspring. However, although breastfeeding in developing countries is often characterized as on-demand, fussing and crying by infants were only attended to with breastfeeding about 30% of the time. Contrary to expectations of parental investment theory that parents should invest less in poorer quality offspring, mothers increased investment in offspring in poorer condition. The expectation that mothers in better condition would bias investment toward male offspring was also not supported; better nourished mothers biased investment toward female offspring. This study illustrates how infant feeding data may be used for testing larger evolutionary questions such as those derived from parental investment theory.

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

Maternal insulin resistance and transient hyperglycemia impact the metabolic and endocrine phenotypes of offspring

PubMed Central

Kahraman, Sevim; Dirice, Ercument; De Jesus, Dario F.; Hu, Jiang

2014-01-01

Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, glucagon, and active GLP-1 were higher in control pups from LIRKO mothers. Analyses of the endocrine pancreas revealed significantly reduced β-cell area in control offspring of LIRKO mothers shortly after birth. β-Cell proliferation and total islet number were also lower in control offspring of LIRKO mothers during early postnatal days. Together, these data indicate that maternal hyperinsulinemia and the transient hyperglycemia impair endocrine pancreas development in the control offspring and induce multiple metabolic alterations in early postnatal life. The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development. PMID:25249504

Gravity-Loading During Pregnancy and Birth: Effects on Neonatal Outcome

NASA Technical Reports Server (NTRS)

Ronca, April E.; Dahl, Bonnie (Technical Monitor)

1998-01-01

In this presentation, I will describe the effects of increased gravity on mammalian development in rodents, from gestation throughout weaning. The work is based on studies of centrifugation-induced hypergravity-rearing, the fundamentals of which will be described. The key variables include: 1) comparison of first-time (primparous) and experienced (multiparous) rodent mothers; 2) prenatal adaptation to the centrifuge; and 3) application of a modest g-load (1.5-g). The reported findings emphasize pregnancy, labor and birth, maternal care and lactation in the dams, and suckling, growth, development, and weaning in the offspring. Pregnancy success and offspring growth and survival will be discussed.

Maternal Nicotine Exposure During Late Gestation and Lactation Increases Anxiety-Like and Impulsive Decision-Making Behavior in Adolescent Offspring of Rat.

PubMed

Lee, Hyunchan; Chung, Sooyeon; Noh, Jihyun

2016-10-01

Prenatal nicotine exposure over an entire pregnancy has been associated with an increased prevalence of hyperactivity, anxiety-like behavior and depression-like behavior in mature rats. However, the effects of maternal nicotine exposure in late gestation and lactation on the psychology and behavior of adolescent rat offspring are unclear. Thus, we investigated the effect of nicotine exposure during late gestation and lactation on anxiety-like and impulsive decision-making behavior in adolescent offspring of rat. Female rats were orally exposed to nicotine which is within range of plasma level of human chronic smokers during the period of third last period of gestation and lactation. When the offspring were weaned, we observed alterations in the anxiety-like behavior and decision-making ability of adolescent rat offspring using light/dark box test and T-maze delay-based cost-benefit decision-making task. The maternal consumption of nicotine reduced both the time spent in the light compartment and the number of transitions compared to nicotine-free rats. Moreover, such nicotine exposed adolescent offspring rats showed impulsive decision making which chose the instant reward in a decision-making situation. We found that nicotine exposure during late gestation and lactation induces an increase in anxiety-like and impulsive decision-making behavior at this developmental stage. These findings suggest that maternal nicotine-exposed offspring are at an increased risk of developing anxious and impulsive behavior.

Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice.

PubMed

Watkins, Adam J; Sirovica, Slobodan; Stokes, Ben; Isaacs, Mark; Addison, Owen; Martin, Richard A

2017-06-01

Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development is largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model

DOE PAGES

Enright, Heather A.; Falso, Miranda J. S.; Malfatti, Michael A.; ...

2017-08-09

Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here in this paper, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantifymore » 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.« less

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model

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

Enright, Heather A.; Falso, Miranda J. S.; Malfatti, Michael A.

Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here in this paper, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantifymore » 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.« less

Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.

PubMed

McKee, Sarah E; Grissom, Nicola M; Herdt, Christopher T; Reyes, Teresa M

2017-06-01

During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life-particularly within the prefrontal cortex (PFC), a brain region critical for executive function-we examined whether early life methyl donor supplementation ( e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.-McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams. © FASEB.

Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet–fed dams

PubMed Central

McKee, Sarah E.; Grissom, Nicola M.; Herdt, Christopher T.; Reyes, Teresa M.

2017-01-01

During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)–fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life—particularly within the prefrontal cortex (PFC), a brain region critical for executive function—we examined whether early life methyl donor supplementation (e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.—McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet–fed dams. PMID:28209774

Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

PubMed

Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

2016-01-01

The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Development and behavior of wild infant-juvenile East Bornean orangutans (Pongo pygmaeus morio) in Danum Valley.

PubMed

Mendonça, Renata S; Kanamori, Tomoko; Kuze, Noko; Hayashi, Misato; Bernard, Henry; Matsuzawa, Tetsuro

2017-01-01

Orangutans have a long period of immaturity and the longest inter-birth interval (IBI) of all mammals, which can be explained by their solitary life style, preventing the mother from rearing two offspring simultaneously (solitary life hypothesis) [corrected]. We collected data on mother-offspring dyads living in a primary lowland forest in Danum Valley, East Borneo in an effort to examine the developmental and behavioral patterns of the subspecies Pongo pygmaeus morio. We analyzed developmental changes in mother-offspring distance, contact, and activity budgets in orangutans ranging from 1 to 7 years of age. The results indicated decreased resting and playing with increasing age, whereas feeding, traveling and social play all increased significantly. Mothers' feeding and traveling time were good predictors of their offspring's feeding and traveling activities. Mother-offspring contact lasted longer in resting contexts; contact during traveling was almost non-existent after 4 years of age. Comparisons with previously published data on the Sumatran species Pongo abelli revealed no fundamental differences in these behavioral measures. However, a shorter association time with the mother after behavioral independence is documented for this East Bornean population in comparison to Sumatran populations. These results are best explained by the solitary life hypothesis, in agreement with previous studies. We suggest that environmental constraints in Bornean forests, as well as a lower population density, should be considered when interpreting the differences between Sumatran and Bornean orangutans in both the period of association with mother and the IBI.

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

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

PubMed

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

2009-09-01

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

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 Elsevier Inc. All rights reserved.

Prenatal ethanol enhances rotational behavior to apomorphine in the 24-month-old rat offspring with small striatal lesion.

PubMed

Gomide, Vânia C; Chadi, Gerson

2004-01-01

Pregnant Wistar rats received a hyperproteic liquid diet containing 37.5% ethanol-derived calories during gestation. Isocaloric amount of liquid diet, with maltose-dextrin substituted for ethanol, was given to control pair-fed dams. Offsprings were allowed to survive until 24 months of age. A set of aged female offsprings of both control diet and ethanol diet groups was registered for spontaneous motor activity, by means of an infrared motion sensor activity monitor, or for apomorphine-induced rotational behavior, while another lot of male offsprings was submitted to an unilateral striatal small mechanical lesion by a needle, 6 days before rotational recordings. Prenatal ethanol did not alter spontaneous motor parameters like resting time as well as the events of small and large movements in the aged offsprings. Bilateral circling behavior was already increased 5 min after apomorphine in the unlesioned offsprings of both the control and ethanol diet groups. However, it lasted more elevated for 45- to 75-min time intervals in the gestational ethanol-exposed offsprings, while decreasing faster in the control offsprings. Apomorphine triggered a strong and sustained elevation of contraversive turns in the striatal-lesioned 24-month-old offsprings of the ethanol group, but only a small and transient elevation was seen in the offsprings of the control diet group. Astroglial and microglial reactions were seen surrounding the striatal needle track lesion. Microdensitometric image analysis demonstrated no differences in the levels of tyrosine hydroxylase immunoreactivity in the striatum of 24-month-old unlesioned and lesioned offsprings of control and alcohol diet groups. The results suggest that ethanol exposure during gestation may alter the sensitivity of dopamine receptor in aged offsprings, which is augmented by even a small striatal lesion.

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

PubMed Central

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

2015-01-01

Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. Key points Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet-induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational weight gain, glucose intolerance, hyperinsulinaemia and mild hyperglycaemia. Compared to the offspring of lean dams, exposure to gestational diabetes mellitus during the prenatal period resulted in obesity, hepatic steatosis and insulin resistance in young rat offspring that consumed a postnatal diet that was low in fat. The combination of maternal gestational diabetes mellitus and the postnatal consumption of a high-fat diet by the offspring caused a more severe metabolic phenotype. Metabolomic profiling of the liver tissues of the offspring of gestational diabetic dams revealed accumulation of lipotoxic lipids and reduced phosphatidylethanolamine levels compared to the offspring of lean dams. The results establish that gestational diabetes mellitus is a driver of hepatic steatosis and insulin resistance in the offspring. PMID:25922055

Effects of prenatal and perinatal administration of phencyclidine on the behavioral development of rat offspring.

PubMed

Nabeshima, T; Yamaguchi, K; Hiramatsu, M; Ishikawa, K; Furukawa, H; Kameyama, T

1987-11-01

The effects of prenatal and perinatal administration of a nonteratogenic dose of phencyclidine (PCP) on the behavioral development of Sprague-Dawley rats were examined. In the offspring prenatally treated with PCP (10 mg/kg) between days 7 and 17 of gestation, a decrease in maternal body weight in the gestation period, a decrease in fetal body weight and body length, a decrease in viability of offsprings, and a decrease in the body weights of the offspring in the nursing period were observed. Furthermore, PCP pups had difficulty performing the rota-rod task at 4 weeks and exhibited a decrease in sensitivity to challenged PCP at 5 weeks (female). In the offspring prenatally treated with PCP between days 7 and 21 of gestation, a decrease in the body weights of dams, fetuses and offspring, and a decrease in the viability of offsprings were observed. PCP pups showed an increase in the score for head-twitch response (male), a delay in the development of ambulation, negative geotaxis (male), bar holding and rope-descending behavior (female). However, the PCP administration during prenatal (between days 17 and 21 of gestation) and nursing periods showed only a decrease in viability and body weight of offspring, and a delay in the development of the separation of eyelids. These results suggest that more attention should be given to the developmental toxicity of PCP.

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.

What is the role of mothers in the acquisition of termite-fishing behaviors in wild chimpanzees (Pan troglodytes schweinfurthii)?

PubMed

Lonsdorf, Elizabeth V

2006-01-01

This paper explores the role of maternal influences on the acquisition of a tool-using task in wild chimpanzees (Pan troglodytes schweinfurthii) in order to build on and complement previous work done in captivity. Young chimpanzees show a long period of offspring dependency on mothers and it is during this period that offspring learn several important skills, especially how to and on what to forage. At Gombe National Park, one skill that is acquired during dependency is termite-fishing, a complex behavior that involves inserting a tool made from the surrounding vegetation into a termite mound and extracting the termites that attack and cling to the tool. All chimpanzees observed at Gombe have acquired the termite-fishing skill by the age of 5.5 years. Since the mother is the primary source of information throughout this time period, I investigated the influence of mothers' individual termite-fishing characteristics on their offsprings' speed of acquisition and proficiency at the skill once acquired. Mother's time spent alone or with maternal family members, which is highly correlated to time spent termite-fishing, was positively correlated to offspring's acquisition of critical elements of the skill. I also investigated the specific types of social interactions that occur between mothers and offspring at the termite mound and found that mothers are highly tolerant to offspring, even when the behavior of the offspring may disrupt the termite-fishing attempt. However, no active facilitation by mothers of offsprings' attempts were observed.

Testing models of parental investment strategy and offspring size in ants.

PubMed

Gilboa, Smadar; Nonacs, Peter

2006-01-01

Parental investment strategies can be fixed or flexible. A fixed strategy predicts making all offspring a single 'optimal' size. Dynamic models predict flexible strategies with more than one optimal size of offspring. Patterns in the distribution of offspring sizes may thus reveal the investment strategy. Static strategies should produce normal distributions. Dynamic strategies should often result in non-normal distributions. Furthermore, variance in morphological traits should be positively correlated with the length of developmental time the traits are exposed to environmental influences. Finally, the type of deviation from normality (i.e., skewed left or right, or platykurtic) should be correlated with the average offspring size. To test the latter prediction, we used simulations to detect significant departures from normality and categorize distribution types. Data from three species of ants strongly support the predicted patterns for dynamic parental investment. Offspring size distributions are often significantly non-normal. Traits fixed earlier in development, such as head width, are less variable than final body weight. The type of distribution observed correlates with mean female dry weight. The overall support for a dynamic parental investment model has implications for life history theory. Predicted conflicts over parental effort, sex investment ratios, and reproductive skew in cooperative breeders follow from assumptions of static parental investment strategies and omnipresent resource limitations. By contrast, with flexible investment strategies such conflicts can be either absent or maladaptive.

A longitudinal high-risk study of adolescent anxiety, depression and parent-severity on the developmental course of risk-adjustment.

PubMed

Rawal, Adhip; Riglin, Lucy; Ng-Knight, Terry; Collishaw, Stephan; Thapar, Anita; Rice, Frances

2014-11-01

Adolescence is associated with developments in the reward system and increased rates of emotional disorders. Familial risk for depression may be associated with disruptions in the reward system. However, it is unclear how symptoms of depression and anxiety influence the development of reward-processing over adolescence and whether variation in the severity of parental depression is associated with hyposensitivity to reward in a high-risk sample. We focused on risk-adjustment (adjusting decisions about reward according to the probability of obtaining reward) as this was hypothesized to improve over adolescence. In a one-year longitudinal sample (N = 197) of adolescent offspring of depressed parents, we examined how symptoms of depression and anxiety (generalized anxiety and social anxiety) influenced the development of risk-adjustment. We also examined how parental depression severity influenced adolescent risk-adjustment. Risk-adjustment improved over the course of the study indicating improved adjustment of reward-seeking to shifting contingencies. Depressive symptoms were associated with decreases in risk-adjustment over time while social anxiety symptoms were associated with increases in risk-adjustment over time. Specifically, depression was associated with reductions in reward-seeking at favourable reward probabilities only, whereas social anxiety (but not generalized anxiety) led to reductions in reward-seeking at low reward probabilities only. Parent depression severity was associated with lowered risk-adjustment in offspring and also influenced the longitudinal relationship between risk-adjustment and offspring depression. Anxiety and depression distinctly alter the pattern of longitudinal change in reward-processing. Severity of parent depression was associated with alterations in adolescent offspring reward-processing in a high-risk sample. © 2014 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Maternal Patterns of Marijuana Use and Early Sexual Behavior in Offspring of Teenage Mothers

PubMed Central

Goldschmidt, Lidush; Cornelius, Marie D.

2015-01-01

Teenage mothers use marijuana more frequently than older mothers, and marijuana use may predict HIV risk behavior in offspring. Our goals were to (1) describe trajectories of marijuana use in teenage mothers and (2) determine if these trajectories were associated with early sexual behavior in their offspring. Pregnant adolescents (12–18 years) were recruited at a prenatal clinic and interviewed during pregnancy, at delivery, and during follow-up visits when offspring were 6, 10, 14 and 16 years old. At 16 years, 332 women (71 % Black, 29 % White) and their offspring were assessed. Mothers were asked about their marijuana use at each time point. Offspring reported on their sexual behavior at age 14. Trajectory analyses using growth mixture models revealed four maternal patterns of marijuana use: no use, only at the 6 year follow-up, quit by the 16 year follow-up, and used across most of the time points. The children of chronic users were more likely to have early sex. The maternal marijuana trajectory group variable remained a statistically significant predictor in multivariate models controlling for race, gender, socioeconomic status, child pubertal timing, child externalizing behavior problems, and child marijuana use. These findings suggest that a minority of teenage mothers continue to use marijuana over time. Chronic maternal marijuana use across a decade was associated with early sex in offspring (oral or vaginal sex by age 14). Early sexual behavior places these children at significantly higher risk of teenage pregnancy and HIV risk behaviors. PMID:24942139

Transient habitats limit development time for periodical cicadas.

PubMed

Karban, Richard

2014-01-01

Periodical cicadas (Magicicada spp.) mature in 13 or 17 years, the longest development times for any non-diapausing insects. Selection may favor prolonged development since nymphs experience little mortality and individuals taking 17 years have been shown to have greater fecundity than those taking 13 years. Why don't periodical cicadas take even longer to develop? Nymphs feed on root xylem fluid and move little. Ovipositing females prefer fast-growing trees at forest edges. I hypothesized that (1) adults emerging at edges would be heavier than those from forest interiors and (2) habitat changes could limit development time. I collected newly eclosed females that had neither fed as adults nor moved from their site of development. For M. septendecim, females from edges were 4.9% heavier than those from the interior. I assumed that emergence density indicated habitat quality and measured density at eight sites in 1979, 1996, and 2013. Over three generations, variation in densities was great; densities at two sites crashed, and at one site they exploded to 579/m2 Habitat transience may limit development time because only adults can reassess habitats and reposition offspring. In conclusion, cicadas are affected by habitat characteristics, habitats change over 17 years, and cicadas may emerge, mate, and redistribute their offspring to track habitat dynamics.

Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

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

Maiellaro, Marília; Correa-Costa, Matheus; Vitoretti, Luana Beatriz

Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillatedmore » water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment.« less

Associations of Maternal Light/Moderate Leisure-Time Walking and Yoga With Offspring Birth Size.

PubMed

Badon, Sylvia E; Littman, Alyson J; Chan, K C Gary; Williams, Michelle A; Enquobahrie, Daniel A

2018-06-01

Although perinatal walking and yoga have been associated with decreased risks of pregnancy complications, associations with offspring birth size have been inconsistent. We investigated associations of prepregnancy and early pregnancy leisure-time light/moderate walking and yoga practice with birth size. Study participants (N = 3687) reported leisure-time physical activity duration (hours per week) in the year before pregnancy and early pregnancy. Birth size was abstracted from medical records. Regression was used to determine mean differences in birth weight, head circumference, and ponderal index. Interaction terms were used to assess effect modification by offspring sex. About one-third of women reported light/moderate leisure-time walking and about 10% reported yoga practice. Women in the highest tertile for prepregnancy (mean: 2.9 h/wk; range: 1.4-20 h/wk) or early pregnancy (mean: 5.9 h/wk; range: 3.1-24 h/wk) light/moderate walking had offspring with 0.9 and 1.5 kg/m 3 greater ponderal index (95% confidence interval, 0.3 to 1.4 and 0.7 to 2.4, respectively) compared with women who reported no light/moderate walking in the same time period. Light/moderate walking was not associated with birth weight or head circumference. Yoga practice was not associated with birth size. Associations were similar by offspring sex. Light/moderate leisure-time walking may be associated with greater offspring ponderal index.

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.

Maternal high-fat diet and obesity impact palatable food intake and dopamine signaling in nonhuman primate offspring.

PubMed

Rivera, Heidi M; Kievit, Paul; Kirigiti, Melissa A; Bauman, Leigh Ann; Baquero, Karalee; Blundell, Peter; Dean, Tyler A; Valleau, Jeanette C; Takahashi, Diana L; Frazee, Tim; Douville, Luke; Majer, Jordan; Smith, M Susan; Grove, Kevin L; Sullivan, Elinor L

2015-11-01

To utilize a nonhuman primate model to examine the impact of maternal high-fat diet (HFD) consumption and pre-pregnancy obesity on offspring intake of palatable food and to examine whether maternal HFD consumption impaired development of the dopamine system, critical for the regulation of hedonic feeding. The impact of exposure to maternal HFD and obesity on offspring consumption of diets of varying composition was assessed after weaning. The influence of maternal HFD consumption on the development of the prefrontal cortex-dopaminergic system at 13 months of age was also examined. During a preference test, offspring exposed to maternal HFD consumption and obesity displayed increased intake of food high in fat and sugar content relative to offspring from lean control mothers. Maternal HFD consumption suppressed offspring dopamine signaling (as assessed by immunohistochemistry) relative to control offspring. Specifically, there was decreased abundance of dopamine fibers and of dopamine receptor 1 and 2 proteins. This study reveals that offspring exposed to both maternal HFD consumption and maternal obesity during early development are at increased risk for obesity due to overconsumption of palatable energy-dense food, a behavior that may be related to reduced central dopamine signaling. © 2015 The Obesity Society.

Maternal High-Fat Diet and Obesity Impact Palatable Food Intake and Dopamine Signaling in Nonhuman Primate Offspring

PubMed Central

Rivera, Heidi M.; Kievit, Paul; Kirigiti, Melissa A.; Bauman, Leigh Ann; Baquero, Karalee; Blundell, Peter; Dean, Tyler A.; Valleau, Jeanette C.; Takahashi, Diana L.; Frazee, Tim; Douville, Luke; Majer, Jordan; Smith, M. Susan; Grove, Kevin L.; Sullivan, Elinor L.

2015-01-01

Objective To utilize a nonhuman primate model to examine the impact of maternal high-fat diet (HFD) consumption and pre-pregnancy obesity on offspring intake of palatable food. We will also examine whether maternal HFD consumption impaired development of the dopamine system, critical for the regulation of hedonic feeding. Methods The impact of exposure to maternal HFD and obesity on offspring consumption of diets of varying composition was assessed after weaning. We also examined the influence of maternal HFD consumption on the development of the prefrontal cortex-dopamine system at 13 months of age. Results During a preference test, offspring exposed to maternal obesity and HFD consumption displayed increased intake of food high in fat and sugar content relative to offspring from lean control mothers. Maternal HFD consumption suppressed offspring dopamine signaling (as assessed by immunohistochemistry) relative to control offspring. Specifically, there was decreased abundance of dopamine fibers and of dopamine receptor 1 and 2 protein. Conclusion Our findings reveal that offspring exposed to both maternal HFD consumption and maternal obesity during early development are at increased risk for obesity due to overconsumption of palatable energy-dense food, a behavior that may be related to reduced central dopamine signaling. PMID:26530932

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

PubMed

Lanham, S A; Cagampang, F R; Oreffo, R O C

2014-12-01

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Maternal Bonding through Pregnancy and Postnatal: Findings from an Australian Longitudinal Study.

PubMed

Rossen, Larissa; Hutchinson, Delyse; Wilson, Judy; Burns, Lucinda; Allsop, Steve; Elliott, Elizabeth J; Jacobs, Sue; Macdonald, Jacqui A; Olsson, Craig; Mattick, Richard P

2017-07-01

Background  Mother-infant bonding provides the foundation for secure attachment through the lifespan and organizes many facets of infant social-emotional development, including later parenting. Aims  To describe maternal bonding to offspring across the pregnancy and postnatal periods, and to examine a broad range of sociodemographic and psychosocial predictors of the maternal-offspring bond. Methods  Data were drawn from a sample of 372 pregnant women participating in an Australian population-based longitudinal study of postnatal health and development. Participants completed maternal bonding questionnaires at each trimester and 8 weeks postnatal. Data were collected on a range of sociodemographic and psychosocial factors. Results  Bonding increased significantly through pregnancy, in quality and intensity. Regression analyses indicated that stronger antenatal bonding at all time points (trimesters 1 through 3) predicted stronger postnatal bonding. Older maternal age, birth mother being born in a non-English speaking country, mother not working full time, being a first-time mother, breast-feeding problems, and baby's crying behavior all predicted poorer bonding at 8 weeks postpartum. Conclusion  These novel findings have important implications for pregnant women and their infant offspring, and for health care professionals working in perinatal services. Importantly, interventions to strengthen maternal-fetal bonding would be beneficial during pregnancy to enhance postnatal bonding and infant health outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The association between teenage motherhood and poor offspring outcomes: A national cohort study across 30 years

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage motherhood is associated with poor offspring outcomes but these associations may be influenced by offspring birth year because of substantial social changes in recent decades. Existing research also has not examined whether these associations are due to the specific effect of mother’s age at childbirth or factors shared by siblings in a family. We used a population-based cohort study in Sweden comprising all children born from 1960–1989 (N=3,162,239), and a subsample of siblings differentially exposed to maternal teenage childbearing (N=485,259) to address these limitations. We examined the effect of teenage childbearing on offspring violent and nonviolent criminal convictions, poor academic performance, and substance-related problems. Population-wide, teenage childbearing was associated with offspring criminal convictions, poor academic performance, and substance-related problems. The magnitude of these associations increased over time. Comparisons of differentially exposed siblings indicated no within-family association between teenage childbearing and offspring violent and nonviolent criminal convictions or poor academic performance, although offspring born to teenage mothers were more likely to experience substance-related problems than their later-born siblings. Being born to a teenage mother in Sweden has become increasingly associated with negative outcomes across time, but the nature of this association may differ by outcome. Teenage childbearing may be associated with offspring violent and nonviolent criminal convictions and poor academic performance because of shared familial risk factors but may be causally associated with offspring substance-related problems. The findings suggest that interventions to improve offspring outcomes should delay teenage childbearing and target risk factors influencing all offspring of teenage mothers. PMID:23632141

Rapid onset of maternal vocal recognition in a colonially breeding mammal, the Australian sea lion.

PubMed

Pitcher, Benjamin J; Harcourt, Robert G; Charrier, Isabelle

2010-08-13

In many gregarious mammals, mothers and offspring have developed the abilities to recognise each other using acoustic signals. Such capacity may develop at different rates after birth/parturition, varying between species and between the participants, i.e., mothers and young. Differences in selective pressures between species, and between mothers and offspring, are likely to drive the timing of the onset of mother-young recognition. We tested the ability of Australian sea lion mothers to identify their offspring by vocalisation, and examined the onset of this behaviour in these females. We hypothesise that a rapid onset of recognition may reflect an adaptation to a colonial lifestyle. In a playback study maternal responses to own pup and non-filial vocalisations were compared at 12, 24 and every subsequent 24 hours until the females' first departure post-partum. Mothers showed a clear ability to recognise their pup's voice by 48 hours of age. At 24 hours mothers called more, at 48 hours they called sooner and at 72 hours they looked sooner in response to their own pup's vocalisations compared to those of non-filial pups. We demonstrate that Australian sea lion females can vocally identify offspring within two days of birth and before mothers leave to forage post-partum. We suggest that this rapid onset is a result of selection pressures imposed by a colonial lifestyle and may be seen in other colonial vertebrates. This is the first demonstration of the timing of the onset of maternal vocal recognition in a pinniped species.

Intergenerational transfer of time and risk preferences

PubMed Central

Brown, Heather; van der Pol, Marjon

2015-01-01

There is a growing interest in individual time and risk preferences. Little is known about how these preferences are formed. It is hypothesised that parents may transmit their preferences to their offspring. This paper examines the correlation in offspring and parental time and risk preferences using data from an annual household survey in Australia (the HILDA survey). Both time and risk preferences are examined and we explored whether the correlation in time and risk preferences varies across the distribution of preferences and across the across the four parent–child dyads (mother/daughter, mother/son, father/daughter, father/son). The results show that there is a significant relationship between parents and their young adult offspring risk and time preference measures. The correlation varies across the distribution of time preferences. The correlation was largest for longer planning horizons. Risk averse parents are more likely to have risk averse children. Except for the father/daughter dyad risk seeking parents are more likely to have risk seeking offspring. Some gender differences were found. The association in parental and offspring time preference was larger for mothers than fathers. Daughters are more likely to be influenced by their mother’s risk preferences, however, sons are equally influenced by both parents. The results of this study suggest that the transmission in preferences is more nuanced than previously thought and parental gender may be important. PMID:26412913

Sex and age-dependent effects of a maternal junk food diet on the mu-opioid receptor in rat offspring.

PubMed

Gugusheff, Jessica R; Bae, Sung Eun; Rao, Alexandra; Clarke, Iain J; Poston, Lucilla; Taylor, Paul D; Coen, Clive W; Muhlhausler, Beverly S

2016-03-15

Perinatal junk food exposure increases the preference for palatable diets in juvenile and adult rat offspring. Previous studies have implicated reduced sensitivity of the opioid pathway in the programming of food preferences; however it is not known when during development these changes in opioid signalling first emerge. This study aimed to determine the impact of a maternal junk food (JF) diet on mu-opioid receptor (MuR) expression and ligand binding in two key regions of the reward pathway, the nucleus accumbens (NAc) and the ventral tegmental area (VTA) in rats during the early suckling (postnatal day (PND) 1 and 7) and late suckling/early post-weaning (PND 21 and 28) periods. Female rats were fed either a JF or a control diet for two weeks prior to mating and throughout pregnancy and lactation. MuR expression in the VTA was significantly reduced in female JF offspring on PND 21 and 28 (by 32% and 57% respectively, P<0.05), but not at earlier time points (PND 1 and 7). MuR ligand binding was also reduced (by 22%, P<0.05) in the VTA of female JF offspring on PND 28. No effects of perinatal junk food exposure on MuR mRNA expression or binding were detected at these time points in male offspring. These findings provide evidence that the opioid signalling system is a target of developmental programming by the end of the third postnatal week in females, but not in males. Copyright © 2015 Elsevier B.V. All rights reserved.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel.

PubMed

Dotan, Iris; Alper, Arik; Rachmilewitz, Daniel; Israeli, Eran; Odes, Shmuel; Chermesh, Irit; Naftali, Timna; Fraser, Gerald; Shitrit, Ariella Bar-Gil; Peles, Vardit; Reif, Shimon

2013-08-01

There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development. IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort.

PubMed

Harskamp-van Ginkel, Margreet W; London, Stephanie J; Magnus, Maria C; Gademan, Maaike G; Vrijkotte, Tanja G

2015-01-01

A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7-8 years of life in a large Amsterdam born birth cohort. For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes "ever being diagnosed with asthma" and "wheezing in the past 12 months" on questionnaires. We measured offspring height and weight at age 5-6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma. At the age of 7-8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49-3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28-3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma. Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child's own BMI.

Selective cognitive deficits in adult rats after prenatal exposure to inhaled ethanol.

PubMed

Oshiro, W M; Beasley, T E; McDaniel, K L; Taylor, M M; Evansky, P; Moser, V C; Gilbert, M E; Bushnell, P J

2014-01-01

Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by inhalation, the most likely route of exposure from gasoline-ethanol fuel blends. We evaluated the potential cognitive consequences of ethanol inhalation by exposing pregnant Long Evans rats to clean air or ethanol vapor from gestational days 9-20, a critical period of neuronal development. Concentrations of inhaled ethanol (5000, 10,000, or 21,000 ppm for 6.5h/day) produced modeled peak blood ethanol concentrations (BECs) in exposed dams of 2.3, 6.8, and 192 mg/dL, respectively. In offspring, no dose-related impairments were observed on spatial learning or working memory in the Morris water maze or in operant delayed match-to-position tests. Two measures showed significant effects in female offspring at all ethanol doses: 1) impaired cue learning after trace fear conditioning, and 2) an absence of bias for the correct quadrant after place training during a reference memory probe in the Morris water maze. In choice reaction time tests, male offspring (females were not tested) from the 5000 and 10,000 ppm groups showed a transient increase in decision times. Also, male offspring from the 21,000 ppm group made more anticipatory responses during a preparatory hold period, suggesting a deficit in response inhibition. The increase in anticipatory responding during the choice reaction time test shows that inhaled ethanol yielding a peak BEC of ~200mg/dL can produce lasting effects in the offspring. The lack of a dose-related decrement in the effects observed in females on cue learning and a reference memory probe may reflect confounding influences in the exposed offspring possibly related to maternal care or altered anxiety levels in females. The surprising lack of more pervasive cognitive deficits, as reported by others at BECs in the 200mg/dL range, may reflect route-dependent differences in the kinetics of ethanol. These data show that response inhibition was impaired in the offspring of pregnant rats that inhaled ethanol at concentrations at least 5 orders of magnitude higher than concentrations observed during normal automotive transport and fueling operations, which rarely exceed 100 ppb. Published by Elsevier Inc.

Maternal lung cancer and testicular cancer risk in the offspring.

PubMed

Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

2003-07-01

It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

Not my "type": larval dispersal dimorphisms and bet-hedging in opisthobranch life histories.

PubMed

Krug, Patrick J

2009-06-01

When conditions fluctuate unpredictably, selection may favor bet-hedging strategies that vary offspring characteristics to avoid reproductive wipe-outs in bad seasons. For many marine gastropods, the dispersal potential of offspring reflects both maternal effects (egg size, egg mass properties) and larval traits (development rate, habitat choice). I present data for eight sea slugs in the genus Elysia (Opisthobranchia: Sacoglossa), highlighting potentially adaptive variation in traits like offspring size, timing of metamorphosis, hatching behavior, and settlement response. Elysia zuleicae produced both planktotrophic and lecithotrophic larvae, a true case of poecilogony. Both intracapsular and post-hatching metamorphosis occurred among clutches of "Boselia" marcusi, E. cornigera, and E. crispata, a dispersal dimorphism often misinterpreted as poecilogony. Egg masses of E. tuca hatched for up to 16 days but larvae settled only on the adult host alga Halimeda, whereas most larvae of E. papillosa spontaneously metamorphosed 5-7 days after hatching. Investment in extra-capsular yolk may allow mothers to increase larval size relative to egg size and vary offspring size within and among clutches. Flexible strategies of larval dispersal and offspring provisioning in Elysia spp. may represent adaptations to the patchy habitat of these specialized herbivores, highlighting the evolutionary importance of variation in a range of life-history traits.

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.

Parenting behaviours associated with the development of adaptive and maladaptive offspring personality traits.

PubMed

Johnson, Jeffrey G; Liu, Lydia; Cohen, Patricia

2011-08-01

To investigate the associations of beneficial parenting behaviours with adaptive and maladaptive offspring personality traits that persist into adulthood among individuals in the community. Families (n = 669) participating in the Children in the Community Study were interviewed during the childhood, adolescence, emerging adulthood, and adulthood of the offspring at the mean ages of 6, 14, 16, 22, and 33 years. Twelve types of beneficial maternal and paternal child-rearing behaviour, reported by offspring at the mean age of 16 years, were associated with elevated offspring personality resiliency, at the mean ages of 22 and 33 years, and with low offspring personality disorder trait levels. These longitudinal associations remained significant when histories of childhood behaviour problems and parental psychiatric disorder were controlled statistically. Similar linear (that is, dose-dependent) associations were observed between the number of beneficial parenting behaviours during childhood and adaptive and maladaptive offspring traits at the mean ages of 22 and 33 years. Maternal and paternal behaviours were independently associated with both adaptive and maladaptive offspring traits. Beneficial maternal and paternal child-rearing behaviours may promote the development of adaptive offspring personality traits that endure into adulthood, and they may be prospectively associated with reduced levels of maladaptive offspring traits. These associations may not be attributable to childhood behaviour problems or parental psychiatric disorders, and they may be equally evident during early and middle adulthood.

High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

PubMed

Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

2013-01-01

The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

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

Effects of Perfluorooctanoic Acid on Mouse Mammary Gland Development and Differentiation Resulting from Cross-Foster and Restricted Gestational Exposures

EPA Science Inventory

The adverse consequences of developmental exposures to perfluorooctanoic acid (PFOA) have been established, and include impaired development of the offspring mammary gland (MG). However, the relationship between the timing or route of exposure, and the phenotypic consequences in ...

Near-infrared laser irradiation improves the development of mouse pre-implantation embryos.

PubMed

Yokoo, Masaki; Mori, Miho

2017-05-27

The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing of blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

PubMed

Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

2015-07-17

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

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

Host plant utilization in the comma butterfly: sources of variation and evolutionary implications.

PubMed

Janz, Niklas; Nylin, Sören; Wedell, Nina

1994-09-01

A major challenge in the study of insect-host plant interactions is to understand how the different aspects of offspring performance interact to produce a preference hierarchy in the ovipositing females. In this paper we investigate host plant preference of the polyphagous butterfly Polygonia c-album (Lepidoptera: Nymphalidae) and compare it with several aspects of the life history of its offspring (growth rate, development time, adult size, survival and female fecundity). Females and offspring were tested on four naturally used host plants (Urtica dioica, Ulmus glabra, Salix caprea, and Betula pubescens). There was substantial individual variation in host plant preference, including reversals in rank order, but the differences were largely confined to differences in the ranking of Urtica dioica and S. caprea. Different aspects of performance on these two plants gave conflicting and complementary results, implying a trade-off between short development time on U. dioica, and larger size and higher fecundity on S. caprea. As all performance components showed low individual variation the large variation in host plant preference was interpreted as due to alternative oviposition strategies on the basis of similar 'performance hierarchies'. This indicates that the larval performance component of host-plant utilization may be more conservative to evolutionary change than the preference of ovipositing females. Possible macro-evolutionary implications of this are discussed.

Using Response Surface Analysis to Interpret the Impact of Parent–Offspring Personality Similarity on Adolescent Externalizing Problems

PubMed Central

Laceulle, Odillia M.; Van Aken, Marcel A.G.; Ormel, Johan

2017-01-01

Abstract Personality similarity between parent and offspring has been suggested to play an important role in offspring's development of externalizing problems. Nonetheless, much remains unknown regarding the nature of this association. This study aimed to investigate the effects of parent–offspring similarity at different levels of personality traits, comparing expectations based on evolutionary and goodness‐of‐fit perspectives. Two waves of data from the TRAILS study (N = 1587, 53% girls) were used to study parent–offspring similarity at different levels of personality traits at age 16 predicting externalizing problems at age 19. Polynomial regression analyses and Response Surface Analyses were used to disentangle effects of different levels and combinations of parents and offspring personality similarity. Although several facets of the offspring's personality had an impact on offspring's externalizing problems, few similarity effects were found. Therefore, there is little support for assumptions based on either an evolutionary or a goodness‐of‐fit perspective. Instead, our findings point in the direction that offspring personality, and at similar levels also parent personality might impact the development of externalizing problems during late adolescence. © 2017 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology PMID:28303077

Influence of maternal thyroid hormones during gestation on fetal brain development

PubMed Central

Moog, Nora K.; Entringer, Sonja; Heim, Christine; Wadhwa, Pathik D.; Kathmann, Norbert; Buss, Claudia

2015-01-01

Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention. PMID:26434624

The sperm of aging male bustards retards their offspring's development.

PubMed

Preston, Brian T; Saint Jalme, Michel; Hingrat, Yves; Lacroix, Frederic; Sorci, Gabriele

2015-02-03

Understanding whether the sperm of older males has a diminished capacity to produce successful offspring is a key challenge in evolutionary biology. We investigate this issue using 10 years of reproductive data on captive long-lived houbara bustards (Chlamydotis undulata), where the use of artificial insemination techniques means parents can only influence offspring quality via their gametes. Here we show that paternal aging reduces both the likelihood that eggs hatch and the rate at which chicks grow, with older males producing the lightest offspring after the first month. Surprisingly, this cost of paternal aging on offspring development is of a similar scale to that associated with maternal aging. Fitting with predictions on germline aging, the sperm of immature males produce the fastest growing offspring. Our findings thus indicate that any good genes benefit that might be offered by older 'proven' males will be eroded by aging of their germline DNA.

Maternal consumption of a cafeteria diet during lactation in rats leads the offspring to a thin-outside-fat-inside phenotype.

PubMed

Pomar, C A; van Nes, R; Sánchez, J; Picó, C; Keijer, J; Palou, A

2017-08-01

The suckling period is a critical phase of development, in which maternal overnutrition may program the susceptibility of developing chronic diseases and disorders, such as obesity and metabolic alterations, in adult life. Here, we questioned whether the consumption of a cafeteria diet throughout lactation in rats affects the macronutrient composition of milk and whether it results in permanent metabolic effects in the offspring. Nursing rats were fed a control diet or a cafeteria diet during lactation. Milk was obtained at different time points of lactation. Offspring (males and females) were weaned onto a control diet until the age of 6 months. Circulating parameters were measured under ad libitum feeding and under 12-h fasting conditions at weaning and at 3 and 6 months of age. An oral glucose tolerance test (OGTT) was performed at 3 and 6 months of age. Rats fed a cafeteria diet during lactation consumed an unbalanced diet, with lower protein and higher fat content versus controls, which was reflected in the composition of the milk. The offspring of rats fed a cafeteria diet during lactation showed lower body weight and lower lean mass, but greater fat accumulation, compared with controls. They also displayed hyperleptinaemia, altered lipid profile and impaired response to an OGTT. Maternal consumption of a cafeteria diet throughout lactation in rats produces lasting effects in the metabolic health of their offspring, which are not associated with a higher body weight but with a greater fat accumulation, similarly to the thin-outside-fat-inside phenotype.

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

PubMed Central

Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

2018-01-01

The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

PubMed Central

Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei

2018-01-01

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536

Clever mothers balance time and effort in parental care: a study on free-ranging dogs

PubMed Central

Sau, Shubhra

2017-01-01

Mammalian offspring require parental care, at least in the form of nursing during their early development. While mothers need to invest considerable time and energy in ensuring the survival of their current offspring, they also need to optimize their investment in one batch of offspring in order to ensure future reproduction and hence lifetime reproductive success. Free-ranging dogs live in small social groups, mate promiscuously and lack the cooperative breeding biology of other group-living canids. They face high early-life mortality, which in turn reduces fitness benefits of the mother from a batch of pups. We carried out a field-based study on free-ranging dogs in India to understand the nature of maternal care. Our analysis reveals that mothers reduce investment in energy-intensive active care and increase passive care as the pups grow older, thereby keeping overall levels of care more or less constant over pup age. Using the patterns of mother–pup interactions, we define the different phases of maternal care behaviour. PMID:28280555

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.

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.

The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

PubMed Central

Jahan-Mihan, Alireza; Rodriguez, Judith; Christie, Catherine; Sadeghi, Marjan; Zerbe, Tara

2015-01-01

The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring. PMID:26561832

Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood.

PubMed

Senko, Tomáš; Svitok, Pavel; Kršková, Lucia

2017-10-01

The intrauterine condition in which the mammalian foetus develops has an important role in prenatal programming. The aim of this study was to determine the extent to which activation of the maternal renin-angiotensin-aldosterone system (RAAS) could influence social behaviour strategies in offspring via changes in social neurotransmitters in the brain. Pregnant female Wistar rats were implanted with osmotic minipumps which continually released angiotensin II for 14 days at concentration of 2 μg/kg/h. The adult offspring (angiotensin and control groups) underwent a social interaction test. The mRNA expression of vasopressin, oxytocin and the oxytocin receptor in selected brain areas was measured by in situ hybridisation. Prenatal exposure to higher levels of angiotensin II resulted in a strong trend toward decreased total social interaction time and significantly decreased time spent in close proximity and frequency of mutual sniffing. The angiotensin group showed no changes in oxytocin mRNA expression in the hypothalamic paraventricular or supraoptic nuclei, but this group had reduced vasopressin mRNA expression in the same areas. We concluded that maternal activation of RAAS (via higher levels of angiotensin II) caused inhibition of some socio-cohesive indicators and decreased vasopressinergic activity of offspring. Taken together, these results suggest a reactive rather than proactive social coping strategy.

Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

PubMed

Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

2016-01-01

Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition.

Fetal growth restriction promotes physical inactivity and obesity in female mice.

PubMed

Baker, M S; Li, G; Kohorst, J J; Waterland, R A

2015-01-01

Environmental exposures during critical periods of prenatal and early postnatal life affect the development of mammalian body weight regulatory mechanisms, influencing lifelong risk of obesity. The specific biological processes that mediate the persistence of such effects, however, remain poorly understood. The objectives of this study were to determine the developmental timing and physiological basis of the obesity-promoting effect previously reported in offspring of obese agouti viable yellow (A(vy)/a) mothers. Newborn offspring of obese A(vy)/a and lean (a/a) mothers were cross-fostered shortly after birth to study separately the effects of in utero or suckling period exposure to A(vy)/a dams. Body composition, food intake, physical activity and energy expenditure were measured in offspring shortly after weaning and in adulthood. Offspring of obese A(vy)/a dams paradoxically experienced fetal growth restriction, which was followed by adult-onset obesity specifically in females. Our main analyses focused on wild-type (a/a) offspring, because a subset of adult A(vy)/a offspring contracted a kidney disease resembling diabetic nephropathy. Detailed physiological characterization demonstrated that, both shortly after weaning and in adulthood, female wild-type mice born to A(vy)/a mothers are not hyperphagic but have reduced physical activity and energy expenditure. No such coordinated changes were detected in male offspring. Mediational regression analysis of our longitudinal data supported a causal pathway in which fetal growth restriction persistently reduces physical activity, leading to adult obesity. Our data are consistent with several recent human epidemiological studies showing female-specific effects of perinatal nutritional restriction on later obesity, and provide the novel mechanistic insight that this may occur via permanent and sex-specific changes in one's inherent propensity for physical activity.

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 food intake and energy expenditure, increases anxiety like behavior and disturbs sleep patterns but not circadian rhythm in adult male offspring. PMID:28099477

A theoretical model of the evolution of maternal effects under parent-offspring conflict.

PubMed

Uller, Tobias; Pen, Ido

2011-07-01

The evolution of maternal effects on offspring phenotype should depend on the extent of parent-offspring conflict and costs and constraints associated with maternal and offspring strategies. Here, we develop a model of maternal effects on offspring dispersal phenotype under parent-offspring conflict to evaluate such dependence. In the absence of evolutionary constraints and costs, offspring evolve dispersal rates from different patch types that reflect their own, rather than the maternal, optima. This result also holds true when offspring are unable to assess their own environment because the maternal phenotype provides an additional source of information. Consequently, maternal effects on offspring diapause, dispersal, and other traits that do not necessarily represent costly resource investment are more likely to maximize offspring than maternal fitness. However, when trait expression was costly, the evolutionarily stable dispersal rates tended to deviate from those under both maternal and offspring control. We use our results to (re)interpret some recent work on maternal effects and their adaptive value and provide suggestions for future work. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

An Ancestral Recombination Graph for Diploid Populations with Skewed Offspring Distribution

PubMed Central

Birkner, Matthias; Blath, Jochen; Eldon, Bjarki

2013-01-01

A large offspring-number diploid biparental multilocus population model of Moran type is our object of study. At each time step, a pair of diploid individuals drawn uniformly at random contributes offspring to the population. The number of offspring can be large relative to the total population size. Similar “heavily skewed” reproduction mechanisms have been recently considered by various authors (cf. e.g., Eldon and Wakeley 2006, 2008) and reviewed by Hedgecock and Pudovkin (2011). Each diploid parental individual contributes exactly one chromosome to each diploid offspring, and hence ancestral lineages can coalesce only when in distinct individuals. A separation-of-timescales phenomenon is thus observed. A result of Möhle (1998) is extended to obtain convergence of the ancestral process to an ancestral recombination graph necessarily admitting simultaneous multiple mergers of ancestral lineages. The usual ancestral recombination graph is obtained as a special case of our model when the parents contribute only one offspring to the population each time. Due to diploidy and large offspring numbers, novel effects appear. For example, the marginal genealogy at each locus admits simultaneous multiple mergers in up to four groups, and different loci remain substantially correlated even as the recombination rate grows large. Thus, genealogies for loci far apart on the same chromosome remain correlated. Correlation in coalescence times for two loci is derived and shown to be a function of the coalescence parameters of our model. Extending the observations by Eldon and Wakeley (2008), predictions of linkage disequilibrium are shown to be functions of the reproduction parameters of our model, in addition to the recombination rate. Correlations in ratios of coalescence times between loci can be high, even when the recombination rate is high and sample size is large, in large offspring-number populations, as suggested by simulations, hinting at how to distinguish between different population models. PMID:23150600

Maternal depression and co-occurring antisocial behaviour: testing maternal hostility and warmth as mediators of risk for offspring psychopathology.

PubMed

Sellers, Ruth; Harold, Gordon T; Elam, Kit; Rhoades, Kimberly A; Potter, Robert; Mars, Becky; Craddock, Nick; Thapar, Anita; Collishaw, Stephan

2014-01-01

Disruption in the parent-child relationship is a commonly hypothesized risk factor through which maternal depression may increase risk for offspring psychopathology. However, maternal depression is commonly accompanied by other psychopathology, including antisocial behaviour. Few studies have examined the role of co-occurring psychopathology in depressed mothers. Using a longitudinal study of offspring of mothers with recurrent depression, we aimed to test whether maternal warmth/hostility mediated links between maternal depression severity and child outcomes, and how far direct and indirect pathways were robust to controls for co-occurring maternal antisocial behaviour. Mothers with a history of recurrent major depressive disorder and their adolescent offspring (9-17 years at baseline) were assessed three times between 2007 and 2010. Mothers completed questionnaires assessing their own depression severity and antisocial behaviour at Time 1 (T1). The parent-child relationship was assessed using parent-rated questionnaire and interviewer-rated 5-min speech sample at Time 2 (T2). Offspring symptoms of depression and disruptive behaviours were assessed using the Child and Adolescent Psychiatric Assessment at Time 3 (T3). Maternal hostility and warmth, respectively, mediated the association between maternal depression severity and risk for offspring psychopathology. However, the effects were attenuated when maternal antisocial behaviour was included in the analysis. In tests of the full theoretical model, maternal antisocial behaviour predicted both maternal hostility and low warmth, maternal hostility predicted offspring disruptive behaviour disorder symptoms, but not depression, and maternal warmth was not associated with either child outcome. Parenting interventions aimed at reducing hostility may be beneficial for preventing or reducing adolescent disruptive behaviours in offspring of depressed mothers, especially when depressed mothers report co-occurring antisocial behaviour. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

PubMed Central

Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

2013-01-01

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

Parental effects and flight behaviour in the burying beetle, Nicrophorus vespilloides

PubMed Central

Attisano, Alfredo; Kilner, Rebecca M.

2015-01-01

Parents play a key role in determining the phenotype of their offspring. However, relatively few studies have investigated whether parents can change their offspring's behaviour in a sustained way that persists into adulthood. With experiments on the burying beetle, Nicrophorus vespilloides, we investigated how the developmental environment created by parents affects their offspring's wing morphology in adulthood, and the correlated effects on adult flight behaviour. Burying beetles exhibit complex biparental care, but offspring can survive without parental provisioning. By removing parents just prior to hatching, while holding the nutritional environment constant, we investigated the downstream consequences for offspring morphology and behaviour. Larvae that developed in the absence of their parents had relatively long and more slender wings than those that developed in their parents' presence. Flight mill tests revealed that flight performance was dependent on the presence of parents during development but not on wing shape. Our results demonstrate that parents have long-lasting effects on the behaviour of their offspring, by influencing the morphology and flight behaviour of their young even after they have matured into adults. PMID:26681810

Examining Whether Offspring Psychopathology Influences Illness Course in Mothers With Recurrent Depression Using a High-Risk Longitudinal Sample

PubMed Central

2016-01-01

Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = −.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls’ symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression. PMID:26854510

Examining whether offspring psychopathology influences illness course in mothers with recurrent depression using a high-risk longitudinal sample.

PubMed

Sellers, Ruth; Hammerton, Gemma; Harold, Gordon T; Mahedy, Liam; Potter, Robert; Langley, Kate; Thapar, Ajay; Rice, Frances; Thapar, Anita; Collishaw, Stephan

2016-02-01

Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = -.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls' symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression. (c) 2016 APA, all rights reserved).

Fledgling survival increases with development time and adult survival across north and south temperate zones

USGS Publications Warehouse

Lloyd, Penn; Martin, Thomas E.

2016-01-01

Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

Parental Child-Rearing Conflicts Through Adolescence: Trajectories and Associations With Child Characteristics and Externalizing Patterns.

PubMed

Helland, Maren S; Kjeldsen, Anne; von Soest, Tilmann; Røysamb, Espen; Gustavson, Kristin; Nilsen, Wendy

2017-06-01

Research on longitudinal interparental conflict patterns and offspring development is scarce. The population-based TOPP study (N = 459) was used to investigate (1) child-rearing conflict trajectories through four time points during childhood and adolescence (ages 8-16), and (2) associations between conflict trajectories and child characteristics (i.e., birth order, gender, externalizing patterns from early childhood). Latent profile analysis identified six distinct trajectories. Conflict levels decreased for most respondents over the adolescent offspring period, but offspring's birth order and externalizing problems were related to less typical trajectories and higher levels of conflict. Onset of externalizing problems was of additional importance for the course of parental child-rearing conflicts. The results highlight the perception of the whole family as an interwoven system. © 2017 The Authors. Journal of Research on Adolescence © 2017 Society for Research on Adolescence.

Nutrition During Pregnancy Impacts Offspring's Epigenetic Status-Evidence from Human and Animal Studies.

PubMed

Geraghty, Aisling A; Lindsay, Karen L; Alberdi, Goiuri; McAuliffe, Fionnuala M; Gibney, Eileen R

2015-01-01

Pregnancy is a vital time of growth and development during which maternal nutrition significantly influences the future health of both mother and baby. During pregnancy, the fetus experiences a critical period of plasticity. Epigenetics, specifically DNA methylation, plays an important role here. As nutrition is influential for DNA methylation, this review aims to determine if maternal nutrition during pregnancy can modify the offspring's epigenome at birth. Research focuses on micronutrients and methyl donors such as folate and B vitamins. Evidence suggests that maternal nutrition does not largely influence global methylation patterns, particularly in nutrient-replete populations; however, an important impact on gene-specific methylation is observed. A link is shown between maternal nutrition and the methylome of the offspring; however, there remains a paucity of research. With the potential to use DNA methylation patterns at birth to predict health of the child in later life, it is vital that further research be carried out.

Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams

NASA Technical Reports Server (NTRS)

Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

2002-01-01

Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.

Do juveniles help or hinder? Influence of juvenile offspring on maternal behavior and reproductive outcomes in wild chimpanzees (Pan troglodytes).

PubMed

Stanton, Margaret A; Lonsdorf, Elizabeth V; Pusey, Anne E; Murray, Carson M

2017-10-01

Compared to great apes, humans maintain a relatively rapid reproductive pace despite long periods of dependency. This seemingly contradictory set of traits is made possible by weaning offspring before nutritional independence and alloparents who help provide care. In traditional societies, this help may be provided to mothers in part by their juvenile offspring who carry, supervise, or provision younger siblings. In contrast to humans, chimpanzees (Pan troglodytes) are nutritionally independent after weaning, yet juveniles continue to travel with their mother and younger sibling for an additional 4-5 years. This continued association could be costly to the mother if she continues to invest in weaned offspring. Alternately, while juvenile chimpanzees do not typically provision younger siblings, their presence and social interaction with infants may allow mothers to focus on other tasks. In this study, we investigate the costs and benefits to mothers of continued association with juveniles in wild chimpanzees. Using 26 years of long-term behavioral data we examined how maternal activity budgets varied based on the presence of a dependent juvenile offspring. We found that continued social interaction between mothers and juveniles does not influence the mother's time allocated to interacting with the younger infant, her feeding, resting, or travel time, or time socializing with other community members. Instead, mothers may benefit from the additional social interaction and/or relationship with their older offspring. Using 45 years of demographic data we found that those offspring who had an older sibling tended to be more likely to survive each year from birth to 8 years than those without an older sibling. Additionally, interbirth intervals were more likely to end when the female had an older offspring present. A mutually beneficial mother-juvenile dynamic in great apes provides insight into continued association between mothers and offspring after nutritional independence and the emergence of juvenile helping during hominin evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Disentangling prenatal and inherited influences in humans with an experimental design.

PubMed

Rice, Frances; Harold, Gordon T; Boivin, Jacky; Hay, Dale F; van den Bree, Marianne; Thapar, Anita

2009-02-17

Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

PubMed Central

Tucker, Deirdre K.; Macon, Madisa B.; Strynar, Mark J.; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E.

2015-01-01

Perfluorooctanoic acid (PFOA) is a known developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg), however, has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Mouse pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in exposed female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. In contrast, an evaluation of serum hormone levels and pubertal timing onset in the same offspring revealed no effects of PFOA compared to controls in either strain. Therefore, our data suggest that the mammary gland is more sensitive to the effects of early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. PMID:25499722

Comparative Developmental Staging of Female and Male Water Fleas Daphnia pulex and Daphnia magna During Embryogenesis.

PubMed

Toyota, Kenji; Hiruta, Chizue; Ogino, Yukiko; Miyagawa, Shinichi; Okamura, Tetsuro; Onishi, Yuta; Tatarazako, Norihisa; Iguchi, Taisen

2016-02-01

The freshwater crustacean genus Daphnia has been used extensively in ecological, developmental and ecotoxicological studies. Daphnids produce only female offspring by parthenogenesis under favorable conditions, but in response to various unfavorable conditions and external stimuli, they produce male offspring. Although we reported that exogenous exposure to juvenile hormones and their analogs can induce male offspring even under female-producing conditions, we recently established a male induction system in the Daphnia pulex WTN6 strain simply by changing day-length. This male and female induction system is suitable for understanding the innate mechanisms of sexual dimorphic development in daphnids. Embryogenesis has been described as a normal plate (developmental staging) in various daphnid species; however, all studies have mainly focused on female development. Here, we describe the developmental staging of both sexes during embryogenesis in two representative daphnids, D. pulex and D. magna, based on microscopic time-course observations. Our findings provide the first detailed insights into male embryogenesis in both species, and contribute to the elucidation of the mechanisms underlying sexual differentiation in daphnids.

Maternal antibody transfer can lead to suppression of humoral immunity in developing zebra finches (Taeniopygia guttata).

PubMed

Merrill, Loren; Grindstaff, Jennifer L

2014-01-01

Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female's plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring's humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipopolysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring's humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17-28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for 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.

Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years.

PubMed

Pearson, Rebecca M; Evans, Jonathan; Kounali, Daphne; Lewis, Glyn; Heron, Jon; Ramchandani, Paul G; O'Connor, Tom G; Stein, Alan

2013-12-01

Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention. To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression. Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring. Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision. Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression. The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

Parent and child psychopathology and suicide attempts among children of parents with alcohol use disorder.

PubMed

Conner, Kenneth R; Bossarte, Robert M; Lu, Naiji; Kaukeinen, Kimberly; Chan, Grace; Wyman, Peter; Tu, Xin M; Goldston, David B; Houston, Rebecca J; Bucholz, Kathleen K; Hesselbrock, Victor M

2014-01-01

Parents with psychopathology such as alcohol use disorder (AUD) that confers risk for suicide attempt (SA) may have children who are more likely to develop such psychopathology and to attempt suicide, suggesting that risk may be "transmitted" from parents to children. We examined this phenomenon during the transition from childhood to adolescence, when risk for SA increases dramatically. A cohort of 418 children were examined at average age 9.4 (range 7-14) years at enrollment (Time 1, childhood) and approximately 5 years later, prior to reaching age 18 (Time 2, adolescence). One or both biological parents, oversampled for AUD, were also interviewed. Structural equation models (SEM) examined father-child, mother-child, and either/both parent-child associations. The primary outcome was SA over follow-up among offspring, assessed at Time 2. As hypothesized, parental antisocial personality disorder predicted conduct disorder symptoms in offspring both during childhood and adolescence (parent-child model, father-child model) and maternal AUD predicted conduct disorder symptoms during childhood (mother-child model). However, we did not find evidence to support transmission of depression from parents to offspring either during childhood or adolescence, and parent psychopathology did not show statistically significant associations with SA during adolescence. In conclusion, we conducted a rare study of parent-to-child "transmission" of risk for SA that used a prospective research design, included diagnostic interviews with both parents and offspring, and examined the transition from childhood to adolescence, and the first such study in children of parents with AUD. Results provided mixed support for hypothesized parent-child associations.

Parent and Child Psychopathology and Suicide Attempts among Children of Parents with Alcohol Use Disorder

PubMed Central

Conner, Kenneth R.; Bossarte, Robert M.; Lu, Naiji; Kaukeinen, Kimberly; Chan, Grace; Wyman, Peter; Tu, Xin M.; Goldston, David B.; Houston, Rebecca J.; Bucholz, Kathleen K.; Hesselbrock, Victor M.

2014-01-01

Parents with psychopathology such as alcohol use disorder (AUD) that confers risk for suicide attempt (SA) may have children who are more likely to develop such psychopathology and to attempt suicide, suggesting that risk may be “transmitted” from parents to children. We examined this phenomenon during the transition from childhood to adolescence, when risk for SA increases dramatically. A cohort of 418 children were examined at average age 9.4 (range 7–14) years at enrollment (Time 1, childhood) and approximately five years later, prior to reaching age 18 (Time 2, adolescence). One or both biological parents, oversampled for AUD, were also interviewed. Structural equation models (SEM) examined father-child, mother-child, and either/both parent-child associations. The primary outcome was SA over follow-up among offspring, assessed at Time 2. As hypothesized, parental antisocial personality disorder predicted conduct disorder symptoms in offspring both during childhood and adolescence (parent-child model, father-child model) and maternal AUD predicted conduct disorder symptoms during childhood (mother-child model). However, we did not find evidence to support transmission of depression from parents to offspring either during childhood or adolescence, and parent psychopathology did not show statistically significant associations with SA during adolescence. In conclusion, we conducted a rare study of parent-to-child “transmission” of risk for SA that used a prospective research design, included diagnostic interviews with both parents and offspring, and examined the transition from childhood to adolescence, and the first such study in children of parents with AUD. Results provided mixed support for hypothesized parent-child associations. PMID:24716789

Individual birds advance offspring hatching in response to increased temperature after the start of laying.

PubMed

Vedder, Oscar

2012-11-01

In seasonally reproducing organisms, timing reproduction to match food availability is key to individual fitness. Ambient temperature functions as an important cue for the timing of the food peak in temperate-zone birds. After laying start, individual birds may still improve synchrony between offspring hatching and food availability by adjusting the onset of incubation to most up-to-date cues about the development of the food source. However, it is unknown whether individuals respond to changes in temperature after the onset of laying, and whether individuals adjust incubation onset independent of clutch size. Here, I show in free-living blue tits (Cyanistes caeruleus) that experimental heating of nestboxes in the laying phase resulted in increased duration of nocturnal incubation bouts prior to clutch completion, leading to earlier hatching of eggs and increased hatching asynchrony. Experimental heating did not affect the number of laying gaps, egg volume and clutch size, nor were any carry-over effects on offspring detected. These results are best explained as a response to increased temperature acting as a cue for an advanced food-peak, rather than a relief of energetic constraints, because improved energetic conditions would not favour more hatching asynchrony. Other benefits cannot be excluded, since increased laying-phase incubation under warmer conditions may also help maintain egg viability. This study is the first to show that temperature has a causal effect on the time between clutch completion and hatching of the first offspring, indicating that behavioural adjustment to climate change can continue after laying start.

Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.

PubMed

Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

2008-08-22

Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

ADVERSE EFFECTS OF PRENATAL EXPOSURE TO ATRAZINE DURING A CRITICAL PERIOD OF MAMMARY GLAND GROWTH

EPA Science Inventory

Prenatal exposure to 100 mg/kg atrazine (ATR) was previously shown to delay mammary gland (MG) development in the female offspring of Long Evans (LE) rats. To determine if the fetal MG was most sensitive to ATR effects during specific periods of development, timed-pregnant dams ...

“What are my chances of developing COPD if one of my parents has the disease?” A systematic review and meta-analysis of prevalence of co-occurrence of COPD diagnosis in parents and offspring

PubMed Central

Li, Lok Sze Katrina; Paquet, Catherine; Johnston, Kylie; Williams, Marie T

2017-01-01

Introduction Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to life course factors. Consequently, adult offspring of parents with COPD may be at a greater risk of developing COPD. The aim of this study was to review the prevalence of co-occurrence of COPD in adult offspring with one or both parents having COPD independent of specific genetic variations. Methods In total, five databases were searched for original studies in which prevalence of COPD was reported in both offspring (children) and one or both parents. Studies were excluded if COPD was not clearly defined, COPD was linked to specific genetic variations, COPD was combined with other chronic respiratory conditions, or estimates included other first-degree relatives. Data extraction (ie, sample characteristics, prevalence of COPD, and odds ratio [OR] if reported) was completed by two independent reviewers. A meta-analysis of prevalence and OR was conducted, where possible. Results Of the 3,382 citations, 129 full texts were reviewed to include eight studies (six case–control, one cross-sectional, and one cohort) reflecting either prevalence of COPD in offspring of parents with COPD (descendent approach, n=3), which ranged from 0% to 17.3%, or prevalence of people with COPD reporting positive parental history of COPD (antecedent approach, n=5), for which the pooled prevalence was 28.6%. Offspring of people with COPD had 1.57 times greater odds (95% confidence interval =1.29–1.93; P<0.001) of having COPD compared with people not having a parental history of COPD. Conclusion The prevalence of COPD in adult offspring of people with COPD is greater than population-based estimates, and the ORs indicate a higher risk in this group. This offers clinicians a potential strategy for opportunistic screening, early identification, and intervention in this at-risk group. PMID:28182144

Prenatal cadmium exposure alters postnatal immune cell development and function

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

Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal

2012-06-01

Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspringmore » were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental effects on the immune system of the offspring and these effects are to some extent sex-specific. -- Highlights: ► Prenatal exposure to Cd causes no thymocyte phenotype changes in the offspring ► Analysis of the splenocyte phenotype demonstrates a macrophage-specific effect only in male offspring ► The cytokine profiles suggest an effect on peripheral Th1 cells in female and to a lesser degree in male offspring ► There was a marked increase in serum anti-streptococcal antibody levels after immunization in both sexes ► There was a marked decrease in the numbers of splenic CD8{sup +}CD223{sup +} cells in both sexes.« less

Development of an animal model of fibrous cholangitis in pigs.

PubMed

Lainakis, Nektarios G; Papalois, Apostolos; Agrogiannis, Georgios; Antonopoulos, Constantine N; Michail, Panagiotis; Bastounis, Elias; Patsouris, Efstathios; Felekouras, Evangelos

2014-04-01

The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0-5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Statistically significant differences were observed for most of the histopathological markers between the group of pigs' offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

Estimating SIT-driven population reduction in the Mediterranean fruit fly, Ceratitis capitata, from sterile mating.

PubMed

Juan-Blasco, M; Sabater-Muñoz, B; Pla, I; Argilés, R; Castañera, P; Jacas, J A; Ibáñez-Gual, M V; Urbaneja, A

2014-04-01

Area-wide sterile insect technique (SIT) programs assume that offspring reduction of the target population correlates with the mating success of the sterile males released. However, there is a lack of monitoring tools to prove the success of these programs in real-time. Field-cage tests were conducted under the environmental conditions of the Mediterranean coast of Spain to estimate: (a) the mating success of sterile Vienna-8 (V8) Ceratitis capitata males using molecular markers and (b) their efficacy to reduce C. capitata populations under six release ratios of wild females to wild males to V8 males (1:0:0, 1:1:0, 1:1:1, 1:1:5, 1:1:10, and 1:1:20). Statistical models were developed to predict: (a) the number of females captured in traps, (b) sperm ID (sterile or not) in spermathecae of the trapped females, and (c) the viable offspring produced, using release ratio and temperature as predictors. The number of females captured was affected by relative humidity. However, its influence in the model was low. Female captures were significantly higher in ratios 1:0:0 compared to ratios where V8 males were released. The proportion of V8 sperm in spermathecae increased with temperature and with the number of V8 males released, but leveled off between ratios 1:1:10 and 1:1:20. In all seasons, except winter (no offspring), viable offspring increased with temperature and was lowest for ratio 1:1:20. For the first time, a strong negative relationship between proportion of V8 sperm detected by molecular tools and C. capitata offspring was established. The models obtained should contribute to enhance the efficacy of SIT programs against this pest.

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…

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.

The role of maternal obesity in the risk of neuropsychiatric disorders

PubMed Central

Rivera, Heidi M.; Christiansen, Kelly J.; Sullivan, Elinor L.

2015-01-01

Recent evidence indicates that perinatal exposure to maternal obesity, metabolic disease, including diabetes and hypertension, and unhealthy maternal diet has a long-term impact on offspring behavior and physiology. During the past three decades, the prevalence of both obesity and neuropsychiatric disorders has rapidly increased. Epidemiologic studies provide evidence that maternal obesity and metabolic complications increase the risk of attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, anxiety, depression, schizophrenia, eating disorders (food addiction, anorexia nervosa, and bulimia nervosa), and impairments in cognition in offspring. Animal models of maternal high-fat diet (HFD) induced obesity also document persistent changes in offspring behavior and impairments in critical neural circuitry. Animals exposed to maternal obesity and HFD consumption display hyperactivity, impairments in social behavior, increased anxiety-like and depressive-like behaviors, substance addiction, food addiction, and diminished cognition. During development, these offspring are exposed to elevated levels of nutrients (fatty acids, glucose), hormones (leptin, insulin), and inflammatory factors (C-reactive protein, interleukin, and tumor necrosis factor). Such factors appear to permanently change neuroendocrine regulation and brain development in offspring. In addition, inflammation of the offspring brain during gestation impairs the development of neural pathways critical in the regulation of behavior, such as serotoninergic, dopaminergic, and melanocortinergic systems. Dysregulation of these circuits increases the risk of mental health disorders. Given the high rates of obesity in most developed nations, it is critical that the mechanisms by which maternal obesity programs offspring behavior are thoroughly characterized. Such knowledge will be critical in the development of preventative strategies and therapeutic interventions. PMID:26150767

A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat

PubMed Central

Zambrano, E; Bautista, C J; Deás, M; Martínez-Samayoa, P M; González-Zamorano, M; Ledesma, H; Morales, J; Larrea, F; Nathanielsz, P W

2006-01-01

Extensive epidemiological and experimental evidence indicates that a sub-optimal environment during fetal and neonatal development in both humans and animals may programme offspring susceptibility to later development of chronic diseases including obesity and diabetes that are the result of altered carbohydrate metabolism. We determined the effects of protein restriction during pregnancy and/or lactation on growth, serum leptin, and glucose and insulin responses to a glucose tolerance test in male and female offspring at 110 days postnatal life. We fed Wistar rats a normal control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. Female but not male R pups weighed less than C at birth. After delivery, mothers received the C or R diet during lactation to provide four offspring groups: CC (first letter maternal pregnancy diet and second maternal lactation diet), RR, CR and RC. All offspring were fed ad libitum with C diet after weaning. Relative food intake correlated inversely with weight. Offspring serum leptin correlated with body weight and relative, but not absolute, food intake in both male and female pups. Serum leptin was reduced in RR female pups compared with CC and increased in RC males compared with CC at 110 days of age. Offspring underwent a glucose tolerance test (GTT) at 110 days postnatal life. Female RR and CR offspring showed a lower insulin to glucose ratio than CC. At 110 days of age male RR and CR also showed some evidence of increased insulin sensitivity. Male but not female RC offspring showed evidence of insulin resistance compared with CC. Cholesterol was similar and triglycerides (TG) higher in male compared with female CC. Cholesterol and TG were higher in males than females in RR, CR and RC (P < 0.05). Cholesterol and TG did not differ between groups in females. Cholesterol and TG were elevated in RC compared with CC males. Nutrient restriction in lactation increased relative whole protein and decreased whole lipid in both males and females. RC females showed decreased relative levels of protein and increased fat. We conclude that maternal protein restriction during either pregnancy and/or lactation alters postnatal growth, appetitive behaviour, leptin physiology, TG and cholesterol concentrations and modifies glucose metabolism and insulin resistance in a sex- and time window of exposure-specific manner. PMID:16339179

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. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats.

PubMed

Sen, Sarbattama; Simmons, Rebecca A

2010-12-01

Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

Characteristics of depression among offspring at high and low familial risk of bipolar disorder.

PubMed

Diler, Rasim Somer; Goldstein, Tina R; Hafeman, Danella; Rooks, Brian Thomas; Sakolsky, Dara; Goldstein, Benjamin I; Monk, Kelly; Hickey, Mary Beth; Axelson, David; Iyengar, Satish; Birmaher, Boris

2017-08-01

Having a parent with bipolar disorder (BP) is a very strong risk factor for developing BP. Similarly, depression among youth is a clinical risk factor for subsequent BP. We evaluated whether mood symptomatology in depressed youth is different between those at high and low familial risk to develop BP. The most severe major depressive episode in BP offspring (N=61) and community control offspring (N=20) was evaluated using expanded depression and mania rating scales derived from the Schedule for Affective Disorders and Schizophrenia for Children Present Version. The results were adjusted for any between-group significant demographic differences and for multiple comparisons. The severity of depressive symptoms and the percentage of offspring with severe depressive symptoms, especially atypical depressive features, were significantly higher in the depressed offspring of BP parents compared to the depressed controls (P s <.05). The depressive symptoms were helpful to identify a high-risk group (e.g., odds ratio [OR] for hypersomnia: 22.4, 95% confidence interval [CI]: 1.3-404, P=.04). In addition, there were significantly more depressed offspring of BP parents with subsyndromal manic symptoms than controls (52.5% vs 20%, OR: 4.2, 95% CI: 1.2-14.7, P<.01). Depressed BP offspring had more severe depression including atypical depressive symptoms, and were more likely to have subsyndromal mixed manic symptoms than depressed control offspring. Prospective studies to evaluate whether these youth are at high risk to develop BP are warranted. If replicated, the results of this study have important clinical (e.g., treatment of depression in depressed offspring of BP parents) and research implications. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Paternal effects on offspring fitness in a multimale primate society

PubMed Central

Charpentier, M. J. E.; Van Horn, R. C.; Altmann, J.; Alberts, S. C.

2008-01-01

When females mate with multiple males, paternal care is generally expected to be negligible, because it may be difficult or impossible for males to discriminate their own offspring from those of other males, and because engaging in paternal care may reduce male mating opportunities. Consequently, males in multimale societies are not predicted to provide direct benefits to their offspring. We have recently demonstrated, however, that males in a typical multimale primate society (yellow baboons, Papio cynocephalus) discriminate their own offspring from those of other males and provide care to them in the form of repeated support during agonistic encounters. This observation raises the question of whether fathers enhance offspring fitness in this species. Here we use 30 years of data on age at maturity for 118 yellow baboons with known fathers. We show that the father's presence in the offspring's social group during the offspring's immature period accelerated the timing of physiological maturation in daughters. Sons also experienced accelerated maturation if their father was present during their immature period, but only if the father was high ranking at the time of their birth. Because age at reproductive maturity has a large impact on lifetime reproductive success, our results indicate a direct effect of paternal presence on offspring fitness. This relationship in turn suggests that the multiple roles that males play in multimale animal societies have not been sufficiently examined or appreciated and that paternal effects may be more pervasive than previously appreciated. PMID:18250308

Effects of paternal obesity on growth and adiposity of male rat offspring.

PubMed

Lecomte, Virginie; Maloney, Christopher A; Wang, Kristy W; Morris, Margaret J

2017-02-01

Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk. Copyright © 2017 the American Physiological Society.

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

Effects of nutritional deprivation on development and behavior in the subsocial bee Ceratina calcarata (Hymenoptera: Xylocopinae).

PubMed

Lawson, Sarah P; Helmreich, Salena L; Rehan, Sandra M

2017-12-01

By manipulating resources or dispersal opportunities, mothers can force offspring to remain at the nest to help raise siblings, creating a division of labor. In the subsocial bee Ceratina calcarata , mothers manipulate the quantity and quality of pollen provided to the first female offspring, producing a dwarf eldest daughter that is physically smaller and behaviorally subordinate. This daughter forages for her siblings and forgoes her own reproduction. To understand how the mother's manipulation of pollen affects the physiology and behavior of her offspring, we manipulated the amount of pollen provided to offspring and measured the effects of pollen quantity on offspring development, adult body size and behavior. We found that by experimentally manipulating pollen quantities we could recreate the dwarf eldest daughter phenotype, demonstrating how nutrient deficiency alone can lead to the development of a worker-like daughter. Specifically, by reducing the pollen and nutrition to offspring, we significantly reduced adult body size and lipid stores, creating significantly less aggressive, subordinate individuals. Worker behavior in an otherwise solitary bee begins to explain how maternal manipulation of resources could lead to the development of social organization and reproductive hierarchies, a major step in the transition to highly social behaviors. © 2017. Published by The Company of Biologists Ltd.

Embryonic developmental plasticity in the long-snouted seahorse (Hippocampus reidi, Ginsburg 1933) in relation to parental preconception diet.

PubMed

Otero-Ferrer, Francisco; Izquierdo, Marisol; Fazeli, Alireza; Holt, William V

2016-06-01

The aim of the present study was to investigate the hypothesis that parental periconception nutrition in adult seahorses affects the development and growth of their offspring. We tested the hypothesis that because seahorse embryos develop inside the male's brood pouch, manipulation of the male's diet would affect offspring growth and development independently of the female's diet. Adult males and females were fed separately with either wild-caught crustaceans or commercial aquarium diet for 1 month before conception to influence the periconception environment. Approximately 10000 offspring were obtained from four different treatment groups (Male/Wild or Male/Commercial×Female/Wild or Female/Commercial). Weights, physical dimensions and fatty acid profiles of the newborns were determined. Offspring produced when the males receiving commercial diet were mated with wild-fed females were larger (P<0.05) than those produced by wild-fed males. When both males and females were fed with commercial diet, their offspring were significantly smaller than those from the other treatment groups. When commercial diet-fed females were mated with wild-fed males, the offspring showed distortion of the snout:head length ratio. These results support the view that the preconception diet received by males and females differentially affects embryonic development.

Childhood verbal abuse and risk for personality disorders during adolescence and early adulthood.

PubMed

Johnson, J G; Cohen, P; Smailes, E M; Skodol, A E; Brown, J; Oldham, J M

2001-01-01

Data from a community-based longitudinal study were used to investigate whether childhood verbal abuse increases risk for personality disorders (PDs) during adolescence and early adulthood. Psychiatric and psychosocial interviews were administered to a representative community sample of 793 mothers and their offspring from two New York State counties in 1975, 1983, 1985 to 1986, and 1991 to 1993, when the mean ages of the offspring were 5, 14, 16, and 22 years, respectively. Data regarding childhood abuse and neglect were obtained from the psychosocial interviews and from official New York State records. Offspring who experienced maternal verbal abuse during childhood were more than three times as likely as those who did not experience verbal abuse to have borderline, narcissistic, obsessive-compulsive, and paranoid PDs during adolescence or early adulthood. These associations remained significant after offspring temperament, childhood physical abuse, sexual abuse, neglect, physical punishment during childhood, parental education, parental psychopathology, and co-occurring psychiatric disorders were controlled statistically. In addition, youths who experienced childhood verbal abuse had elevated borderline, narcissistic, paranoid, schizoid, and schizotypal PD symptom levels during adolescence and early adulthood after the covariates were accounted for. These findings suggest that childhood verbal abuse may contribute to the development of some types of PDs, independent of offspring temperament, childhood physical abuse, sexual abuse, neglect, physical punishment during childhood, parental education, parental psychopathology, and co-occurring psychiatric disorders.

Maternal Exercise Improves the Metabolic Health of Adult Offspring.

PubMed

Harris, Johan E; Baer, Lisa A; Stanford, Kristin I

2018-03-01

The intrauterine environment can modulate the course of development and confer an enduring effect on offspring health. The effects of maternal diet to impair offspring metabolic health are well established, but the effects of maternal exercise on offspring metabolic health have been less defined. Because physical exercise is a treatment for obesity and type 2 diabetes (T2D), maternal exercise is an appealing intervention to positively influence the intrauterine environment and improve the metabolic health of offspring. Recent research has provided insights into the effects of maternal exercise on the metabolic health of adult offspring, which is the focus of this review. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diet and density dependent competition affect larval performance and oviposition site selection in the mosquito species Aedes albopictus (Diptera: Culicidae)

PubMed Central

2012-01-01

Background Oviposition-site choice is an essential component of the life history of all mosquito species. According to the oviposition-preference offspring-performance (P-P) hypothesis, if optimizing offspring performance and fitness ensures high overall reproductive fitness for a given species, the female should accurately assess details of the heterogeneous environment and lay her eggs preferentially in sites with conditions more suitable to offspring. Methods We empirically tested the P-P hypothesis using the mosquito species Aedes albopictus by artificially manipulating two habitat conditions: diet (measured as mg of food added to a container) and conspecific density (CD; number of pre-existing larvae of the same species). Immature development (larval mortality, development time to pupation and time to emergence) and fitness (measured as wing length) were monitored from first instar through adult emergence using a factorial experimental design over two ascending gradients of diet (2.0, 3.6, 7.2 and 20 mg food/300 ml water) and CD (0, 20, 40 and 80 larvae/300 ml water). Treatments that exerted the most contrasting values of larval performance were recreated in a second experiment consisting of single-female oviposition site selection assay. Results Development time decreased as food concentration increased, except from 7.2 mg to 20.0 mg (Two-Way CR ANOVA Post-Hoc test, P > 0.1). Development time decreased also as conspecific density increased from zero to 80 larvae (Two-Way CR ANOVA Post-Hoc test, P < 0.5). Combined, these results support the role of density-dependent competition for resources as a limiting factor for mosquito larval performance. Oviposition assays indicated that female mosquitoes select for larval habitats with conspecifics and that larval density was more important than diet in driving selection for oviposition sites. Conclusions This study supports predictions of the P-P hypothesis and provides a mechanistic understanding of the underlying factors driving mosquito oviposition site selection. PMID:23044004

Effects of maternal stress during pregnancy on learning and memory via hippocampal BDNF, Arc (Arg3.1) expression in offspring.

PubMed

Guan, Su-Zhen; Ning, Li; Tao, Ning; Lian, Yu-Long; Liu, Ji-Wen; Ng, Tzi Bun

2016-09-01

The intrauterine environment has a significant long-term impact on individual's life, this study was designed to investigate the effect of stress during pregnancy on offspring's learning and memory abilities and analyze its mechanisms from the expression of BDNF and Arc in the hippocampus of the offspring. A rat model of maternal chronic stress during pregnancy was mating from 3rd day during been subjecting to chronic unpredictable mild stress (CUMS). The body weights and behavioral changes were recorded, and plasma corticosterone levels were determined by radioimmunoassay. The learning and memory abilities of the offspring were measured by Morris water maze testing from PND 42. The expression of hippocampal BDNF and Arc mRNA and protein were respectively measured using RT-PCR and Western blotting. Results indicated that an elevation was observed in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy, a reduction in the crossing and rearing movement times and the preference for sucrose. The body weight of maternal stress's offspring was lower than the control group, and the plasma corticosterone level was increased. Chronic stress during pregnancy had a significant impact on the spatial learning and memory of the offspring. The expression of BDNF mRNA and protein, Arc protein in offspring of maternal stress during pregnancy was attenuated and some relationships existed between these parameters. Collectively, these findings disclose that long-time maternal stress during pregnancy could destroy spatial learning and memory abilities of the offspring, the mechanism of which is related to been improving maternal plasma corticosterone and reduced hippocampal BDNF, Arc of offspring rats. Copyright © 2016. Published by Elsevier B.V.

Chronic maternal low-protein diet in mice affects anxiety, night-time energy expenditure and sleep patterns, but not circadian rhythm in male offspring

USDA-ARS?s Scientific Manuscript database

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 decre...

Evaluation of emotional behaviors in young offspring of C57BL/6J mice after gestational and/or perinatal exposure to nicotine in six different time-windows.

PubMed

Alkam, Tursun; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Mamiya, Takayoshi; Aoyama, Yuki; Nitta, Atsumi; Yamada, Kiyofumi; Nabeshima, Toshitaka

2013-02-15

Nicotine replacement treatments are being alternatively applied as an aid to smoking cessation during pregnancy. However, the effects of nicotine exposed at the prenatal stage on the emotional behaviors in offspring are not well understood due to the lack of systematic investigations. The current study has therefore initially aimed to evaluate emotional behaviors in young mouse offspring (postnatal day 28-36) which experienced gestational and/or perinatal nicotine exposure (GPNE) in six different time-windows. Pregnant C57BL/6J mice were exposed to nicotine via sweetened (2% sucrose) drinking water during 6 different time-windows including gestational day 0-day 13 (G0-G13), G14-perinatal day 0 (P0), G0-P0, G14-P7, G0-P7, and P0-P7. During P28-P36 days, both male and female offspring were given a battery of behavioral tests including light and dark box test, marble burying behavior test, novelty-suppressed feeding test, sociability and social novelty preference test, social avoidance tube test, and elevated plus maze test. GPNE during G0-P0, G14-P0, G14-P7, and G0-P7 induced abnormal behaviors in male and female offspring to different extent. Results indicated that nicotine at any time points of gestational and/or perinatal period impairs emotional behaviors in offspring, and suggested certain time-windows for further neurochemical or molecular studies in relation with GPNE-induced emotional abnormalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Maternal high-fat feeding leads to alterations of brain glucose metabolism in the offspring: positron emission tomography study in a porcine model.

PubMed

Sanguinetti, Elena; Liistro, Tiziana; Mainardi, Marco; Pardini, Silvia; Salvadori, Piero A; Vannucci, Alessandro; Burchielli, Silvia; Iozzo, Patricia

2016-04-01

Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p < 0.05), and severe glycogen depletion, lasting until adulthood. Maternal high-fat feeding leads to brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.

Don't put all your eggs in one nest: spread them and cut time at risk.

PubMed

Andersson, Malte; Åhlund, Matti

2012-09-01

In many egg-laying animals, some females spread their clutch among several nests. The fitness effects of this reproductive tactic are obscure. Using mathematical modeling and field observations, we analyze an unexplored benefit of egg spreading in brood parasitic and other breeding systems: reduced time at risk for offspring. If a clutch takes many days to lay until incubation and embryo development starts after the last egg, by spreading her eggs a parasitic female can reduce offspring time in the vulnerable nest at risk of predation or other destruction. The model suggests that she can achieve much of this benefit by spreading her eggs among a few nests, even if her total clutch is large. Field data from goldeneye ducks Bucephala clangula show that egg spreading enables a fecund female to lay a clutch that is much larger than average without increasing offspring time at risk in a nest. This advantage increases with female condition (fecundity) and can markedly raise female reproductive success. These results help explain the puzzle of nesting parasites in some precocial birds, which lay eggs in the nests of other females before laying eggs in their own nest. Risk reduction by egg spreading may also play a role in the evolution of other breeding systems and taxa-for instance, polyandry with male parental care in some birds and fishes.

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

PubMed

Nuñez, P; Fernandez, T; García-Arévalo, M; Alonso-Magdalena, P; Nadal, A; Perillan, C; Arguelles, J

2018-04-01

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

PubMed Central

Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

2015-01-01

BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients

PubMed Central

Fiorentini, A; Perciaccante, A; Paris, A; Serra, P; Tubani, L

2005-01-01

The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance. PMID:16197556

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 risk for stress-related pathology. PMID:25071719

In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

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

Wang, Wei, E-mail: weiwang2@illinois.edu; Hafner, Katlyn S., E-mail: katlynhafner@gmail.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestationalmore » day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in female mouse offspring.« less

Familial Pathways to Early-Onset Suicidal Behavior: Familial and Individual Antecedents of Suicidal Behavior

PubMed Central

Melhem, Nadine M.; Brent, David A.; Ziegler, Melissa; Iyengar, Satish; Kolko, David; Oquendo, Maria; Birmaher, Boris; Burke, Ainsley; Zelazny, Jamie; Stanley, Barbara; Mann, J. John

2013-01-01

Objective The authors sought to identify clinical predictors of new-onset suicidal behavior in children of parents with a history of mood disorder and suicidal behavior. Method In a prospective study of offspring of parents with mood disorders, 365 offspring (average age, 20 years) of 203 parents were followed for up to 6 years. Offspring with incident suicide attempts or emergency referrals for suicidal ideation or behavior (“incident events”) were compared with offspring without such events on demographic and clinical characteristics. Multivariate analyses were conducted to examine predictors of incident events and predictors of time to incident event. Results Offspring of probands who had made suicide attempts, compared with offspring of parents with mood disorders who had not made attempts, had a higher rate of incident suicide attempts (4.1% versus 0.6%, relative risk=6.5) as well as overall suicidal events (8.3% versus 1.9%, relative risk=4.4). Mood disorder and self-reported impulsive aggression in offspring and a history of sexual abuse and self-reported depression in parents predicted earlier time to, and greater hazard of, an incident suicidal event. Conclusions In offspring of parents with mood disorders, precursors of early-onset suicidal behavior include mood disorder and impulsive aggression as well as parental history of suicide attempt, sexual abuse, and self-reported depression. These results suggest that efforts to prevent the familial transmission of early-onset suicidal behavior by targeting these domains could reduce the morbidity of suicidal behavior in high-risk youths. PMID:17728421

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

Programming of mouse obesity by maternal exposure to concentrated ambient fine particles.

PubMed

Chen, Minjie; Wang, Xiaoke; Hu, Ziying; Zhou, Huifen; Xu, Yanyi; Qiu, Lianglin; Qin, Xiaobo; Zhang, Yuhao; Ying, Zhekang

2017-06-23

Many diseases including obesity may originate through alterations in the early-life environment that interrupts fetal development. Increasing evidence has shown that exposure to ambient fine particles (PM 2.5 ) is associated with abnormal fetal development. However, its long-term metabolic effects on offspring have not been systematically investigated. To determine if maternal exposure to PM 2.5 programs offspring obesity, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) during pre-conception, pregnancy, and lactation, and the developmental and metabolic responses of offspring were assessed. The growth trajectory of offspring revealed that maternal exposure to CAP significantly decreased offspring birth weight but increased body weight of adult male but not female offspring, and the latter was expressed as increased adiposity. These adult male offspring had increased food intake, but were sensitive to exogenous leptin. Their hypothalamic expression of Socs3 and Pomc, two target genes of leptin, was not changed, and the hypothalamic expression of NPY, an orexigenic peptide that is inhibited by leptin, was significantly increased. These decreases in central anorexigenic signaling were accompanied by reduced plasma leptin and its expression in adipose tissues, the primary source of circulating leptin. In contrast, maternal exposure did not significantly change any of these indexes in adult female offspring. Pyrosequencing demonstrated that the leptin promoter methylation of adipocytes was significantly increased in CAP-exposed male but not female offspring. Our data indicate that maternal exposure to ambient PM 2.5 programs obesity in male offspring probably through alterations in the methylation of the promoter region of the leptin gene.

Offspring of Parents with Chronic Pain: A Systematic Review and Meta-Analysis of Pain, Health, Psychological, and Family Outcomes

PubMed Central

Higgins, Kristen S.; Birnie, Kathryn A.; Chambers, Christine T.; Wilson, Anna C.; Caes, Line; Clark, Alexander J.; Lynch, Mary; Stinson, Jennifer; Campbell-Yeo, Marsha

2015-01-01

Offspring of parents with chronic pain may be at risk for poorer outcomes than offspring of healthy parents. The objective of this research was to provide a comprehensive mixed-methods, systematic synthesis of all available research on outcomes in offspring of parents with chronic pain. A systematic search was conducted for published articles in English examining pain, health, psychological, or family outcomes in offspring of parents with chronic pain. Fifty-nine eligible articles were identified (31 population-based, 25 clinical, 3 qualitative), including offspring from birth to adulthood and parents with varying chronic pain diagnoses (e.g., mixed pain samples, arthritis). Meta-analysis was used to synthesize the results from population-based and clinical studies, while meta-ethnography was used to synthesize the results of qualitative studies. Increased pain complaints were found in offspring of mothers and of fathers with chronic pain, and when both parents had chronic pain. Newborns of mothers with chronic pain were more likely to have adverse birth outcomes, including low birthweight, preterm delivery, caesarean section, intensive care admission, and mortality. Offspring of parents with chronic pain had greater externalizing and internalizing problems and poorer social competence and family outcomes. No significant differences were found on teacher-reported externalizing problems. The meta-ethnography identified six key concepts (developing independence, developing compassion, learning about health and coping, missing out, emotional health, and struggles communicating with parents). Across study designs, offspring of parents with chronic pain had poorer outcomes than other offspring, although the meta-ethnography noted some constructive impact of having a parent with chronic pain. PMID:26172553

Moderate daily exercise activates metabolic flexibility to prevent prenatally induced obesity.

PubMed

Miles, Jennifer L; Huber, Korinna; Thompson, Nichola M; Davison, Michael; Breier, Bernhard H

2009-01-01

Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase Czeta levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

Pubertal Timing and Early Sexual Intercourse in the Offspring of Teenage Mothers

ERIC Educational Resources Information Center

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

2011-01-01

Early puberty is associated with stressful family environments, early sexual intercourse, and teenage pregnancy. We examined pubertal timing and sexual debut among the 14-year-old offspring of teenage mothers. Mothers (71% Black, 29% White) were recruited as pregnant teenagers (12-18 years old). Data were collected during pregnancy and when…

Genome-wide DNA Methylation Changes in a Mouse Model of Infection-Mediated Neurodevelopmental Disorders.

PubMed

Richetto, Juliet; Massart, Renaud; Weber-Stadlbauer, Ulrike; Szyf, Moshe; Riva, Marco A; Meyer, Urs

2017-02-01

Prenatal exposure to infectious or inflammatory insults increases the risk of neurodevelopmental disorders. Using a well-established mouse model of prenatal viral-like immune activation, we examined whether this pathological association involves genome-wide DNA methylation differences at single nucleotide resolution. Prenatal immune activation was induced by maternal treatment with the viral mimetic polyriboinosinic-polyribocytidylic acid in middle or late gestation. Following behavioral and cognitive characterization of the adult offspring (n = 12 per group), unbiased capture array bisulfite sequencing was combined with subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitative real-time polymerase chain reaction analyses to quantify DNA methylation changes and transcriptional abnormalities in the medial prefrontal cortex of immune-challenged and control offspring. Gene ontology term enrichment analysis was used to explore shared functional pathways of genes with differential DNA methylation. Adult offspring of immune-challenged mothers displayed hyper- and hypomethylated CpGs at numerous loci and at distinct genomic regions, including genes relevant for gamma-aminobutyric acidergic differentiation and signaling (e.g., Dlx1, Lhx5, Lhx8), Wnt signaling (Wnt3, Wnt8a, Wnt7b), and neural development (e.g., Efnb3, Mid1, Nlgn1, Nrxn2). Altered DNA methylation was associated with transcriptional changes of the corresponding genes. The epigenetic and transcriptional effects were dependent on the offspring's age and were markedly influenced by the precise timing of prenatal immune activation. Prenatal viral-like immune activation is capable of inducing stable DNA methylation changes in the medial prefrontal cortex. These long-term epigenetic modifications are a plausible mechanism underlying the disruption of prefrontal gene transcription and behavioral functions in subjects with prenatal infectious histories. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

PubMed Central

Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

2015-01-01

Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

In Utero and Postnatal Propylthiouracil-Induced Mild Hypothyroidism Impairs Maternal Behavior in Mice.

PubMed

Khairinisa, Miski Aghnia; Takatsuru, Yusuke; Amano, Izuki; Kokubo, Michifumi; Haijima, Asahi; Miyazaki, Wataru; Koibuchi, Noriyuki

2018-01-01

Thyroid hormones (THs) play crucial roles in general and brain development. Even if the hypothyroidism is mild, it may alter brain function, resulting in irreversible behavioral alterations. Although various behavioral analyses have been conducted, the effects of propylthiouracil (PTU) treatment during in utero and postnatal periods on maternal behavior have not yet been studied. The present study examined in mice whether THs insufficiency during development induce behavioral changes. Pregnant C57BL/6j mice were divided into three groups, and each group was administered different dosages of PTU (0, 5, or 50 ppm) in drinking water during in utero and postnatal periods (from gestational day 14 to postnatal day 21). First, locomotor activity and cognitive function were assessed in the offspring at 10 weeks. Next, female offspring were mated with normal mice and they and their offspring were used to assess several aspects of maternal behavior (identifying first pup, returning all pups to nest, time spent nursing, and licking pups). As expected, locomotor and cognitive functions in these mice were disrupted in a PTU dose-dependent manner. On postpartum day 2, dams who had been exposed 50 ppm PTU during in utero and postnatal periods displayed a significantly longer time identifying the first pup and returning all three pups back to the nest, less time nursing, and decreased licking behavior. The decrease in maternal behavior was significantly correlated with a decrease in cognition. These results indicate that insufficiency of THs during in utero and postnatal periods impairs maternal behavior, which may be partly induced by impaired cognitive function.

Prenatal stress produces anxiety prone female offspring and impaired maternal behaviour in the domestic pig.

PubMed

Rutherford, Kenneth M D; Piastowska-Ciesielska, Agnieszka; Donald, Ramona D; Robson, Sheena K; Ison, Sarah H; Jarvis, Susan; Brunton, Paula J; Russell, John A; Lawrence, Alistair B

2014-04-22

Numerous studies have shown that prenatal stress (PNS) can have profound effects on postnatal well-being. Here, the domestic pig (Sus scrofa) was used to investigate PNS effects owing to the direct relevance for farm animal welfare and the developing status of the pig as a large animal model in translational research. Pregnant primiparous sows were exposed, in mid-gestation, to either a social stressor (mixing with unfamiliar conspecifics) or were kept in stable social groups. The ratio of levels of mRNAs for corticotropin releasing hormone (CRH) receptors 1 and 2 in the amygdala, measured for the first time in the pig, was substantially increased in 10-week-old female, but not male, PNS progeny indicating a neurobiological propensity for anxiety-related behaviour. Mature female offspring were observed at parturition in either a behaviourally restrictive crate or open pen. Such PNS sows showed abnormal maternal behaviour in either environment, following the birth of their first piglet. They spent more time lying ventrally, more time standing and showed a higher frequency of posture changes. They were also more reactive towards their piglets, and spent longer visually attending to their piglets compared to controls. Associated with this abnormal maternal care, piglet mortality was increased in the open pen environment, where protection for piglets is reduced. Overall, these data indicate that PNS females have their brain development shifted towards a pro-anxiety phenotype and that PNS can be causally related to subsequent impaired maternal behaviour in adult female offspring. Copyright © 2014 Elsevier Inc. All rights reserved.

Prenatal exposure to angiotensin II increases blood pressure and decreases salt sensitivity in rats.

PubMed

Svitok, Pavel; Senko, Tomas; Panakova, Zuzana; Olexova, Lucia; Krskova, Lucia; Okuliarova, Monika; Zeman, Michal

2017-01-01

Renin angiotensin aldosterone system (RAAS) plays an essential role in the homeostatic control of arterial blood pressure, perfusion of tissues, and control of extracellular fluid. Its components are highly expressed in the developing kidney, general vasculature, brain, and heart. A modified intrauterine environment alters mechanisms controlling blood pressure (BP) and can lead to hypertension in the adult offspring and developmentally programmed RAAS can be involved in this process. There are very little data about the effects of increased angiotensin II (Ang II) concentrations during pregnancy on in utero development of the fetus. In our study, we administered Ang II to pregnant female rats via osmotic mini-pumps and evaluated the postnatal development and BP control in the offspring. To estimate possible developmental changes in sensitivity to salt, we exposed the offspring to a diet with increased salt content and measured plasma aldosterone levels and plasma renin activity. Increased Ang II during pregnancy raised BP in the offspring; however, salt sensitivity was decreased in comparison to controls. Relative weight of the left ventricle was decreased in the offspring prenatally exposed to Ang II, while relative kidney weight was reduced only in female offspring. Prenatal treatment led to increased aldosterone levels and decreased plasma renin activity, suggesting a complex physiological response. Our results suggest that conditions leading to upregulation of RAAS during pregnancy can influence the cardiovascular system of the fetus and have a long-term impact on the offspring's health.

Reduced Intellectual Ability in Offspring of Ovarian Hyperstimulation Syndrome: A Cohort Study.

PubMed

Xu, Gu-Feng; Zhou, Cheng-Liang; Xiong, Yi-Meng; Li, Jing-Yi; Yu, Tian-Tian; Tian, Shen; Lin, Xian-Hua; Liao, Yun; Lv, Yuan; Zhang, Fang-Hong; Liu, Zhi-Wei; Shi, Yin-Yin; Shen, Yan; Sha, Jin; Zhang, Dan; Zhu, Yi-Min; Sheng, Jian-Zhong; Huang, He-Feng

2017-06-01

Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ=92.7 (14.7), PIQ=108.9 (13.1), FIQ=100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ=100.1 (13.2), PIQ=113.7 (10.8), FIQ=107.4 (11.5)). The prevalence of low IQ (<80) children was 4.7 times higher in OHSS offspring compared with non-OHSS offspring. Maternal estradiol level on hCG administration day was negatively associated with FIQ in offspring. OHSS offspring displayed reduced intellectual ability. Prenatal estradiol exposure might be involved in underlying mechanism. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of parental age and associated size on fecundity, growth and survival in the yellow seahorse Hippocampus kuda.

PubMed

Dzyuba, Borys; Van Look, Katrien J W; Cliffe, Alex; Koldewey, Heather J; Holt, William V

2006-08-01

Seahorses, together with the pipefishes (Family Syngnathidae), are the only vertebrates in which embryonic development takes place within a specialised body compartment, the brood pouch, of the male instead of the female. Embryos develop in close association with the brood pouch epithelium in a manner that bears some resemblance to embryo-placental relationships in mammals. We have explored the hypothesis that parental body size and age should affect offspring postnatal growth and survival if brood pouch quality impacts upon prenatal embryonic nutrition or respiration. Using an aquarium population of the yellow seahorse, Hippocampus kuda, we show here that large parents produce offspring whose initial postnatal growth rates (weeks one to three) were significantly higher than those of the offspring of younger and smaller parents. Whereas 90% of offspring from the larger parents survived for the duration of the study (7 weeks), less that 50% of offspring from smaller parents survived for the same period. For the offspring of large parents, growth rates from individual males were negatively correlated with the number of offspring in the cohort (r=-0.82; P<0.05); this was not the case for offspring from small parents (r=0.048; P>0.9). Observations of embryos within the pouch suggested that when relatively few embryos are present they may attach to functionally advantageous sites and thus gain physiological support during gestation. These results suggest that male body size, and pouch size and function, may influence the future fitness and survival of their offspring.

A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

PubMed

Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

2010-04-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

PubMed Central

Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

2010-01-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort.

PubMed

Grunnet, Louise G; Hansen, Susanne; Hjort, Line; Madsen, Camilla M; Kampmann, Freja B; Thuesen, Anne Cathrine B; Granstrømi, Charlotta; Strøm, Marin; Maslova, Ekaterina; Frikke-Schmidt, Ruth; Damm, Peter; Chavarro, Jorge E; Hu, Frank B; Olsen, Sjurdur F; Vaag, Allan

2017-12-01

Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy. © 2017 by the American Diabetes Association.

A Challenging Issue in the Etiology of Speech Problems: The Effect of Maternal Exposure to Electromagnetic Fields on Speech Problems in the Offspring

PubMed Central

Zarei, S.; Mortazavi, S. M. J.; Mehdizadeh, A. R.; Jalalipour, M.; Borzou, S.; Taeb, S.; Haghani, M.; Mortazavi, S. A. R.; Shojaei-fard, M. B.; Nematollahi, S.; Alighanbari, N.; Jarideh, S.

2015-01-01

Background Nowadays, mothers are continuously exposed to different sources of electromagnetic fields before and even during pregnancy.  It has recently been shown that exposure to mobile phone radiation during pregnancy may lead to adverse effects on the brain development in offspring and cause hyperactivity. Researchers have shown that behavioral problems in laboratory animals which have a similar appearance to ADHD are caused by intrauterine exposure to mobile phones. Objective The purpose of this study was to investigate whether the maternal exposure to different sources of electromagnetic fields affect on the rate and severity of speech problems in their offspring. Methods In this study, mothers of 35 healthy 3-5 year old children (control group) and 77 children and diagnosed with speech problems who had been referred to a speech treatment center in Shiraz, Iran were interviewed. These mothers were asked whether they had exposure to different sources of electromagnetic fields such as mobile phones, mobile base stations, Wi-Fi, cordless phones, laptops and power lines. Results We found a significant association between either the call time (P=0.002) or history of mobile phone use (months used) and speech problems in the offspring (P=0.003). However, other exposures had no effect on the occurrence of speech problems. To the best of our knowledge, this is the first study to investigate a possible association between maternal exposure to electromagnetic field and speech problems in the offspring. Although a major limitation in our study is the relatively small sample size, this study indicates that the maternal exposure to common sources of electromagnetic fields such as mobile phones can affect the occurrence of speech problems in the offspring. PMID:26396971

A Challenging Issue in the Etiology of Speech Problems: The Effect of Maternal Exposure to Electromagnetic Fields on Speech Problems in the Offspring.

PubMed

Zarei, S; Mortazavi, S M J; Mehdizadeh, A R; Jalalipour, M; Borzou, S; Taeb, S; Haghani, M; Mortazavi, S A R; Shojaei-Fard, M B; Nematollahi, S; Alighanbari, N; Jarideh, S

2015-09-01

Nowadays, mothers are continuously exposed to different sources of electromagnetic fields before and even during pregnancy.  It has recently been shown that exposure to mobile phone radiation during pregnancy may lead to adverse effects on the brain development in offspring and cause hyperactivity. Researchers have shown that behavioral problems in laboratory animals which have a similar appearance to ADHD are caused by intrauterine exposure to mobile phones. The purpose of this study was to investigate whether the maternal exposure to different sources of electromagnetic fields affect on the rate and severity of speech problems in their offspring. In this study, mothers of 35 healthy 3-5 year old children (control group) and 77 children and diagnosed with speech problems who had been referred to a speech treatment center in Shiraz, Iran were interviewed. These mothers were asked whether they had exposure to different sources of electromagnetic fields such as mobile phones, mobile base stations, Wi-Fi, cordless phones, laptops and power lines. We found a significant association between either the call time (P=0.002) or history of mobile phone use (months used) and speech problems in the offspring (P=0.003). However, other exposures had no effect on the occurrence of speech problems. To the best of our knowledge, this is the first study to investigate a possible association between maternal exposure to electromagnetic field and speech problems in the offspring. Although a major limitation in our study is the relatively small sample size, this study indicates that the maternal exposure to common sources of electromagnetic fields such as mobile phones can affect the occurrence of speech problems in the offspring.

Resveratrol Intake During Pregnancy and Lactation Modulates the Early Metabolic Effects of Maternal Nutrition Differently in Male and Female Offspring.

PubMed

Ros, Purificación; Díaz, Francisca; Freire-Regatillo, Alejandra; Argente-Arizón, Pilar; Barrios, Vicente; Argente, Jesús; Chowen, Julie A

2018-02-01

Poor maternal nutrition can have detrimental long-term consequences on energy homeostasis in the offspring. Resveratrol exerts antioxidant and antiobesity actions, but its impact during development remains largely unknown. We hypothesized that resveratrol intake during pregnancy and lactation could improve the effects of poor maternal nutrition on offspring metabolism. Wistar rats received a low-fat diet (LFD; 10.2% kcal from fat) or high-fat diet (HFD; 61.6% kcal from fat), with half of each group receiving resveratrol in their drinking water (50 mg/L) during pregnancy and lactation. Body weight (BW) of dams was measured at treatment onset and weaning [postnatal day (PND) 21] and of pups at birth and PND21, at which time dams and pups were euthanized. Although HFD dams consumed more energy, their BW at the end of lactation was unaffected. Mean litter size was not modified by maternal diet or resveratrol. At birth, male offspring from HFD and resveratrol (HFD + R) dams weighed less than those from LFD and resveratrol (LFD + R) dams. On PND21, pups of both sexes from HFD dams weighed more, had more visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT), and had higher serum leptin levels than those from LFD dams. Resveratrol reduced BW, leptin, VAT, and SCAT, with females being more affected, but increased glycemia. Neuropeptide levels were unaffected by resveratrol. In conclusion, resveratrol intake during pregnancy and lactation decreased BW and adipose tissue content in offspring of dams on an HFD but did not affect offspring from LFD-fed dams, suggesting that the potential protective effects of resveratrol during gestation/lactation are diet dependent. Copyright © 2018 Endocrine Society.

Gestational and Lactational Exposure to an Environmentally-Relevant Mixture of Brominated Flame Retardants: Effects on Neurodevelopment and Metabolism.

PubMed

Tung, Emily W Y; Kawata, Alice; Rigden, Marc; Bowers, Wayne J; Caldwell, Don; Holloway, Alison C; Robaire, Bernard; Hales, Barbara F; Wade, Michael G

2017-04-17

Developmental exposure to brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), has been associated with impaired neurodevelopment and some symptoms of metabolic syndrome. However, there are inconsistencies in studies reporting neurodevelopmental effects with studies of pure substances more likely to report effects than studies of technical products. In addition, the influence of early BFR exposures on later development of metabolic disease-like symptoms has not been investigated. This study examined the effects of perinatal exposure to an environmentally relevant mixture of BFRs based on relative levels observed in house dust, on several markers of neurodevelopment and metabolism in offspring. Sprague-Dawley female rats were fed a diet estimated to deliver daily doses of 0, 0.06, 20, or 60 mg/kg of a mixture of PBDEs and HBCDD from before mating to weaning. Offspring were weaned to control diet and subjected to neurobehavioral and metabolic assessments. Exposure to BFRs decreased vertical movement in at postnatal day (PND) 32 and increased time to emerge to a lighted area on PND 105 in offspring of both sexes. Although early life exposure to the BFR mixture did not impact measures of glucose or insulin action, male offspring had significantly decreased fat pad weights at PND 46. Total cholesterol was increased in male and female offspring exposed to the highest dose at PND 21. These results suggest that gestational and lactational exposure to an environmentally relevant BFR mixture may induce changes in neurodevelopment and lipid metabolism in offspring. Birth Defects Research 109:497-512, 2017.© 2017 The Authors Birth Defects Research Published by Wiley Periodicals, Inc. © 2017 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.

Gestational and Lactational Exposure to an Environmentally‐Relevant Mixture of Brominated Flame Retardants: Effects on Neurodevelopment and Metabolism

PubMed Central

Tung, Emily W. Y.; Kawata, Alice; Rigden, Marc; Bowers, Wayne J.; Caldwell, Don; Holloway, Alison C.; Robaire, Bernard; Hales, Barbara F.

2017-01-01

Background Developmental exposure to brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), has been associated with impaired neurodevelopment and some symptoms of metabolic syndrome. However, there are inconsistencies in studies reporting neurodevelopmental effects with studies of pure substances more likely to report effects than studies of technical products. In addition, the influence of early BFR exposures on later development of metabolic disease‐like symptoms has not been investigated. This study examined the effects of perinatal exposure to an environmentally relevant mixture of BFRs based on relative levels observed in house dust, on several markers of neurodevelopment and metabolism in offspring. Methods Sprague–Dawley female rats were fed a diet estimated to deliver daily doses of 0, 0.06, 20, or 60 mg/kg of a mixture of PBDEs and HBCDD from before mating to weaning. Offspring were weaned to control diet and subjected to neurobehavioral and metabolic assessments. Results Exposure to BFRs decreased vertical movement in at postnatal day (PND) 32 and increased time to emerge to a lighted area on PND 105 in offspring of both sexes. Although early life exposure to the BFR mixture did not impact measures of glucose or insulin action, male offspring had significantly decreased fat pad weights at PND 46. Total cholesterol was increased in male and female offspring exposed to the highest dose at PND 21. Conclusions These results suggest that gestational and lactational exposure to an environmentally relevant BFR mixture may induce changes in neurodevelopment and lipid metabolism in offspring. Birth Defects Research 109:497–512, 2017.© 2017 The Authors Birth Defects Research Published by Wiley Periodicals, Inc. PMID:28398660

[Effects of in utero exposure to di(2-ethylhexyl) phthalate on sexual development in female offspring].

PubMed

Ding, Yu; Gao, Yu; Shi, Rong; Zhou, Yi-Jun; Tian, Ying

2010-02-01

To evaluate the ability of di(2-ethylhexyl) phthalate (DEHP) with inducing damage in sexual development of female offspring rats after maternal exposure. On gestational day (GD) 12, pregnant Wistar rats were weighed, encoded and randomly assigned to 5 groups (10 dams per group). From GD 12 through GD 17 each dam was dosed daily by gavage with either corn oil (vehicle control, 1 mgxkg(-1)xd(-1)) or DEHP (1, 250, 750 and 1000 mgxkg(-1)xd(-1)). Then female offspring were monitored for eye opening on postnatal day (PND) 14-17, organ coefficient on PND 22 and the time to vaginal opening on PND 30 - 38 (if vagina did not open during the period, observation time should extent to adult), as well as body weight, time to first estrus. No significant changes were observed on eye opening at any dose, which were (15.8 +/- 0.4) d, (16.3 +/- 0.6) d, (16.0 +/- 0.6) d, (15.9 +/- 0.6) d, (15.8 +/- 0.4) d respectively in control, 1, 250, 750 and 1000 mgxkg(-1)xd(-1) (F = 1.363, P = 0.262). However, 62.50% (15/24), 81.25% (26/32) female offspring were permanently absence of vaginal orifice in 750 and 1000 mgxkg(-1)xd(-1) groups respectively, while control, 1 and 250 mgxkg(-1)xd(-1) groups developed normally with vaginal orifices (chi(2) values were 84.92, 132.79, respectively, P < 0.01). The ages of vaginal opening were (32.7 +/- 1.3) d, (33.3 +/- 1.5) d, (32.2 +/- 1.5) d, (33.1 +/- 1.3) d, (33.3 +/- 1.2) d and the body weight were (91.56 +/- 6.65) g, (93.79 +/- 6.28) g, (92.98 +/- 8.48) g, (100.57 +/- 6.47) g, (103.83 +/- 8.24) g in control, 1, 250, 750 and 1000 mgxkg(-1)xd(-1). After covariance adjustment for body weight, which can statistically influenced the age of vaginal opening (F = 40.857, P < 0.05), difference were found at the age of vaginal opening (F = 3.075, P < 0.05), and 250 mgxkg(-1)xd(-1) group was advanced than control (t = -2.056, P < 0.05). Exposure to DEHP in utero from GD 12 - 17 can result in abnormalities of sexual development such as the time to vaginal opening and vaginal atresia.

Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder

PubMed Central

Karchemskiy, Asya; Garrett, Amy; Howe, Meghan; Adleman, Nancy; Simeonova, Diana I.; Alegria, Dylan; Reiss, Allan; Chang, Kiki

2011-01-01

Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are significantly at high-risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents with (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdala volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD. PMID:22041532

Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder.

PubMed

Karchemskiy, Asya; Garrett, Amy; Howe, Meghan; Adleman, Nancy; Simeonova, Diana I; Alegria, Dylan; Reiss, Allan; Chang, Kiki

2011-12-30

Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD. 2011 Elsevier Ireland Ltd. All rights reserved.

Feeding a diet devoid of choline to lactating rodents restricts growth and lymphocyte development in offspring.

PubMed

Lewis, E D; Goruk, S; Richard, C; Dellschaft, N S; Curtis, J M; Jacobs, R L; Field, C J

2016-09-01

The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague-Dawley dams were randomised to either a choline-devoid (ChD; n 7) or choline-sufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P<0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P<0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P<0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.

Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women’s Survey

PubMed Central

Harvey, Nicholas C.; Moon, Rebecca J.; Sayer, Avan Aihie; Ntani, Georgia; Davies, Justin H.; Javaid, M Kassim; Robinson, Sian M.; Godfrey, Keith M.; Inskip, Hazel M.; Cooper, Cyrus

2013-01-01

Context Maternal 25-hydroxy-vitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function but little is known about a role for antenatal 25(OH)D exposure in programming muscle development. Objective We investigated the associations between maternal plasma 25(OH)D status at 34 weeks gestation and offspring lean mass and muscle strength at 4 years of age. Design and setting A prospective UK population-based mother-offspring cohort: the Southampton Women’s Survey (SWS). Participants 12583 non-pregnant women were initially recruited into SWS, of which 3159 had singleton pregnancies. 678 mother-child pairs were included in this analysis. Main Outcomes Measured At 4 years of age, offspring assessments included hand grip strength (Jamar Dynamometer) and whole body DXA (Hologic Discovery) yielding lean mass and %lean mass. Physical activity was assessed by 7-day accelerometry (Actiheart) in a subset of children (n=326). Results Maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength (β=0.10 SD/SD, p=0.013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding and child’s physical activity at 4 years (β=0.13 SD/SD, p=0.014). Maternal 25(OH)D was also positively associated with offspring %lean mass (β=0.11 SD/SD, p=0.006), but not total lean mass (β=0.06, p=0.15). This however did not persist after adjustment for confounding factors (β=0.09 SD/SD, p=0.11). Conclusions This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than muscle mass. PMID:24178796

Evolution of monogamy, paternal investment, and female life history in Peromyscus.

PubMed

Jašarević, Eldin; Bailey, Drew H; Crossland, Janet P; Dawson, Wallace D; Szalai, Gabor; Ellersieck, Mark R; Rosenfeld, Cheryl S; Geary, David C

2013-02-01

The timing of reproductive development and associated trade-offs in quantity versus quality of offspring produced across the life span are well documented in a wide range of species. The relation of these aspects of maternal life history to monogamy and paternal investment in offspring is not well studied in mammals, due in part to the rarity of the latter. By using five large, captive-bred populations of Peromyscus species that range from promiscuous mating with little paternal investment (P. maniculatus bairdii) to social and genetic monogamy with substantial paternal investment (P. californicus insignis), we modeled the interaction between monogamy and female life history. Monogamy and high paternal investment were associated with smaller litter size, delayed maternal reproduction that extended over a longer reproductive life span, and larger, higher quality offspring. The results suggest monogamy and paternal investment can alter the evolution of female life-history trajectories in mammals. PsycINFO Database Record (c) 2013 APA, all rights reserved

Generation of live offspring from vitrified embryos with synthetic polymers SuperCool X-1000 and SuperCool Z-1000.

PubMed

Marco-Jimenez, F; Jimenez-Trigos, E; Lavara, R; Vicente, J S

2014-01-01

Ice growth and recrystallisation are considered important factors in determining vitrification outcomes. Synthetic polymers inhibit ice formation during cooling or warming of the vitrification process. The aim of this study was to assess the effect of adding commercially available synthetic polymers SuperCool X-1000 and SuperCool Z-1000 to vitrification media on in vivo development competence of rabbit embryos. Four hundred and thirty morphologically normal embryos recovered at 72 h of gestation were used. The vitrification media contained 20% dimethyl sulphoxide and 20% ethylene glycol, either alone or in combination with 1% of SuperCool X-1000 and 1% SuperCool. Our results show that embryos can be successfully vitrified using SuperCool X-1000 and SuperCool Z-1000 and when embryos are transferred, live offspring can be successfully produced. In conclusion, our results demonstrated that we succeeded for the first time in obtaining live offspring after vitrification of embryos using SuperCool X-1000 and SuperCool Z-1000 polymers.

Mothers with gestational diabetes are more likely to give birth to children who experience early weight problems.

PubMed

Hakanen, T; Saha, M T; Salo, M K; Nummi, T; Harjunmaa, U; Lipiäinen, L; Vuorela, N

2016-10-01

We tracked the body mass index (BMI) of children born to mothers with or without gestational diabetes mellitus (GDM) or type 1 diabetes from birth to 12 years of age and examined the trends in both diseases. Antenatal and postnatal health survey data were collected from 6909 Finnish children born at six time points between 1974 and 2004. We compared the BMI trajectory between the offspring of mothers with and without GDM or type 1 diabetes, and the association between GDM and overweight offspring was analysed. The prevalence of GDM and type 1 diabetes increased markedly over the study period. The BMI trajectory in the GDM or type 1 diabetes offspring differed significantly from the nondiabetic offspring. The timing of adiposity rebound occurred significantly earlier in the GDM (4.8 years) and type 1 diabetes (4.4 years) groups than the nondiabetic group (5.5 years). GDM offspring were more likely to be overweight at five, seven and 12 years of age (24.6%, 28.1%, 29.4%) than nondiabetic offspring (15.6%, 18.3%, 18.1%). Children born to mothers with GDM were significantly more likely to be overweight at an early age than those born to nondiabetic mothers. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

PubMed Central

Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

2013-01-01

Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

Cytoplasmic inheritance of parent-offspring cell structure in the clonal diatom Cyclotella meneghiniana.

PubMed

Shirokawa, Yuka; Shimada, Masakazu

2016-11-16

In cytoplasmic inheritance, structural states of a parent cell could be transmitted to offspring cells via two mechanisms. The first is referred to as the hangover of parent structure, where the structure itself remains and faithfully transmits within offspring cells; the second is structural inheritance, wherein the parent structure functions as a template for development of new offspring structure. We estimated to what extent the parent structure affects the development of offspring structure by structural inheritance, using a clone of the diatom Cyclotella meneghiniana The cell has two siliceous valves (a cell wall part at both cell poles): one is inherited from the parent and the other is newly formed. We estimated cytoplasmic heritability by comparing valve traits (central fultoportulae (CTFP), striae, central area, and cell diameter) of parent and new offspring valves, using single-cell isolation and valve labelling. Parent-offspring valve trait regressions showed that all traits, except CTFP, were significantly correlated. We formulated a quantitative genetic model considering the diatom inheritance system and revealed short-term rapid evolution compared with other inheritance systems. Diatom structural inheritance will have evolved to enable clonal populations to rapidly acquire and maintain suitable structures for temporal changes in environments and life-cycle stages. © 2016 The Author(s).

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

Evaluation of offspring and maternal genetic effects on disease risk using a family-based approach: the "pent" design.

PubMed

Mitchell, Laura E; Weinberg, Clarice R

2005-10-01

Diseases that develop during gestation may be influenced by the genotype of the mother and the inherited genotype of the embryo/fetus. However, given the correlation between maternal and offspring genotypes, differentiating between inherited and maternal genetic effects is not straightforward. The two-step transmission disequilibrium test was the first, family-based test proposed for the purpose of differentiating between maternal and offspring genetic effects. However, this approach, which requires data from "pents" comprising an affected child, mother, father, and maternal grandparents, provides biased tests for maternal genetic effects when the offspring genotype is associated with disease. An alternative approach based on transmissions from grandparents provides unbiased tests for maternal and offspring genetic effects but requires genotype information for paternal grandparents in addition to pents. The authors have developed two additional, pent-based approaches for the evaluation of maternal and offspring genetic effects. One approach requires the assumption of genetic mating type symmetry (pent-1), whereas the other does not (pent-2). Simulation studies demonstrate that both of these approaches provide valid estimation and testing for offspring and maternal genotypic effects. In addition, the power of the pent-1 approach is comparable with that of the approach based on data using all four grandparents.

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.

MitoQ supplementation prevent long-term impact of maternal smoking on renal development, oxidative stress and mitochondrial density in male mice offspring.

PubMed

Sukjamnong, Suporn; Chan, Yik Lung; Zakarya, Razia; Nguyen, Long The; Anwer, Ayad G; Zaky, Amgad A; Santiyanont, Rachana; Oliver, Brian G; Goldys, Ewa; Pollock, Carol A; Chen, Hui; Saad, Sonia

2018-04-26

To investigate the effect of maternal MitoQ treatment on renal disorders caused by maternal cigarette smoke exposure (SE). We have demonstrated that maternal SE during pregnancy increases the risk of developing chronic kidney disease (CKD) in adult offspring. Mitochondrial oxidative damage contributes to the adverse effects of maternal smoking on renal disorders. MitoQ is a mitochondria-targeted antioxidant that has been shown to protect against oxidative damage-related pathologies in many diseases. Female Balb/c mice (8 weeks) were divided into Sham (exposed to air), SE (exposed to cigarette smoke) and SEMQ (exposed to cigarette smoke with MitoQ supplemented from mating) groups. Kidneys from the mothers were collected when the pups weaned and those from the offspring were collected at 13 weeks. Maternal MitoQ supplementation during gestation and lactation significantly reversed the adverse impact of maternal SE on offspring's body weight, kidney mass and renal pathology. MitoQ administration also significantly reversed the impact of SE on the renal cellular mitochondrial density and renal total reactive oxygen species in both the mothers and their offspring in adulthood. Our results suggested that MitoQ supplementation can mitigate the adverse impact of maternal SE on offspring's renal pathology, renal oxidative stress and mitochondrial density in mice offspring.

Cortisol in mother's milk across lactation reflects maternal life history and predicts infant temperament.

PubMed

Hinde, Katie; Skibiel, Amy L; Foster, Alison B; Del Rosso, Laura; Mendoza, Sally P; Capitanio, John P

2015-01-01

The maternal environment exerts important influences on offspring mass/growth, metabolism, reproduction, neurobiology, immune function, and behavior among birds, insects, reptiles, fish, and mammals. For mammals, mother's milk is an important physiological pathway for nutrient transfer and glucocorticoid signaling that potentially influences offspring growth and behavioral phenotype. Glucocorticoids in mother's milk have been associated with offspring behavioral phenotype in several mammals, but studies have been handicapped by not simultaneously evaluating milk energy density and yield. This is problematic as milk glucocorticoids and nutrients likely have simultaneous effects on offspring phenotype. We investigated mother's milk and infant temperament and growth in a cohort of rhesus macaque ( Macaca mulatta ) mother-infant dyads at the California National Primate Research Center ( N = 108). Glucocorticoids in mother's milk, independent of available milk energy, predicted a more Nervous, less Confident temperament in both sons and daughters. We additionally found sex differences in the windows of sensitivity and the magnitude of sensitivity to maternal-origin glucocorticoids. Lower parity mothers produced milk with higher cortisol concentrations. Lastly, higher cortisol concentrations in milk were associated with greater infant weight gain across time. Taken together, these results suggest that mothers with fewer somatic resources, even in captivity, may be "programming" through cortisol signaling, behaviorally cautious offspring that prioritize growth. Glucocorticoids ingested through milk may importantly contribute to the assimilation of available milk energy, development of temperament, and orchestrate, in part, the allocation of maternal milk energy between growth and behavioral phenotype.

Financial analysis of various strategies for the control of Neospora caninum in dairy cattle in Switzerland.

PubMed

Häsler, Barbara; Regula, Gertraud; Stärk, Katharina D C; Sager, Heinz; Gottstein, Bruno; Reist, Martin

2006-12-18

The present study was conducted to estimate the direct losses due to Neospora caninum in Swiss dairy cattle and to assess the costs and benefits of different potential control strategies. A Monte Carlo simulation spreadsheet module was developed to estimate the direct costs caused by N. caninum, with and without control strategies, and to estimate the costs of these control strategies in a financial analysis. The control strategies considered were "testing and culling of seropositive female cattle", "discontinued breeding with offspring from seropositive cows", "chemotherapeutical treatment of female offspring" and "vaccination of all female cattle". Each parameter in the module that was considered to be uncertain, was described using probability distributions. The simulations were run with 20,000 iterations over a time period of 25 years. The median annual losses due to N. caninum in the Swiss dairy cow population were estimated to be euro 9.7 million euros. All control strategies that required yearly serological testing of all cattle in the population produced high costs and thus were not financially profitable. Among the other control strategies, two showed benefit-cost ratios (BCR) >1 and positive net present values (NPV): "Discontinued breeding with offspring from seropositive cows" (BCR=1.29, NPV=25 million euros ) and "chemotherapeutical treatment of all female offspring" (BCR=2.95, NPV=59 million euros). In economic terms, the best control strategy currently available would therefore be "discontinued breeding with offspring from seropositive cows".

Cortisol in mother’s milk across lactation reflects maternal life history and predicts infant temperament

PubMed Central

Skibiel, Amy L.; Foster, Alison B.; Del Rosso, Laura; Mendoza, Sally P.; Capitanio, John P.

2015-01-01

The maternal environment exerts important influences on offspring mass/growth, metabolism, reproduction, neurobiology, immune function, and behavior among birds, insects, reptiles, fish, and mammals. For mammals, mother’s milk is an important physiological pathway for nutrient transfer and glucocorticoid signaling that potentially influences offspring growth and behavioral phenotype. Glucocorticoids in mother’s milk have been associated with offspring behavioral phenotype in several mammals, but studies have been handicapped by not simultaneously evaluating milk energy density and yield. This is problematic as milk glucocorticoids and nutrients likely have simultaneous effects on offspring phenotype. We investigated mother’s milk and infant temperament and growth in a cohort of rhesus macaque (Macaca mulatta) mother–infant dyads at the California National Primate Research Center (N = 108). Glucocorticoids in mother’s milk, independent of available milk energy, predicted a more Nervous, less Confident temperament in both sons and daughters. We additionally found sex differences in the windows of sensitivity and the magnitude of sensitivity to maternal-origin glucocorticoids. Lower parity mothers produced milk with higher cortisol concentrations. Lastly, higher cortisol concentrations in milk were associated with greater infant weight gain across time. Taken together, these results suggest that mothers with fewer somatic resources, even in captivity, may be “programming” through cortisol signaling, behaviorally cautious offspring that prioritize growth. Glucocorticoids ingested through milk may importantly contribute to the assimilation of available milk energy, development of temperament, and orchestrate, in part, the allocation of maternal milk energy between growth and behavioral phenotype. PMID:25713475

Effects of environmental enrichment during abstinence in morphine dependent parents on anxiety, depressive-like behaviors and voluntary morphine consumption in rat offspring.

PubMed

Pooriamehr, Alireza; Sabahi, Parviz; Miladi-Gorji, Hossein

2017-08-24

Chronic morphine exposure during puberty increased morphine-induced rewarding effects and sensitization in the next generation. Given the well-known beneficial effects of environmental enrichment on the severity of physical and psychological dependence on morphine, we examined effects of enriched environment during morphine abstinence in morphine dependent parental rats before mating on the anxiety and depressive-like behaviors, and voluntary morphine consumption in their offspring. Paternal and/or maternal rats were injected with bi-daily doses (10mg/kg, 12h intervals) of morphine for 14days followed by rearing in a standard environment (SE) or enriched environment (EE) during 30days of morphine abstinence before mating. The pubertal male and female rat offspring were tested for anxiety (the elevated plus maze- EPM) and depression (sucrose preference test-SPT), and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that EE experience in morphine-dependent both parents result in an increase in the percentage of time spent into open arms/time spent on both arms using EPM in male offspring, higher levels of sucrose preference in female offspring and lower levels of voluntary morphine consumption in male and female offspring. Thus, EE experience in morphine-dependent both parents reduced anxiety, depressive-like behavior and also the voluntary morphine consumption in their offspring during puberty which may prevent the vulnerability of the next generation to drug abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between stressful life events and Axis I diagnoses among adolescent offspring of probands with bipolar and non-bipolar psychiatric disorders and healthy controls

PubMed Central

Pan, Lisa A.; Goldstein, Tina R.; Rooks, Brian T.; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S.; Sakolsky, Dara J.; Hafeman, Daniella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J.; Axelson, David; Brent, David A.; Birmaher, Boris

2018-01-01

Background Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Scale(SLES) among three groups of adolescent offspring of probands: with bipolar(BD), with non-BD psychiatric disorders, and healthy control(HC). Furthermore, we examined the relationship between stressful life events and presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent or independent), and positive, negative, and neutral (neither positive or negative). Method Offspring of probands with BD aged 13–18 years(N=269), demographically-matched offspring of probands with non-BD Axis I disorders(N=88), and HC probands(N=81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002–2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current offspring Axis I diagnoses after adjusting for confounds. Results After adjusting for demographic and clinical between-group differences(in probands and offspring), offspring of BD probands had greater independent and neutral life events compared with HC offspring and greater number of more severe stressful life events than HC offspring, but not non-BD offspring. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events. Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both BD and non-BD affected probands regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Conclusions Offspring of BD probands have greater exposure to independent and neutral life events than HC offspring. Greater frequency and severity of stressful life events was associated with Axis I disorder in offspring of both BD and non-BD affected probands. PMID:28199068

Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons.

PubMed

Le Foll, Christelle; Irani, Boman G; Magnan, Christophe; Dunn-Meynell, Ambrose; Levin, Barry E

2009-11-01

Maternal obesity accentuates offspring obesity in dams bred to develop diet-induced obesity (DIO) on a 31% fat, high-sucrose, high-energy (HE) diet but has no effect on offspring of diet-resistant (DR) dams. Also, only DIO dams become obese when they and DR dams are fed HE diet throughout gestation and lactation. We assessed glucose and oleic acid (OA) sensitivity of dissociated ventromedial hypothalamic nucleus (VMN) neurons from 3- to 4-wk old offspring of DIO and DR dams fed chow or HE diet using fura-2 calcium imaging to monitor intracellular calcium fluctuations as an index of neuronal activity. Offspring of DIO dams fed chow had approximately 2-fold more glucose-inhibited (GI) neurons than did DR offspring. This difference was eliminated in offspring of DIO dams fed HE diet. At 2.5 mM glucose, offspring of chow-fed DIO dams had more GI neurons that were either excited or inhibited by OA than did DR offspring. Maternal HE diet intake generally increased the percentage of neurons that were excited and decreased the percentage that were inhibited by OA in both DIO and DR offspring. However, this effect was more pronounced in DIO offspring. These data, as well as concentration-dependent differences in OA sensitivity, suggest that genotype, maternal obesity, and dietary content can all affect the sensitivity of offspring VMN neurons to glucose and long-chain fatty acids. Such altered sensitivities may underlie the propensity of DIO offspring to become obese when fed high-fat, high-sucrose diets.

Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers.

PubMed

Leveque, Lucie; Hodgson, Samantha; Peyton, Stephen; Koyama, Motoko; MacDonald, Kelli P A; Khosrotehrani, Kiarash

2014-05-01

The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Expression of cerebral serotonin related to anxiety-like behaviors in C57BL/6 offspring induced by repeated subcutaneous prenatal exposure to low-dose lipopolysaccharide

PubMed Central

Hsueh, Pei-Tan; Wang, Hsuan-Han; Liu, Chiu-Lin; Ni, Wei-Fen

2017-01-01

Prenatal exposure to lipopolysaccharide (LPS), which likely occurs due to infection or contact with environmental allergens during pregnancy, is a proposed risk factor that induces anxiety- and autism spectrum disorder-like behaviors in offspring. However, the molecular and behavioral changes in offspring after maternal immune activation have not been completely identified. We hypothesized that a subcutaneous injection of LPS in a pregnant mouse would induce changes in cerebral serotonin (5-HT) in parallel to the appearance of anxiety-like behaviors in the dam’s offspring. After LPS injections (total, 100 μg/Kg), the time spent in the central region during the open field test and the number of times that the mice moved between the light and dark boxes and between the open and closed arms on the elevated plus maze test revealed anxiety-like behaviors in offspring at 5, 6 and 9 weeks of age. The mRNA expression levels of tph2 (5-HT synthesizing enzyme) and slc6a4 (5-HT transporter) were down-regulated in both adolescent (5 weeks of age) and adult (8 weeks of age) brains. Immunohistochemistry revealed that the numbers and sizes of tph2-expressing cells were notably decreased in the raphe nuclei of the midbrain of adults. Moreover, compared with controls (phosphate-buffered saline-treated offspring), the cerebral 5-HT concentration at adolescence and adulthood in LPS-induced offspring was significantly decreased. We concluded that maternal immune activation induced by exposure to a low dose of LPS decreased cerebral 5-HT levels in parallel to the down-regulation of the tph2 and slc6a4 genes and in conjunction with anxiety-like behaviors in offspring. PMID:28650979

A developmental approach to dimensional expression of psychopathology in child and adolescent offspring of parents with bipolar disorder.

PubMed

Morón-Nozaleda, María Goretti; Díaz-Caneja, Covadonga M; Rodríguez-Toscano, Elisa; Arango, Celso; Castro-Fornieles, Josefina; de la Serna, Elena; Espliego, Ana; Sanchez-Gistau, Vanessa; Romero, Soledad; Baeza, Immaculada; Sugranyes, Gisela; Moreno, Carmen; Moreno, Dolores

2017-10-01

The aim of this is to describe psychopathology, functioning and symptom dimensions accounting for subthreshold manifestations and developmental status in child and adolescent offspring of parents with bipolar disorder ("high-risk offspring"). The study population comprised 90 high-risk offspring (HR-offspring) and 107 offspring of community control parents (CC-offspring). Direct clinical observations and parental and offspring reports based on selected standardized clinical scales were used to assess offspring threshold and subthreshold diagnoses, symptoms and functioning. All outcomes were compared between the whole HR-offspring and CC-offspring samples and then by developmental status. After controlling for potential confounders, HR-offspring showed significantly poorer adjustment for childhood (r = 0.18, p = 0.014) and adolescence (r = 0.21, p = 0.048) than CC-offspring, as well as more emotional problems (r = 0.24, p = 0.001) and higher depression scores (r = 0.16, p = 0.021). As for differences in lifetime categorical diagnoses (threshold and subthreshold) between HR-offspring and CC-offspring, the prevalence of disruptive disorders was higher in pre-pubertal HR-offspring (OR 12.78 [1.45-112.42]), while prevalence of mood disorders was higher in post-pubertal HR-offspring (OR 3.39 [1.14-10.06]). Post-pubertal HR-offspring presented more prodromal (r = 0.40, p = 0.001), negative (r = 0.38, p = 0.002), manic (r = 0.22, p = 0.035) and depressive (r = 0.23, p = 0.015) symptoms than pre-pubertal HR-offspring, as well as more peer relationship problems (r = 0.31, p = 0.004), poorer childhood adjustment (r = 0.22, p = 0.044) and worse current psychosocial functioning (r = 0.27, p = 0.04). Externalizing psychopathology is more prevalent in pre-pubertal HR-offspring, while depressive and prodromal symptoms leading to functional impairment are more prominent in post-pubertal HR-offspring. Developmental approaches and dimensional measures may be useful for identifying children at high risk of developing bipolar disorder and help guide specific preventive strategies.

The Relationship Between Stressful Life Events and Axis I Diagnoses Among Adolescent Offspring of Probands With Bipolar and Non-Bipolar Psychiatric Disorders and Healthy Controls: The Pittsburgh Bipolar Offspring Study (BIOS).

PubMed

Pan, Lisa A; Goldstein, Tina R; Rooks, Brian T; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S; Sakolsky, Dara J; Hafeman, Danella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J; Axelson, David A; Brent, David A; Birmaher, Boris

2017-03-01

Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Schedule (SLES) among 3 groups of adolescent offspring of probands with bipolar (BD), with non-BD psychiatric disorders, and healthy controls. Furthermore, we examined the relationship between stressful life events and the presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent nor independent) and positive, negative, or neutral (neither positive nor negative). Offspring of probands with BD aged 13-18 years (n = 269), demographically matched offspring of probands with non-BD Axis I disorders (n = 88), and offspring of healthy controls (n = 81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002 to 2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current Axis I diagnoses in offspring after adjusting for confounds. After adjusting for demographic and clinical between-group differences (in probands and offspring), offspring of probands with BD had greater independent (χ² = 11.96, P < .04) and neutral (χ² = 17.99, P < .003) life events compared with offspring of healthy controls and greater number of more severe stressful life events than offspring of healthy controls, but not offspring of probands with non-BD. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events compared to those without comorbid substance use disorder (P = .024). Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both probands with BD and probands with other Axis I disorders regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Offspring of probands with BD have greater exposure to independent and neutral life events than offspring of healthy controls. Greater frequency and severity of stressful life events were associated with Axis I disorder in offspring of both BD and non-BD affected probands. © Copyright 2017 Physicians Postgraduate Press, Inc.

Lower Maternal Folate Status in Early Pregnancy Is Associated with Childhood Hyperactivity and Peer Problems in Offspring

ERIC Educational Resources Information Center

Schlotz, Wolff; Jones, Alexander; Phillips, David I. W.; Gale, Catharine R.; Robinson, Sian M.; Godfrey, Keith M.

2010-01-01

Background: Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring. Methods: In a prospective cohort study, maternal red…

Cognitively normal individuals with AD parents may be at risk for developing aging-related cortical thinning patterns characteristic of AD.

PubMed

Reiter, Katherine; Alpert, Kathryn I; Cobia, Derin J; Kwasny, Mary J; Morris, John C; Csernansky, John C; Wang, Lei

2012-07-02

Children of Alzheimer's disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p<0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female. Copyright © 2012 Elsevier Inc. All rights reserved.

COGNITIVELY NORMAL INDIVIDUALS WITH AD PARENTS MAY BE AT RISK FOR DEVELOPING AGING-RELATED CORTICAL THINNING PATTERNS CHARACTERISTIC OF AD

PubMed Central

Reiter, Katherine; Alpert, Kathryn I.; Cobia, Derin J.; Kwasny, Mary J.; Morris, John C.; Csernansky, John C.; Wang, Lei

2012-01-01

Children of Alzheimer's Disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p < 0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female. PMID:22503937

Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail

PubMed Central

Zimmer, Cédric; Larriva, Maria; Boogert, Neeltje J.; Spencer, Karen A.

2017-01-01

An interesting aspect of developmental programming is the existence of transgenerational effects that influence offspring characteristics and performance later in life. These transgenerational effects have been hypothesized to allow individuals to cope better with predictable environmental fluctuations and thus facilitate adaptation to changing environments. Here, we test for the first time how early-life stress drives developmental programming and transgenerational effects of maternal exposure to early-life stress on several phenotypic traits in their offspring in a functionally relevant context using a fully factorial design. We manipulated pre- and/or post-natal stress in both Japanese quail mothers and offspring and examined the consequences for several stress-related traits in the offspring generation. We show that pre-natal stress experienced by the mother did not simply affect offspring phenotype but resulted in the inheritance of the same stress-coping traits in the offspring across all phenotypic levels that we investigated, shaping neuroendocrine, physiological and behavioural traits. This may serve mothers to better prepare their offspring to cope with later environments where the same stressors are experienced. PMID:28387355

Enduring Effects of Paternal Deprivation in California Mice (Peromyscus californicus): Behavioral Dysfunction and Sex-Dependent Alterations in Hippocampal New Cell Survival

PubMed Central

Glasper, Erica R.; Hyer, Molly M.; Hunter, Terrence J.

2018-01-01

Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus). California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1) biparental care: mate pairs remained with their offspring until weaning; or (2) paternal deprivation (PD): paternal males were permanently removed from their home cage on postnatal day (PND) 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stress-coping behaviors (i.e., percent time spent immobile) during the forced swim task—an effect that was also not sex-dependent. Together, these findings demonstrate that, in a species where paternal care is not only important for offspring survival, PD can also contribute to altered structural and functional neuroplasticity of the hippocampus. The mechanisms contributing to the observed sex-dependent alterations in new cell survival in the dentate gyrus should be further investigated. PMID:29487509

Synergy of nature and nurture in the development of childhood obesity.

PubMed

Levin, B E

2009-04-01

Epidemiological studies suggest that maternal undernutrition, obesity and diabetes during gestation and lactation can all produce obesity in human offspring. Animal models provide a means of assessing the independent consequences of altering the pre- vs postnatal environments on a variety of metabolic, physiological and neuroendocrine functions, which lead to the development of offspring obesity, diabetes, hypertension and hyperlipidemia. During the gestational period, maternal malnutrition, obesity, type 1 and type 2 diabetes, and psychological and pharmacological stressors can all promote offspring obesity. Normal postnatal nutrition can sometimes reduce the adverse effect of some of these prenatal factors, but may also exacerbate the development of obesity and diabetes in offspring of dams that are malnourished during gestation. The genetic background of the individual is also an important determinant of outcome when the perinatal environment is perturbed. Individuals with an obesity-prone genotype are more likely to be adversely affected by factors such as maternal obesity and high-fat diets. Many perinatal manipulations are associated with reorganization of the central neural pathways which regulate food intake, energy expenditure and storage in ways that enhance the development of obesity and diabetes in offspring. Both leptin and insulin have strong neurotrophic properties so that an excess or an absence of either of them during the perinatal period may underlie some of these adverse developmental changes. As perinatal manipulations can permanently and adversely alter the systems that regulate energy homeostasis, it behooves us to gain a better understanding of the factors during this period that promote the development of offspring obesity as a means of stemming the tide of the emerging worldwide obesity epidemic.

Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.

PubMed

Rayen, Ine; van den Hove, Daniël L; Prickaerts, Jos; Steinbusch, Harry W; Pawluski, Jodi L

2011-01-01

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.

Parental prey selection affects risk-taking behaviour and spatial learning in avian offspring

PubMed Central

Arnold, Kathryn E; Ramsay, Scot L; Donaldson, Christine; Adam, Aileen

2007-01-01

Early nutrition shapes life history. Parents should, therefore, provide a diet that will optimize the nutrient intake of their offspring. In a number of passerines, there is an often observed, but unexplained, peak in spider provisioning during chick development. We show that the proportion of spiders in the diet of nestling blue tits, Cyanistes caeruleus, varies significantly with the age of chicks but is unrelated to the timing of breeding or spider availability. Moreover, this parental prey selection supplies nestlings with high levels of taurine particularly at younger ages. This amino acid is known to be both vital and limiting for mammalian development and consequently found in high concentrations in placenta and milk. Based on the known roles of taurine in mammalian brain development and function, we then asked whether by supplying taurine-rich spiders, avian parents influence the stress responsiveness and cognitive function of their offspring. To test this, we provided wild blue tit nestlings with either a taurine supplement or control treatment once daily from the ages of 2–14 days. Then pairs of size- and sex-matched siblings were brought into captivity for behavioural testing. We found that juveniles that had received additional taurine as neonates took significantly greater risks when investigating novel objects than controls. Taurine birds were also more successful at a spatial learning task than controls. Additionally, those individuals that succeeded at a spatial learning task had shown intermediate levels of risk taking. Non-learners were generally very risk-averse controls. Early diet therefore has downstream impacts on behavioural characteristics that could affect fitness via foraging and competitive performance. Fine-scale prey selection is a mechanism by which parents can manipulate the behavioural phenotype of offspring. PMID:17698490

Parental prey selection affects risk-taking behaviour and spatial learning in avian offspring.

PubMed

Arnold, Kathryn E; Ramsay, Scot L; Donaldson, Christine; Adam, Aileen

2007-10-22

Early nutrition shapes life history. Parents should, therefore, provide a diet that will optimize the nutrient intake of their offspring. In a number of passerines, there is an often observed, but unexplained, peak in spider provisioning during chick development. We show that the proportion of spiders in the diet of nestling blue tits, Cyanistes caeruleus, varies significantly with the age of chicks but is unrelated to the timing of breeding or spider availability. Moreover, this parental prey selection supplies nestlings with high levels of taurine particularly at younger ages. This amino acid is known to be both vital and limiting for mammalian development and consequently found in high concentrations in placenta and milk. Based on the known roles of taurine in mammalian brain development and function, we then asked whether by supplying taurine-rich spiders, avian parents influence the stress responsiveness and cognitive function of their offspring. To test this, we provided wild blue tit nestlings with either a taurine supplement or control treatment once daily from the ages of 2-14 days. Then pairs of size- and sex-matched siblings were brought into captivity for behavioural testing. We found that juveniles that had received additional taurine as neonates took significantly greater risks when investigating novel objects than controls. Taurine birds were also more successful at a spatial learning task than controls. Additionally, those individuals that succeeded at a spatial learning task had shown intermediate levels of risk taking. Non-learners were generally very risk-averse controls. Early diet therefore has downstream impacts on behavioural characteristics that could affect fitness via foraging and competitive performance. Fine-scale prey selection is a mechanism by which parents can manipulate the behavioural phenotype of offspring.

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.

The subtle intracapsular survival of the fittest: maternal investment, sibling conflict, or environmental effects?

PubMed

Smith, Kathryn E; Thatje, Sven

2013-10-01

Developmental resource partitioning and the consequent offspring size variations are of fundamental importance for marine invertebrates, in both an ecological and evolutionary context. Typically, differences are attributed to maternal investment and the environmental factors determining this; additional variables, such as environmental factors affecting development, are rarely discussed. During intracapsular development, for example, sibling conflict has the potential to affect resource partitioning. Here, we investigate encapsulated development in the marine gastropod Buccinum undatum. We examine the effects of maternal investment and temperature on intracapsular resource partitioning in this species. Reproductive output was positively influenced by maternal investment, but additionally, temperature and sibling conflict significantly affected offspring size, number, and quality during development. Increased temperature led to reduced offspring number, and a combination of high sibling competition and asynchronous early development resulted in a common occurrence of "empty" embryos, which received no nutrition at all. The proportion of empty embryos increased with both temperature and capsule size. Additionally, a novel example ofa risk in sibling conflict was observed; embryos cannibalized by others during early development ingested nurse eggs from inside the consumer, killing it in a "Trojan horse" scenario. Our results highlight the complexity surrounding offspring fitness. Encapsulation should be considered as significant in determining maternal output. Considering predicted increases in ocean temperatures, this may impact offspring quality and consequently species distribution and abundance.

'Green incubation': avian offspring benefit from aromatic nest herbs through improved parental incubation behaviour.

PubMed

Gwinner, Helga; Capilla-Lasheras, Pablo; Cooper, Caren; Helm, Barbara

2018-06-13

Development of avian embryos requires thermal energy, usually from parents. Parents may, however, trade off catering for embryonic requirements against their own need to forage through intermittent incubation. This dynamically adjusted behaviour can be affected by properties of the nest. Here, we experimentally show a novel mechanism by which parents, through incorporation of aromatic herbs into nests, effectively modify their incubation behaviour to the benefit of their offspring. Our study species, the European starling, includes in its nest aromatic herbs which promote offspring fitness. We provided wild starlings with artificial nests including or excluding the typically selected fresh herbs and found strong support for our prediction of facilitated incubation. Herb effects were not explained by thermal changes of the nests per se , but by modified parental behaviours. Egg temperatures and nest attendance were higher in herb than herbless nests, egg temperatures dropped less frequently below critical thresholds and parents started their active day earlier. These effects were dynamic over time and particularly strong during early incubation. Incubation period was shorter in herb nests, and nestlings were heavier one week after hatching. Aromatic herbs hence influenced incubation in beneficial ways for offspring, possibly through pharmacological effects on incubating parents. © 2018 The Author(s).

Late pregnancy is vulnerable period for exposure to BPA.

PubMed

Ohtani, Naoko; Suda, Koshi; Tsuji, Erika; Tanemura, Kentaro; Yokota, Hiroshi; Inoue, Hiroki; Iwano, Hidetomo

2018-03-30

Bisphenol A (BPA) is among the better-known endocrine disruptors. BPA is used in various food-contacting materials and is easily eluted into food; as a result, we are exposed to BPA on a daily basis. In adults, BPA is metabolized and eliminated rapidly from the body. However, numerous reports suggest that fetuses and young children are susceptible to BPA. One of the concerning adverse effects of BPA is disruption of behavior, especially anxiety-like behavior. In order to study the mechanism of influences on offspring, it is important to clarify the most vulnerable gestation period. We hypothesized that offspring in late pregnancy would be more susceptible to BPA, because late pregnancy is a critical time for functional brain development. In this study, C57BL/6 mouse fetuses were exposed prenatally by oral dosing of pregnant dams, once daily from gestational day 5.5 to 12.5 (early pregnancy) or 11.5 to 18.5 (late pregnancy), with BPA (0 or 10 mg/kg body weight). Following birth and weaning, the resulting pups were tested using an elevated plus maze at postnatal week 10. The behavior of the offspring was altered by prenatal BPA exposure during late pregnancy but not during early pregnancy. These results indicated that offspring are more vulnerable to exposure to BPA in late pregnancy.

Emergence of delayed behavioral effects in offspring mice exposed to low levels of mercury vapor during the lactation period.

PubMed

Yoshida, Minoru; Watanabe, Chiho; Honda, Akiko; Satoh, Masahiko; Yasutake, Akira

2013-02-01

This study examined the emergence of delayed behavioral effects in offspring mice exposed to low levels of mercury vapor (Hg(0)) during the lactation period. Female offspring of mice were repeatedly exposed to Hg(0) at 0.057 mg/m(3), similar to the current threshold value (TLV), for 24 hr until the 20(th) day postpartum. The behavioral effects were evaluated with locomotor activity in the open field (OPF), learning activity in the passive avoidance response (PA) and spatial learning ability in the Morris water maze (MM) at the ages of 3 and 15 months. Hg(0)-exposed mice did not differ from controls in the three behavioral measurements at 3 months of age, and no neurobehavioral effects were observed. On the other hand, the mice exhibited significantly more central locomotion in the OPF task when tested at 15 months of age, but no abnormality in other behavioral performance. Immediately after postnatal exposure, the brain mercury concentration of offspring was about 150 times that of the control, in which the concentrations were approximately 0.4 µg/g. The results indicate that mice exposed to Hg(0) at concentrations around TLV during the developing period resulted in the emergence of delayed behavioral effects at a later stage in life.

Genetic variation of transgenerational plasticity of offspring germination in response to salinity stress and the seed transcriptome of Medicago truncatula.

PubMed

Vu, Wendy T; Chang, Peter L; Moriuchi, Ken S; Friesen, Maren L

2015-04-01

Transgenerational plasticity provides phenotypic variation that contributes to adaptation. For plants, the timing of seed germination is critical for offspring survival in stressful environments, as germination timing can alter the environmental conditions a seedling experiences. Stored seed transcripts are important determinants of seed germination, but have not previously been linked with transgenerational plasticity of germination behavior. In this study we used RNAseq and growth chamber experiments of the model legume M. trucantula to test whether parental exposure to salinity stress influences the expression of stored seed transcripts and early offspring traits and test for genetic variation. We detected genotype-dependent parental environmental effects (transgenerational plasticity) on the expression levels of stored seed transcripts, seed size, and germination behavior of four M. truncatula genotypes. More than 50% of the transcripts detected in the mature, ungerminated seed transcriptome were annotated as regulating seed germination, some of which are involved in abiotic stress response and post-embryonic development. Some genotypes showed increased seed size in response to parental exposure to salinity stress, but no parental environmental influence on germination timing. In contrast, other genotypes showed no seed size differences across contrasting parental conditions but displayed transgenerational plasticity for germimation timing, with significantly delayed germination in saline conditions when parental plants were exposed to salinity. In genotypes that show significant transgenerational plastic germination response, we found significant coexpression networks derived from salt responsive transcripts involved in post-transcriptional regulation of the germination pathway. Consistent with the delayed germination response to saline conditions in these genotypes, we found genes associated with dormancy and up-regulation of abscisic acid (ABA). Our results demonstrate genetic variation in transgenerational plasticity within M. truncatula and show that parental exposure to salinity stress influences the expression of stored seed transcripts, seed weight, and germination behavior. Furthermore, we show that the parental environment influences gene expression to modulate biological pathways that are likely responsible for offspring germination responses to salinity stress.

The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

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

McInturf, S.M.; Bekkedal, M.Y.V.; Wilfong, E.

2011-07-15

The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distressmore » vocalizations were elevated in F{sub 1} offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F{sub 1} females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P{sub 0} animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.« less

Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.

PubMed

Bauman, M D; Iosif, A-M; Ashwood, P; Braunschweig, D; Lee, A; Schumann, C M; Van de Water, J; Amaral, D G

2013-07-09

Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.

Strategies for Establishing a Rearing Technique for the Fruit Fly Parasitoid: Doryctobracon brasiliensis (Hymenoptera: Braconidae).

PubMed

Poncio, S; Nunes, A M; Gonçalves, R D S; Lisboa, H; Manica-Berto, R; Garcia, M S; Nava, D E

2018-05-28

Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae) is the most important pest in South American orchards. When control measures are not adopted, this pest can cause losses of up to 100%. Doryctobracon brasiliensis (Szépligeti) (Hymenoptera: Braconidae) is a larval-pupal endoparasitoid that can be used as a native biological control agent against A. fraterculus. This study aimed to develop a rearing technique for D. brasiliensis in larvae of A. fraterculus. Trials were carried out to: 1) determine the optimal instar for parasitism, 2) define the exposure time of larvae to parasitoids, 3) determine the density requirements of A. fraterculus larvae offered to each parasitoid, and 4) evaluate the effect of diet on adults of D. brasiliensis. In all trials, we evaluated the number of offspring, parasitism rate, and sex ratio. Moreover, in the experiment to investigate the effects of diet, we determined the longevity of males and females. In both choice and nonchoice parasitism tests, the parasitoids preferred third-instar larvae of A. fraterculus over second- and first-instar larvae. An exposure time of 12 h of A. fraterculus larvae produced larger numbers of parasitoids and higher parasitism rates. The density of 15 larvae of A. fraterculus to each female of D. brasiliensis produced a larger number of offspring. A supply of honey solution (20 and 50%) to the parasitoids yielded the highest number offspring and resulted in greater longevity. Our findings can be used to support the development of a mass rearing protocol for D. brasiliensis.

Developmental and neurobehavioral effects of perinatal exposure to diets with different omega-6:omega-3 ratios in mice.

PubMed

Santillán, María E; Vincenti, Laura M; Martini, Ana C; de Cuneo, Marta Fiol; Ruiz, Rubén D; Mangeaud, Arnaldo; Stutz, Graciela

2010-04-01

To investigate in mice the effect of diets enriched with soy or sunflower oil with different omega-6:omega-3 ratios on gestation, reproductive success, physical maturation, and the neurobiological development of the pups. Dams were assigned, throughout gestation and lactation, to different groups: a commercial diet (CD), a soy oil-enriched diet (SOD), or a sunflower oil-enriched diet (SFOD). Measurements during gestation were dams' body weights and daily food intakes. Measurements in the offspring were physical parameters (body weight, body length, body mass index, fur appearance, pinna detachment, incisor eruption, eye opening, and puberty onset) and behavioral preweaning tests (surface righting reflex, negative geotaxis, and cliff avoidance). The SOD and SFOD dams became significantly heavier than the CD dams from gestational days 14 and 19, respectively, to parturition. There were no significant differences in gestational length or food consumption during pregnancy or lactation or in maternal weight during lactation. Diets did not modify litter size, sex ratio, survival index at weaning, or body weight. The SFOD and SOD offspring were significantly shorter than the CD offspring at weaning. The mean offspring physical scores of SOD and SFOD offspring were higher than CD offspring and simple reflexes were earlier in the SOD and SFOD groups. In SFOD offspring, puberty onset was significantly delayed, at postnatal days 26 and 27 in male and female offspring, respectively. This study suggests that the maintenance of an adequate omega-6:omega-3 ratio is necessary for the optimal growth and development of murine offspring. In populations that do not have sufficient provision of polyunsaturated fatty acids in the diet, their consumption would be advisable during gestation and lactation because these improve most neurodevelopmental outcomes included in this study. Copyright 2010 Elsevier Inc. All rights reserved.

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.

Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

PubMed

Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

2014-02-01

Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non-First Nations Offspring.

PubMed

Sellers, Elizabeth A C; Dean, Heather J; Shafer, Leigh Anne; Martens, Patricia J; Phillips-Beck, Wanda; Heaman, Maureen; Prior, Heather J; Dart, Allison B; McGavock, Jonathan; Morris, Margaret; Torshizi, Ali A; Ludwig, Sora; Shen, Garry X

2016-12-01

Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44-3.76; P < 0.0001] vs. 4.86 [95% CI 4.08-5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring. © 2016 by the American Diabetes Association.

Maternal smoking during pregnancy and self-reported delinquency by offspring.

PubMed

Ellis, Lee; Widmayer, Alan; Das, Shyamal

2012-12-01

Several studies have reported significant positive correlations between smoking during pregnancy by mothers and the involvement of their offspring in criminal/delinquent behaviour later in life, but these findings have been described as modest and the criminality based on official conviction statistics. We sought to verify this relationship and probe for more details on the basis of self-reported offending among college students. Independently completed questionnaires were collected from 6332 students and their mothers. The students provided information about their delinquent acts, if any, according to eight categories. Their mothers provided retrospective reports of their smoking habits, if any, during pregnancy. Mothers who recalled having smoked during pregnancy were significantly more likely than non-smoking mothers to have offspring who self-reported engaging in some types of delinquency. This relationship was more evident for female offspring than for male offspring and was most pronounced for illegal drug use by the offspring. There was, however, no relationship between offspring offending and estimated number of cigarettes smoked by mothers, month of pregnancy when smoked or consistency of smoking throughout pregnancy. Overall, our study confirms that maternal smoking during pregnancy is associated with offspring involvement in delinquency, but the lack of critical timing or dose-response relationships between maternal smoking and later offspring delinquency cast doubt on the possibility that the associations are due to teratogenic effects of tobacco smoke. Copyright © 2012 John Wiley & Sons, Ltd.

Familial pathways to early-onset suicide attempt: a 5.6-year prospective study.

PubMed

Brent, David A; Melhem, Nadine M; Oquendo, Maria; Burke, Ainsley; Birmaher, Boris; Stanley, Barbara; Biernesser, Candice; Keilp, John; Kolko, David; Ellis, Steve; Porta, Giovanna; Zelazny, Jamie; Iyengar, Satish; Mann, J John

2015-02-01

Suicide attempts are strong predictors of suicide, a leading cause of adolescent mortality. Suicide attempts are highly familial, although the mechanisms of familial transmission are not understood. Better delineation of these mechanisms could help frame potential targets for prevention. To examine the mechanisms and pathways by which suicidal behavior is transmitted from parent to child. In this prospective study conducted from July 15, 1997, through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age, 17.7 years) of 334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a suicide attempt, were followed up for a mean of 5.6 years. The primary outcome was a suicide attempt. Variables were examined at baseline, intermediate time points, and the time point proximal to the attempt. Participants were assessed by structured psychiatric assessments and self-report and by interview measures of domains hypothesized to be related to familial transmission (eg, mood disorder and impulsive aggression). Among the 701 offspring, 44 (6.3%) had made a suicide attempt before participating in the study, and 29 (4.1%) made an attempt during study follow-up. Multivariate logistic regression revealed that proband suicide attempt was a predictor of offspring suicide attempt (odds ratio [OR], 4.79; 95% CI, 1.75-13.07), even controlling for other salient offspring variables: baseline history of mood disorder (OR, 4.20; 95% CI, 1.37-12.86), baseline history of suicide attempt (OR, 5.69; 95% CI, 1.94-16.74), and mood disorder at the time point before the attempt (OR, 11.32; 95% CI, 2.29-56.00). Path analyses were consistent with these findings, revealing a direct effect of proband attempt on offspring suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive aggression as a precursor of mood disorder. Parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting for the familial transmission of mood disorder. Interventions that target mood disorder and impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal behavior.

Familial Pathways to Early-Onset Suicide Attempt

PubMed Central

Brent, David A.; Melhem, Nadine M.; Oquendo, Maria; Burke, Ainsley; Birmaher, Boris; Stanley, Barbara; Biernesser, Candice; Keilp, John; Kolko, David; Ellis, Steve; Porta, Giovanna; Zelazny, Jamie; Iyengar, Satish; Mann, J. John

2015-01-01

IMPORTANCE Suicide attempts are strong predictors of suicide, a leading cause of adolescent mortality. Suicide attempts are highly familial, although the mechanisms of familial transmission are not understood. Better delineation of these mechanisms could help frame potential targets for prevention. OBJECTIVE To examine the mechanisms and pathways by which suicidal behavior is transmitted from parent to child. DESIGN, SETTING, AND PARTICIPANTS In this prospective study conducted from July 15, 1997, through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age, 17.7 years) of 334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a suicide attempt, were followed up for a mean of 5.6 years. MAIN OUTCOMES AND MEASURES The primary outcome was a suicide attempt. Variables were examined at baseline, intermediate time points, and the time point proximal to the attempt. Participants were assessed by structured psychiatric assessments and self-report and by interview measures of domains hypothesized to be related to familial transmission (eg, mood disorder and impulsive aggression). RESULTS Among the 701 offspring, 44 (6.3%) had made a suicide attempt before participating in the study, and 29 (4.1%) made an attempt during study follow-up. Multivariate logistic regression revealed that proband suicide attempt was a predictor of offspring suicide attempt (odds ratio [OR], 4.79; 95% CI, 1.75–13.07), even controlling for other salient offspring variables: baseline history of mood disorder (OR, 4.20; 95% CI, 1.37–12.86), baseline history of suicide attempt (OR, 5.69; 95% CI, 1.94–16.74), and mood disorder at the time point before the attempt (OR, 11.32; 95% CI, 2.29–56.00). Path analyses were consistent with these findings, revealing a direct effect of proband attempt on offspring suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive aggression as a precursor of mood disorder. CONCLUSIONS AND RELEVANCE Parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting for the familial transmission of mood disorder. Interventions that target mood disorder and impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal behavior. PMID:25548996

Is there a link between biological parents' insight into their offspring's schizophrenia and their cognitive functioning, expressed emotion and knowledge about disorder?

PubMed

Macgregor, Alexandra; Norton, Joanna; Raffard, Stéphane; Capdevielle, Delphine

2017-07-01

Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. Data were drawn from 41 patient-parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of in utero and lactational exposure to SbV on rat neurobehavioral development and fertility.

PubMed

Coelho, Deise R; De-Carvalho, Rosangela R; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Paumgartten, Francisco J R

2014-12-01

Meglumine antimoniate (MA) is a pentavalent antimony drug used to treat leishmaniases. We investigated the neurobehavioral development, sexual maturation and fertility of the offspring of MA-treated rats. Dams were administered MA (0, 75, 150, 300 mg Sb(V)/kg body wt/d, sc) from gestation day 0, throughout parturition and lactation, until weaning. At the highest dose, MA reduced the birth weight and the number of viable newborns. In the male offspring, MA did not impair development (somatic, reflex maturation, weight gain, puberty onset, open field test), sperm count, or reproductive performance. Except for a minor effect on body weight gain and vertical exploration in the open field, MA also did not affect the development of female offspring. Measurements of the Sb levels (ICP-MS) in the blood of MA-treated female rats and their offspring demonstrated that Sb is transferred to the fetuses via the placenta and to the suckling pups via milk. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

ERIC Educational Resources Information Center

Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

2011-01-01

Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring

USDA-ARS?s Scientific Manuscript database

The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosi...

Low offspring survival in mountain pine beetle infesting the resistant Great Basin bristlecone pine supports the preference-performance hypothesis

Treesearch

Erika L. Eidson; Karen E. Mock; Barbara J. Bentz

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...

Perinatal maternal stress and serotonin signaling: effects on pain sensitivity in offspring.

PubMed

Knaepen, Liesbeth; Pawluski, Jodi L; Patijn, Jacob; van Kleef, Maarten; Tibboel, Dick; Joosten, Elbert A

2014-07-01

It has been estimated that 20% of pregnant women are facing perinatal stress and depression. Perinatal maternal stress has been shown to increase pain sensitivity in offspring. For the treatment of their depressive symptoms, pregnant women are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). Since the descending pain inhibitory circuit matures perinatally, perinatal SSRI exposure has been shown to affect pain sensitivity in offspring. In the present review, we summarize experimental and clinical evidence for the effect of perinatal maternal stress and SSRI exposure on pain sensitivity in offspring. Both experimental and clinical studies show the effect of perinatal maternal stress on regulation of the hypothalamic-pituitary-adrenal (HPA) system and the serotonin pain inhibitory system. Alterations in these two systems likely underlie long-term alterations in the development of pain sensitivity. This review sheds light on the effect of perinatal maternal stress and treatment with SSRIs on offspring pain sensitivity, in relation to the developing HPA system and 5-HT signaling. © 2013 Wiley Periodicals, Inc.

Maternal stress during pregnancy increases neonatal allergy susceptibility: role of glucocorticoids.

PubMed

Lim, Robert; Fedulov, Alexey V; Kobzik, Lester

2014-07-15

We sought to test experimentally whether maternal stress can promote susceptibility to development of asthma-like allergic airways disease in offspring. Normal pregnant mice (day 15) were subjected to a single restraint stress exposure. We subsequently tested their offspring for the development of airway hyperreactivity (AHR) and allergic airway inflammation (AI), after an intentionally suboptimal sensitization protocol. The offspring of stressed mothers showed levels of AI and enhanced airway responses to methacholine comparable to those seen in fully sensitized and challenged positive control animals; in contrast, minimal effects were seen in control offspring. Restraint stress caused a rapid and large increase in plasma corticosterone levels. Maternal treatment with dexamethasone on day 15 of pregnancy mimicked the stress effect and reproduced the AI and AHR outcomes, whereas blockade of the stress-induced corticosterone surge with metyrapone pretreatment of pregnant mice abrogated the effect. We conclude that stress-triggered glucocorticoids during pregnancy can increase susceptibility to allergy in offspring. Because inflammation typically includes a stress hormone response, the results also suggest a common pathway by which various injurious exposures during pregnancy might increase offspring susceptibility to asthma. Copyright © 2014 the American Physiological Society.

Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

NASA Technical Reports Server (NTRS)

Alberts, J. R.; Burden, H. W.; Hawes, N.; Ronca, A. E.

1996-01-01

To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

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.

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 immunization with actinomycetales immunomodulators reduces parasitemias in offspring challenged with Trypanosoma cruzi.

PubMed

Davila, Hector; Didoli, Griselda; Bottasso, Oscar; Stanford, John

2011-04-01

This article describes the first use of heat-killed, borate-buffered preparations of aerobic actinomycetales to immunize pregnant animals in order to determine the effect on their pregnancy and fertility and the survival coefficients of their offspring. Pregnant rats received three injections of Gordonia bronchialis, Rhodococcus coprophylus or physiological saline and a proportion of their offspring were challenged with live Trypanosoma cruzi at the time of weaning. Levels of parasitemia and, in some animals, of the cytokines IFN-γ and IL-10 were measured. The progress of pregnancy, fertility and survival of offspring were unaffected by the maternal immunizations. The offspring of rats immunized with G. bronchialis displayed significantly reduced parasitemias, with increased levels of IFN-γ and reduced levels of IL-10, 4 days after challenge. The offspring of rats immunized with R. coprophylus displayed greater parasitemias than did those of the control group. These unexpected results are discussed and their causation considered.

Giving offspring a head start in life: field and experimental evidence for selection on maternal basking behaviour in lizards.

PubMed

Wapstra, E; Uller, T; While, G M; Olsson, M; Shine, R

2010-03-01

The timing of birth is often correlated with offspring fitness in animals, but experimental studies that disentangle direct effects of parturition date and indirect effects mediated via variation in female traits are rare. In viviparous ectotherms, parturition date is largely driven by female thermal conditions, particularly maternal basking strategies. Our field and laboratory studies of a viviparous lizard (Niveoscincus ocellatus) show that earlier-born offspring are more likely to survive through their first winter and are larger following that winter, than are later-born conspecifics. Thus, the association between parturition date and offspring fitness is causal, rather than reflecting an underlying correlation between parturition date and maternal attributes. Survival selection on offspring confers a significant advantage for increased maternal basking in this species, mediated through fitness advantages of earlier parturition. We discuss the roles of environmentally imposed constraints and parent-offspring conflict in the evolution of maternal effects on parturition date.

Parenting behaviors associated with risk for offspring personality disorder during adulthood.

PubMed

Johnson, Jeffrey G; Cohen, Patricia; Chen, Henian; Kasen, Stephanie; Brook, Judith S

2006-05-01

Research has suggested that some types of parental child-rearing behavior may be associated with risk for offspring personality disorder (PD), but the association of parenting with offspring PD has not been investigated comprehensively with prospective longitudinal data. To investigate the association of parental child-rearing behavior with risk for offspring PD during adulthood. The Children in the Community study, a prospective longitudinal investigation. A community-based sample of 593 families interviewed during childhood (mean age, 6 years), adolescence (mean ages, 14 and 16 years), emerging adulthood (mean age, 22 years), and adulthood (mean age, 33 years) of the offspring. The Structured Clinical Interview for DSM-IV Personality Disorders. Ten types of parenting behavior that were evident during the child-rearing years were associated with elevated offspring risk for PD during adulthood when childhood behavioral or emotional problems and parental psychiatric disorders were controlled statistically. Parental behavior in the home during the child-rearing years was associated with elevated risk for offspring PD at mean ages of 22 and 33 years. Risk for offspring PD at both assessments increased steadily as a function of the number of problematic parenting behaviors that were evident. Low parental affection or nurturing was associated with elevated risk for offspring antisocial (P = .003), avoidant (P = .01), borderline (P = .002), depressive (P = .02), paranoid (P = .002), schizoid (P = .046), and schizotypal (P<.001) PDs. Aversive parental behavior (eg, harsh punishment) was associated with elevated risk for offspring borderline (P = .001), paranoid (P = .004), passive-aggressive (P = .046), and schizotypal (P = .02) PDs. Parental behavior during the child-rearing years may be associated with risk for offspring PD that endures into adulthood. This risk may not be attributable to offspring behavioral and emotional problems or parental psychiatric disorder, and it may not diminish over time. Low parental nurturing and aversive parental behavior during child rearing may both be associated with elevated risk for offspring PDs.

Near-infrared laser irradiation improves the development of mouse pre-implantation embryos

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

Yokoo, Masaki; Mori, Miho

The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing ofmore » blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. - Highlights: • Irradiation of blastocysts with a near-infrared laser improves embryo development. • Irradiation of blastocysts increases the live birth rate after embryo transfer. • Irradiation of blastocysts did not affect the normality of the pups. • Near-infrared laser irradiation may be useful to enhance the quality of embryos. • This study may contribute to improvements in reproductive technologies in mammals.« less

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

Time-limited environments affect the evolution of egg-body size allometry.

PubMed

Eckerström-Liedholm, Simon; Sowersby, Will; Gonzalez-Voyer, Alejandro; Rogell, Björn

2017-07-01

Initial offspring size is a fundamental component of absolute growth rate, where large offspring will reach a given adult body size faster than smaller offspring. Yet, our knowledge regarding the coevolution between offspring and adult size is limited. In time-constrained environments, organisms need to reproduce at a high rate and reach a reproductive size quickly. To rapidly attain a large adult body size, we hypothesize that, in seasonal habitats, large species are bound to having a large initial size, and consequently, the evolution of egg size will be tightly matched to that of body size, compared to less time-limited systems. We tested this hypothesis in killifishes, and found a significantly steeper allometric relationship between egg and body sizes in annual, compared to nonannual species. We also found higher rates of evolution of egg and body size in annual compared to nonannual species. Our results suggest that time-constrained environments impose strong selection on rapidly reaching a species-specific body size, and reproduce at a high rate, which in turn imposes constraints on the evolution of egg sizes. In combination, these distinct selection pressures result in different relationships between egg and body size among species in time-constrained versus permanent habitats. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

The Human Placenta Project: Placental Structure, Development, and Function in Real Time

PubMed Central

Guttmacher, Alan E.; Maddox, Yvonne T.; Spong, Catherine Y.

2014-01-01

Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated “Human Placenta Project,” with the ultimate goal of understanding human placental structure, development, and function in real time. PMID:24661567

The importance of calcium in improving resistance of Daphnia to Microcystis.

PubMed

Akbar, Siddiq; Du, Jingjing; Jia, Yong; Tian, Xingjun

2017-01-01

Changing environmental calcium (Ca) and rising cyanobacterial blooms in lake habitats could strongly reduce Daphnia growth and survival. Here, we assessed the effects of maternal Ca in Daphnia on transfer of resistance to their offspring against Microcystis aeruginosa PCC7806 (M. aeruginosa). Laboratory microcosm experiments were performed to examine effects in Daphnia carinata (D. carinata) and Daphnia pulex (D. pulex), and that how Ca induce responses in their offspring. The results showed that growth and survival were increased in offspring from exposed Daphnia as compared to unexposed, when raised in high Ca and increasing M. aeruginosa concentration. Among exposed Daphnia, offspring from high Ca mothers, produced more neonates with large size and higher survival as compared to offspring from low maternal Ca. Exposed D. carinata and D. pulex offspring, when reared in Ca deficient medium and increasing M. aeruginosa concentration, time to first brood increased, size become large and total offspring decreased subsequently in three alternative broods in offspring from low maternal Ca. In contrast, growth and reproduction in offspring from high Ca exposed mothers were consistent in three alternative broods. Despite species specific responses in growth, survival and variant life history traits in two Daphnia species, our results not only show maternal induction in Daphnia but also highlight that offspring response to M. aeruginosa varies with maternal Ca. This study demonstrates that Ca have role in Daphnia maternal induction against Microcystis, and recent Ca decline and increasing Microcystis concentration in lakes may decrease Daphnia growth and survival. Our data provide insights into the interactive effect of maternal Ca and Microcystis exposure on Daphnia and their outcome on offspring life history traits and survival.

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

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.

Effects of paternal age and offspring cognitive ability in early adulthood on the risk of schizophrenia and related disorders.

PubMed

Sørensen, Holger J; Pedersen, Carsten B; Nordentoft, Merete; Mortensen, Preben B; Ehrenstein, Vera; Petersen, Liselotte

2014-12-01

Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint and separate associations of paternal age and offspring IQ with the risk of SSD. We used IQ routinely measured at conscription in Danish males (n=138,966) from cohorts born in 1955-84 and in 1976-1993 and followed them from a year after the conscription through 2010. We used Cox regression to estimate the incidence rate ratio (IRR) of SSD. During the follow-up, 528 men developed SSD (incidence rate [IR] 5.2 and 8.6 per 10,000 person-years in the first and second cohorts, respectively). APA was associated with higher risk of SSD (IRR, 1.32; 95% CI, 1.10-1.60 per a ten-year increase in paternal age). A higher IQ was associated with lower SSD risk (IRR, 0.68; 95% confidence interval [CI], 0.63-0.74 per one SD increase). The IR of SSD was higher among persons who were draft-exempt for health reasons (<20% of the men). Overall, there was little evidence of lower premorbid IQ in APA-related SSD (individuals who developed SSD and were also offspring of older fathers). Our results do not support the notion that risk gradient for offspring SSD associated with paternal age is mediated by offspring IQ. Copyright © 2014 Elsevier B.V. All rights reserved.

Disturbed nitric oxide and homocysteine production are involved in the increased risk of cardiovascular diseases in the F1 offspring of maternal obesity and malnutrition.

PubMed

Moussa, Y Y; Tawfik, S H; Haiba, M M; Saad, M I; Hanafi, M Y; Abdelkhalek, T M; Oriquat, G A; Kamel, M A

2017-06-01

The present study aimed to evaluate the changes in levels of different independent risk factors for vascular diseases in the rat offspring of maternal obesity and malnutrition as maternal health disturbances are thought to have direct consequences on the offspring health. The effect of postnatal diet on the offspring was also assessed. Three groups of female Wistar rats were used (control, obese and malnourished). After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks postnatal, 20 pups (10 males and 10 females) of each subgroup were sacrificed after overnight fasting, the blood sample was obtained, and the rats were dissected out to obtain heart muscle. The following parameters were assessed; lipid profile, NEFA, homocysteine (Hcy), nitric oxide end product (NOx) and myocardial triglyceride content. Maternal obesity and malnutrition caused significant elevation in the body weight, triglycerides, NEFA, Hcy and NOx in the F1 offspring especially those maintained under HCD. Also, the male offspring showed more prominent changes than female offspring. Maternal malnutrition and obesity may increase the risk of the development of cardiovascular diseases in the offspring, especially the male ones.

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

Does route of methamphetamine exposure during pregnancy have an impact on neonatal development and behaviour in rat offspring?

PubMed

McDonnell-Dowling, Kate; Kelly, John P

2016-04-01

Many preclinical studies have aimed to elucidate the effects of methamphetamine (MA) exposure during pregnancy on the offspring in recent years. However, the severity of effects on the neonate may be related to the subcutaneous (sc) route of administration of the drug that is often employed (88% of preclinical studies) and consequently the delivered dose that the foetus is exposed to. To date there is a paucity of comparative studies investigating different routes of administration for MA during pregnancy and it is not known how these different routes compare when it comes to neonatal outcome. Thus, the aim of this study was to determine if the route of administration of MA (oral gavage or sc injection) during pregnancy at a pharmacological dose affects the magnitude of neurodevelopmental and behavioural effects in the resultant rat offspring. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (3.75 mg/kg) or control (distilled water) via oral gavage or sc injection from gestation day 7-21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. When administered sc, MA significantly reduced maternal weight gain and altered maternal behaviour; mothers spent less time in the nest with pups and spent less time nursing compared to controls. Significant impairments in neurodevelopmental parameters were evident in both MA treatment groups. Somatic development such as pinna unfolding, fur appearance and eye opening were all delayed after MA exposure but these impairments were more pronounced in the MA sc group. Other somatic parameters such as ano-genital distance and body length were only impeded by sc MA. Behavioural development in the surface righting, inclined plane and forelimb grip tests were also altered for both MA treatment groups. This study demonstrates that prenatal MA can have a profound effect on neonatal outcome, but this can be exacerbated if given via the subcutaneous route, as well as producing additional effects not seen with the oral gavage route. Consequently, the route of administration should be considered when interpreting preclinical studies investigating prenatal MA exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM:The effects of poor maternal nutrition during gestation on offspring postnatal growth and metabolism.

PubMed

Hoffman, M L; Reed, S A; Pillai, S M; Jones, A K; McFadden, K K; Zinn, S A; Govoni, K E

2017-05-01

Poor maternal nutrition during gestation has been linked to poor growth and development, metabolic dysfunction, impaired health, and reduced productivity of offspring in many species. Poor maternal nutrition can be defined as an excess or restriction of overall nutrients or specific macro- or micronutrients in the diet of the mother during gestation. Interestingly, there are several reports that both restricted- and over-feeding during gestation negatively affect offspring postnatal growth with reduced muscle and bone deposition, increased adipose accumulation, and metabolic dysregulation through reduced leptin and insulin sensitivity. Our laboratory and others have used experimental models of restricted- and over-feeding during gestation to evaluate effects on early postnatal growth of offspring. Restricted- and over-feeding during gestation alters body size, circulating growth factors, and metabolic hormones in offspring postnatally. Both restricted- and over-feeding alter muscle growth, increase lipid content in the muscle, and cause changes in expression of myogenic factors. Although the negative effects of poor maternal nutrition on offspring growth have been well characterized in recent years, the mechanisms contributing to these changes are not well established. Our laboratory has focused on elucidating these mechanisms by evaluating changes in gene and protein expression, and stem cell function. Through RNA-Seq analysis, we observed changes in expression of genes involved in protein synthesis, metabolism, cell function, and signal transduction in muscle tissue. We recently reported that satellite cells, muscle stem cells, have altered expression of myogenic factors in offspring from restricted-fed mothers. Bone marrow derived mesenchymal stem cells, multipotent cells that contribute to development and maintenance of several tissues including bone, muscle, and adipose, have a 50% reduction in cell proliferation and altered metabolism in offspring from both restricted- and over-fed mothers. These findings indicate that poor maternal nutrition may alter offspring postnatal growth by programming stem cell populations. In conclusion, poor maternal nutrition during gestation negatively affects offspring postnatal growth, potentially through impaired stem and satellite cell function. Therefore, determining the mechanisms that contribute to fetal programming is critical to identifying effective management interventions for these offspring and improving efficiency of production.

Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

PubMed

O'Brien, Jessica W; Hill, Shirley Y

2014-12-01

Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Women with a family history of SUD are at increased risk for substance use during pregnancy. Both familial loading for alcohol dependence and prenatal exposure to alcohol or cigarettes are important risk factors in the development of offspring substance use. An inadequate assessment of family history may obscure important interactions between familial risk and prenatal exposures on offspring outcomes. Copyright © 2015 by the Research Society on Alcoholism.

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents

PubMed Central

Little, Mark P.; Goodhead, Dudley T.; Bridges, Bryn A.; Bouffler, Simon D.

2013-01-01

In this article we review health effects in offspring of human populations exposed as a result of radiotherapy and some groups exposed to chemotherapy. We also assess risks in offspring of other radiation-exposed groups, in particular those of the Japanese atomic bomb survivors and occupationally and environmentally exposed groups. Experimental findings are also briefly surveyed. Animal and cellular studies tend to suggest that the irradiation of males, at least at high doses (mostly 1 Gy and above), can lead to observable effects (including both genetic and epigenetic) in the somatic cells of their offspring over several generations that are not attributable to the inheritance of a simple mutation through the parental germ line. However, studies of disease in the offspring of irradiated humans have not identified any effects on health. The available evidence therefore suggests that human health has not been significantly affected by transgenerational effects of radiation. It is possible that transgenerational effects are restricted to relatively short times post-exposure and in humans conception at short times after exposure is likely to be rare. Further research that may help resolve the apparent discrepancies between cellular/animal studies and studies of human health are outlined. PMID:23648355

[Effects of nano-lead exposure on learning and memory as well as iron homeostasis in brain of offspring rats].

PubMed

Gao, Jing; Su, Hong; Yin, Jingwen; Cao, Fuyuan; Feng, Peipei; Liu, Nan; Xue, Ling; Zheng, Guoying; Li, Qingzhao; Zhang, Yanshu

2015-06-01

To investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42). Twenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay. After nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05). n Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

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.

Adolescents of the US National Longitudinal Lesbian Family Study: the impact of having a known or an unknown donor on the stability of psychological adjustment.

PubMed

Bos, H M W; Gartrell, N K

2011-03-01

The current study is based on the US National Longitudinal Lesbian Family Study (NLLFS), which was designed to document the development of the first generation of lesbian families with children conceived through donor insemination. Data were collected in five waves, first at insemination or during pregnancy, and subsequently when the index children were 2, 5, 10 and 17 years old. The study is ongoing, with a 93% retention rate to date. The purpose of the current investigation was to assess changes in psychological adjustment of the index offspring between the time that they were 10 and 17 years old (T4 and T5) and to examine the effects of having a known or an as-yet-unknown donor. The total T5 sample consisted of 78 adolescents. The mothers in 74 families completed a Child Behaviour Checklist (CBCL) on their offspring at both T4 and T5: 26 of these offspring had been conceived through known sperm donors and 48 through unknown donors. Changes in psychological adjustment were assessed through computations of stability coefficients between T4 and T5 on all CBCL subscales, and by means of a general linear model (GLM). On 10 out of 11 CBCL subscales, the stability coefficients were not significantly different for adolescents with known and unknown donors. Findings from the GLM showed that no main effect for donor type was found; for offspring in both donor groups thought problems and rule-breaking behaviour were higher and scores on social problems and aggressive behaviour were lower at T5 than T4. The development of psychological well-being in the offspring of lesbian mothers over a 7-year period from childhood through adolescence is the same for those who were conceived through known and unknown donors.

EXPOSURE TO DEXAMETHASONE DURING LATE GESTATION CAUSES FEMALE-SPECIFIC DECREASES IN CORE BODY TEMPERATURE AND PREPRO-THYROTROPIN-RELEASING HORMONE EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS IN RATS

PubMed Central

Carbone, David L.; Zuloaga, Damian G.; Lacagnina, Anthony F.; McGivern, Robert F.; Handa, Robert J.

2012-01-01

Synthetic glucocorticoids (GC) have been used to promote lung development in preterm infants, thereby decreasing respiratory distress syndrome and mortality, yet, concern has arisen from reports that such treatment predisposes individuals to disease in adulthood. Given the variety of preclinical studies that show metabolic and behavioral abnormalities in adulthood following fetal exposure to synthetic GC, we examined the effect of in utero exposure to the synthetic GC, dexamethasone (DEX), on hypothalamic expression of thyrotropin-releasing hormone (TRH) a central neuropeptide involved in mediating behavior and metabolic balance. Pregnant Sprague-Dawley rats were administered 0.4 mg/kg DEX on gestational days 18–21. As adults (postnatal day (PD) 60), the offspring were fitted with temperature sensing transmitters allowing real-time monitoring of core body temperature (CBT) across the 24 hr light dark period. This revealed a significant decrease in CBT throughout the day in prenatal DEX-treated females on estrus and diestrus, but not in male offspring. The reduction in CBT by prenatal DEX exposure was accompanied by a significant decrease in the expression of Trh transcript in the paraventricular nucleus of the hypothalamus (PVN) of female rats at PD 60 and this effect was also present on PD7. There was also a female-specific reduction in the number of preproTRH -immunoreactive (ir) neurons in the PVN, with ppTRH-ir nerve fibers decreases that were present in both male and female offspring. No changes in thyroid hormone (triiodothyronine, T3; thyroxine, T4) were observed in adult offspring, but during development, both males and females (PD14) had lower T3 and T4 levels. These data indicate abnormal expression of TRH results from fetal DEX exposure during late gestation, possibly explaining the decreased CBT observed in the female offspring. PMID:22884559

Pubertal timing and early sexual intercourse in the offspring of teenage mothers.

PubMed

De Genna, Natacha M; Larkby, Cynthia; Cornelius, Marie D

2011-10-01

Early puberty is associated with stressful family environments, early sexual intercourse, and teenage pregnancy. We examined pubertal timing and sexual debut among the 14-year-old offspring of teenage mothers. Mothers (71% Black, 29% White) were recruited as pregnant teenagers (12-18 years old). Data were collected during pregnancy and when offspring were 6, 10 and 14 years old (n = 318). Adolescents (50% male) compared the timing of their pubertal maturation to same-sex peers. There was a significant 3-way interaction effect of race, sex, and pubertal timing on sexual debut (n = 305). This effect remained significant in a model controlling for maternal age at first intercourse, substance use, exposure to trauma, authoritative parenting, and peer sexual activity (n = 255). Early maturation was associated with early sex in daughters, and may be one pathway for the inter-generational transfer of risk for teenage pregnancy among daughters of teenage mothers.

Pubertal Timing and Early Sexual Intercourse in the Offspring of Teenage Mothers

PubMed Central

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

2011-01-01

Early puberty is associated with stressful family environments, early sexual intercourse, and teenage pregnancy. We examined pubertal timing and sexual debut among the 14-year-old offspring of teenage mothers. Mothers (71% Black, 29% White) were recruited as pregnant teenagers (12–18 years old). Data were collected during pregnancy and when offspring were 6, 10 and 14 years old (n = 318). Adolescents (50% male) compared the timing of their pubertal maturation to same-sex peers. There was a significant 3-way interaction effect of race, sex, and pubertal timing on sexual debut (n = 305). This effect remained significant in a model controlling for maternal age at first intercourse, substance use, exposure to trauma, authoritative parenting, and peer sexual activity (n = 255). Early maturation was associated with early sex in daughters, and may be one pathway for the inter-generational transfer of risk for teenage pregnancy among daughters of teenage mothers. PMID:21279428

Maternal B-vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc+/1638N mouse offspring

USDA-ARS?s Scientific Manuscript database

Variations in the intake of folate are capable of modulating colorectal tumorigenesis; however the outcome appears to be dependent on timing. We sought to determine the effect of altering folate (and related B vitamin) availability during in utero development and the suckling period on intestinal tu...

Toxic plants: Effects on reproduction and fetal and embryonic development in livestock

USDA-ARS?s Scientific Manuscript database

Reproductive performance not only relates to an animal’s ability to produce offspring, but to produce it at a proper time interval and provide proper neonatal care and nutrition. The recognition that poisonous plants may have a major impact on reproductive performance is relatively new and not full...

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

Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations

PubMed Central

Wankhade, Umesh D.; Zhong, Ying; Kang, Ping; Alfaro, Maria; Chintapalli, Sree V.; Thakali, Keshari M.

2017-01-01

Objective Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. Methods Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring. Offspring of both control diet- and HFD-fed dams were weaned onto control and HFD, creating four groups. Results When compared to their control diet-fed littermates, offspring of HF-dams weaned onto HFD gained greater body weight; had increased relative liver weight and showed hepatic steatosis and inflammation. Similarly, this group revealed significantly greater immune response and pro-fibrogenic gene expression via RNA-seq. In parallel, 7–8 week old offspring were challenged with either control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes. Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed persistent epigenetic changes in key genes in tissue development and metabolism (Fgf21, Ppargc1β) with maternal HFD and in cell adhesion and communication (VWF, Ephb2) in the combination of maternal HFD and offspring MCD diets. Maternal HFD also influenced gut microbiome profiles in offspring leading to a decrease in α-diversity. Linear regression analysis revealed association between serum ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum. Conclusion Our findings indicate that maternal HFD detrimentally alters epigenetic and gut microbiome pathways to favor development of fatty liver disease and its progressive sequelae. PMID:28414763

Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations.

PubMed

Wankhade, Umesh D; Zhong, Ying; Kang, Ping; Alfaro, Maria; Chintapalli, Sree V; Thakali, Keshari M; Shankar, Kartik

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring. Offspring of both control diet- and HFD-fed dams were weaned onto control and HFD, creating four groups. When compared to their control diet-fed littermates, offspring of HF-dams weaned onto HFD gained greater body weight; had increased relative liver weight and showed hepatic steatosis and inflammation. Similarly, this group revealed significantly greater immune response and pro-fibrogenic gene expression via RNA-seq. In parallel, 7-8 week old offspring were challenged with either control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes. Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed persistent epigenetic changes in key genes in tissue development and metabolism (Fgf21, Ppargc1β) with maternal HFD and in cell adhesion and communication (VWF, Ephb2) in the combination of maternal HFD and offspring MCD diets. Maternal HFD also influenced gut microbiome profiles in offspring leading to a decrease in α-diversity. Linear regression analysis revealed association between serum ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum. Our findings indicate that maternal HFD detrimentally alters epigenetic and gut microbiome pathways to favor development of fatty liver disease and its progressive sequelae.

Maternal obesity disrupts circadian rhythms of clock and metabolic genes in the offspring heart and liver.

PubMed

Wang, Danfeng; Chen, Siyu; Liu, Mei; Liu, Chang

2015-06-01

Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Pparα, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-α, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood.

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.

Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets.

PubMed

Fontelles, Camile Castilho; Guido, Luiza Nicolosi; Rosim, Mariana Papaléo; Andrade, Fábia de Oliveira; Jin, Lu; Inchauspe, Jessica; Pires, Vanessa Cardoso; de Castro, Inar Alves; Hilakivi-Clarke, Leena; de Assis, Sonia; Ong, Thomas Prates

2016-07-26

Although males contribute half of the embryo's genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter's breast cancer risk has been examined in few studies. Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis. Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers' sperm and their daughters' mammary glands, and to modifications in breast cancer-related protein expression in this tissue. Our findings highlight the importance of paternal nutrition in affecting future generations' risk of developing breast cancer.

Sexual Risk Behaviors in the Adolescent Offspring of Parents with Bipolar Disorder: Prospective Associations with Parents' Personality and Externalizing Behavior in Childhood.

PubMed

Nijjar, Rami; Ellenbogen, Mark A; Hodgins, Sheilagh

2016-10-01

We recently reported that adolescent and young adult offspring of parents with bipolar disorder (OBD), relative to control offspring, were more likely to engage in sexual risk behaviors (SRBs). The present prospective study aimed to determine the contribution of parents' personality and offspring behaviour problems in middle childhood to offspring SRBs 10 years later. We hypothesized that offspring externalizing problems in childhood would mediate the relationship between parents' personality traits of neuroticism and agreeableness and adolescent SRBs. Furthermore, we expected these associations to be more robust among the OBD than controls. At baseline, 102 offspring (52 OBD and 50 controls) aged between 4 and 14 years were assessed along with their parents, who completed a self-report personality measure and child behavior rating. Behaviour ratings were also obtained from the children's teachers. Ten years later the offspring completed an interview assessing SRBs. Mediation analyses using bootstrapping revealed that, after controlling for age and presence of an affective disorder, externalizing behaviors served as a pathway through which high parental neuroticism, low parental agreeableness, and low parental extraversion were related to SRBs in offspring. Moderated mediation analyses revealed that the relationship between parental neuroticism and childhood externalizing problems was stronger for OBD than controls. These findings add to our previous results showing parents' personality contributes to intergenerational risk transfer through behavioral problems in middle childhood. These results carry implications for optimal timing of preventative interventions in the OBD.

"Over time it just becomes easier…": parents of people with Angelman syndrome and Prader-Willi syndrome speak about their carer role.

PubMed

Thomson, Allyson; Glasson, Emma; Roberts, Peter; Bittles, Alan

2017-04-01

This study investigated two of the stresses experienced by parents caring for offspring with Angelman syndrome (AS) and Prader-Willi syndrome (PWS) in Western Australia, and identified their coping strategies. Parents of 19 offspring with AS and PWS participated in the Family Stress and Coping Interview which provides a stress level score, and a discussion of stressors and coping methods associated with 24 life situations, two of which are reported. All text was examined using directed content analysis. Family carers (14/19) reported high stress associated with the initial diagnosis of AS or PWS in their offspring; and finding time for themselves. Stressors identified included lack of quality information about the disorder, time constraints and physical and emotional tiredness. Parents adopted a variety of coping strategies, including learning about the disorder, accepting the situation, seeking instrumental and social supports and dealing with problems. No specific coping strategy was associated with reduced stress. However, parents felt that accurate and timely information during the diagnostic period helped. Parents used family and community support although there were difficulties accessing respite care. It is advised that government agencies, service providers, family members and peer support associations should provide practical and emotional support to assist the parents of offspring with AS and PWS, and indeed any form of intellectual disability, across the lifespan. Implications for Rehabilitation Long-term caring for offspring with AS or PWS can involve considerable stress for parents. Stress has been associated with poorer health outcomes for parental carers. Parents need a variety of practical and emotional supports to cope with stress, including timely access to information.

Does the Mother or Father Determine the Offspring Sex Ratio? Investigating the Relationship between Maternal Digit Ratio and Offspring Sex Ratio

PubMed Central

Kim, Tae Beom; Oh, Jin Kyu; Kim, Kwang Taek; Yoon, Sang Jin; Kim, Soo Woong

2015-01-01

Objective In mammals, high parental testosterone levels present around the time of conception are thought to skew offspring sex ratio toward sons. The second to fourth digit ratio (digit ratio) is now widely accepted as a negative correlate of prenatal testosterone. Thus, we investigated the association between digit ratio and offspring sex ratio. Methods A total of 508 Korean patients (257 males and 251 females) less than 60 years old who had one or more offspring were prospectively enrolled. The lengths of the 2nd and 4th digits of the right hand were measured by a single investigator using a digital vernier calliper. Next, the patients’ lifetime offspring birth sex ratios were investigated. Results Maternal (rather than paternal) digit ratio was significantly associated with the number of sons (r = -0.153, p = 0.015), number of daughters (r = 0.130, p = 0.039), and offspring sex ratio (r = -0.171, p = 0.007). And, the maternal digit ratio was a significant factor for predicting offspring sex ratio (B = -1.620, p = 0.008) on multiple linear regression analysis. The female patients with a lower digit ratio (< 0.95) were found to have a higher offspring sex ratio (0.609 versus 0.521, p = 0.046) compared to those with a higher digit ratio (≥ 0.95). Furthermore, females in the low digit ratio group have a probability 1.138 greater of having sons than females in the high digit ratio group. Conclusions Maternal digit ratio was negatively associated with offspring sex ratio. Females with a lower digit ratio were more likely to have more male offspring compared to those with a higher digit ratio. Thus, our results suggest that the sex of offspring might be more influenced by maternal rather than paternal factors. PMID:26575995

Prenatal lipopolysaccharide exposure increases anxiety-like behaviors and enhances stress-induced corticosterone responses in adult rats.

PubMed

Lin, Yu-Lung; Lin, Shu-Yi; Wang, Sabrina

2012-03-01

Maternal infection during pregnancy may affect fetal brain development and lead to neurological and mental disorders. Previously, we used lipopolysaccharide [LPS, 33 μg/kg, intraperitoneal injection] exposure on gestation day 10.5 to mimic maternal bacterial infection in rats and found reduced dopaminergic and serotoninergic neurons in the offspring. In the present study, we examined the anxiety and stress responses of the affected offspring and the neurophysiological changes in their brains. Our results show that LPS rats displayed more anxiety-like behaviors and heightened stress responses. Dopamine (DA) in the nucleus accumbens and serotonin (5-HT) in the medial prefrontal cortex and the hippocampus were significantly reduced in LPS rats. Their glucocorticoid receptors in the dorsal hippocampus and the 5-HT(1A) receptors in the dorsal and ventral hippocampus were also reduced. In addition, chronic but not acute fluoxetine treatment reversed the behavioral changes and increased hippocampal 5-HT(1A) receptor expression. This study demonstrates that LPS exposure during a critical time of embryonic development could produce long-term reduction of DA and 5-HT and other neurophysiological changes; such alterations may be associated with the increases in stress response and anxiety-like behaviors in the offspring. Copyright © 2011 Elsevier Inc. All rights reserved.

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure.

PubMed

Comasco, E; Rangmar, J; Eriksson, U J; Oreland, L

2018-01-01

Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Long-term culture of chicken primordial germ cells isolated from embryonic blood and production of germline chimaeric chickens.

PubMed

Naito, Mitsuru; Harumi, Takashi; Kuwana, Takashi

2015-02-01

Production of germline chimaeric chickens by the transfer of cultured primordial germ cells (PGC) is a useful system for germline manipulation. A novel culture system was developed for chicken PGC isolated from embryonic blood. The isolated PGC were cultured on feeder cells derived from chicken embryonic fibroblast. The cultured PGC formed colonies and they proliferated about 300-times during the first 30 days. The cultured PGC retained the ability to migrate to recipient gonads and were also chicken VASA homologue (CVH)-positive. Female PGC were present in the mixed-sex PGC populations cultured for more than 90 days and gave rise to viable offspring efficiently via germline chimaeric chickens. Male cultured PGC were transferred to recipient embryos and produced putative chimaeric chickens. The DNA derived from the cultured PGC was detected in the sperm samples of male putative chimaeric chickens, but no donor derived offspring were obtained. Donor-derived offspring were also obtained from germline chimaeric chickens by the transfer of frozen-thawed cultured PGC. The culture method for PGC developed in the present study is useful for manipulation of the germline in chickens, such as preservation of genetic resources and gene transfer. Copyright © 2014 Elsevier B.V. All rights reserved.

Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function.

PubMed

Thorsell, Annika; Nätt, Daniel

2016-08-01

It has been shown that maternal stress and malnutrition, or experience of other adverse events, during the perinatal period may alter susceptibility in the adult offspring in a time-of-exposure dependent manner. The mechanism underlying this may be epigenetic in nature. Here, we summarize some recent findings on the effects on gene-regulation following maternal malnutrition, focusing on epigenetic regulation of peptidergic activity. Numerous neuropeptides within the central nervous system are crucial components in regulation of homeostatic energy-balance, as well as affective health (i.e. health events related to affective disorders, psychiatric disorders also referred to as mood disorders). It is becoming evident that expression, and function, of these neuropeptides can be regulated via epigenetic mechanisms during fetal development, thereby contributing to the development of the adult phenotype and, possibly, modulating disease susceptibility. Here, we focus on two such neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH), both involved in regulation of endocrine function, energy homeostasis, as well as affective health. While a number of published studies indicate the involvement of epigenetic mechanisms in CRH-dependent regulation of the offspring adult phenotype, NPY has been much less studied in this context and needs further work.

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.

The effects of congenital hypothyroidism using the hyt/hyt mouse on locomotor activity and learned behavior.

PubMed

Anthony, A; Adams, P M; Stein, S A

1993-09-01

The offspring of matings between hyt/hyt male mice and hyt/+ females were examined for somatic and behavioral differences. The hyt/hyt offspring displayed delayed somatic development for eye opening and ear extension relative to their euthyroid littermates. Behavioral measurement of locomotor activity indicated hyperactivity at 14 days of age and hypoactivity at 21 and 40 days relative to the euthyroid mice. Impaired swimming escape behavior and Morris maze spatial learning were observed in the hyt/hyt animals. Comparative evaluation of +/+ progenitor strain offspring having no hypothyroidism in their genetic background indicated significant differences in somatic and behavioral endpoints between the hyt/hyt and euthyroid (hyt/+, +/+) animals. These results confirm the utility of the hyt/hyt mouse for studies of the impact of congenital hypothyroidism on the functional development of the offspring.

Maternal Antibody Transfer Can Lead to Suppression of Humoral Immunity in Developing Zebra Finches (Taeniopygia guttata)

PubMed Central

Merrill, Loren; Grindstaff, Jennifer L.

2015-01-01

Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female’s plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring’s humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipo-polysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring’s humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17–28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring. PMID:25244385

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.

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.

Increased de novo copy number variants in the offspring of older males

PubMed Central

Flatscher-Bader, T; Foldi, C J; Chong, S; Whitelaw, E; Moser, R J; Burne, T H J; Eyles, D W; McGrath, J J

2011-01-01

The offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. In light of the evidence implicating copy number variants (CNVs) with schizophrenia and autism, we used a mouse model to explore the hypothesis that the offspring of older males have an increased risk of de novo CNVs. C57BL/6J sires that were 3- and 12–16-months old were mated with 3-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, 7 distinct CNVs were identified in a set of 12 offspring and their parents. Competitive quantitative PCR confirmed these CNVs in the original set and also established their frequency in an independent set of 77 offspring and their parents. On the basis of the combined samples, six de novo CNVs were detected in the offspring of older sires, whereas none were detected in the control group. Two of the CNVs were associated with behavioral and/or neuroanatomical phenotypic features. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. This is the first experimental demonstration that the offspring of older males have an increased risk of de novo CNVs. Our results support the hypothesis that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism by generation of de novo CNVs in the male germline. PMID:22832608

Personality profile of the children of long-lived parents.

PubMed

Antoniou, Evangelia E; Dutta, Ambarish; Langa, Kenneth M; Melzer, David; Llewellyn, David

2013-09-01

Past research has shown that parental longevity is related to offspring physical health and longevity. Preliminary studies suggest that parental longevity may be linked to the offspring's personality traits. A comprehensive 5-factor personality model has been related to physical health, but the association with parental longevity has not yet been investigated. We used a 5-factor personality model to investigate the relationship between parental longevity and offspring personality. Data from the longitudinal Health and Retirement Study (HRS) was used in the analyses. Using the Midlife Development Inventory and the Life Orientation test, the relationship between parental attained age and offspring personality was assessed using regression models for both men and women. Male offspring of long-lived fathers and mothers were more likely to be open to new experiences (p < .01) and be more extroverted (p = .03) compared with male offspring of short-lived fathers or mothers. Maternal or paternal attained age had no effect on the female offspring personality traits. Personality is an important phenotype to consider when investigating genetic and environmental determinants of longevity. Further research is needed to investigate the potential of gender-specific mechanisms.

Exercise rescues obese mothers' insulin sensitivity, placental hypoxia and male offspring insulin sensitivity.

PubMed

Fernandez-Twinn, Denise S; Gascoin, Geraldine; Musial, Barbara; Carr, Sarah; Duque-Guimaraes, Daniella; Blackmore, Heather L; Alfaradhi, Maria Z; Loche, Elena; Sferruzzi-Perri, Amanda N; Fowden, Abigail L; Ozanne, Susan E

2017-03-14

The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.

Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner

PubMed Central

Jašarević, Eldin; Howard, Christopher D.; Misic, Ana M.; Beiting, Daniel P.; Bale, Tracy L.

2017-01-01

The microbiome is a regulator of host immunity, metabolism, neurodevelopment, and behavior. During early life, bacterial communities within maternal gut and vaginal compartments can have an impact on directing these processes. Maternal stress experience during pregnancy may impact offspring development by altering the temporal and spatial dynamics of the maternal microbiome during pregnancy. To examine the hypothesis that maternal stress disrupts gut and vaginal microbial dynamics during critical prenatal and postnatal windows, we used high-resolution 16S rRNA marker gene sequencing to examine outcomes in our mouse model of early prenatal stress. Consistent with predictions, maternal fecal communities shift across pregnancy, a process that is disrupted by stress. Vaginal bacterial community structure and composition exhibit lasting disruption following stress exposure. Comparison of maternal and offspring microbiota revealed that similarities in bacterial community composition was predicted by a complex interaction between maternal body niche and offspring age and sex. Importantly, early prenatal stress influenced offspring bacterial community assembly in a temporal and sex-specific manner. Taken together, our results demonstrate that early prenatal stress may influence offspring development through converging modifications to gut microbial composition during pregnancy and transmission of dysbiotic vaginal microbiome at birth. PMID:28266645

Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats

PubMed Central

Zambrano, E; Martínez-Samayoa, P M; Rodríguez-González, G L; Nathanielsz, P W

2010-01-01

Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre-pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected. PMID:20351043

[Description of Clinical and Neurocognitive Profiles in Offspring of Bipolar-Type-I Parents From a Multimodal Intervention Program: Prisma].

PubMed

Palacio-Ortíz, Juan David; Uribe-Villa, Esteban; Duque-Ríos, Paula; Gutiérrez-Briceño, Paola; Zapata-Henao, Violeta; Peña-Quintero, Cristian Esteban; López-Jaramillo, Carlos

2015-01-01

Offspring of bipolar parents are a high risk population for the develop of mental diseases, their study allow determining the genetic risk, early symptoms, prodromes and psychopathology of bipolar disorder. To describe the psychopathological characteristics and neurocognitives profiles of the offspring of bipolar type I parents. And to identify the presence of sub-syndromal symptoms in all the symptom domains. A descriptive and cross-sectional study was conducted on 110 offspring between 6 and 30 years old. Semi-structured diagnostic interviews were performed. The intelectual coeficient was determined and a neuropsychological assessment was performed on 89 offspring. The most prevalent disorder in the offspring was ADHD (27.6%), with major depression (15.5%) and separation anxiety (14.1%) also being prevalent. Seven patients of the sample were diagnosed with bipolar disorder. There was a statistically significant difference between the age groups for ADHD prevalence. The most frequent sub-syndromal symptoms were observed in the disruptive group. Alterations in the cognitive domains: attention, verbal fluency, work memory, and speed of information processing, were observed in the group younger than 18 years. The offspring of bipolar parents have an elevated rate of psychopathology and cognitive alterations. They are a high risk population for the development of mental disease. These subjects also require close longitudinal observation and early and preventive therapeuthic interventions. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Maternal immune activation alters fetal brain development through interleukin-6.

PubMed

Smith, Stephen E P; Li, Jennifer; Garbett, Krassimira; Mirnics, Karoly; Patterson, Paul H

2007-10-03

Schizophrenia and autism are thought to result from the interaction between a susceptibility genotype and environmental risk factors. The offspring of women who experience infection while pregnant have an increased risk for these disorders. Maternal immune activation (MIA) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism, making MIA a useful model of the disorders. However, the mechanism by which MIA causes long-term behavioral deficits in the offspring is unknown. Here we show that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring. A single maternal injection of IL-6 on day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent inhibition (LI) deficits in the adult offspring. Moreover, coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA prevents the PPI, LI, and exploratory and social deficits caused by poly(I:C) and normalizes the associated changes in gene expression in the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does not result in several of the behavioral changes seen in the offspring of wild-type mice after MIA. The identification of IL-6 as a key intermediary should aid in the molecular dissection of the pathways whereby MIA alters fetal brain development, which can shed new light on the pathophysiological mechanisms that predispose to schizophrenia and autism.

Sex differences in razorbill (Family: Alcidae) parent-offspring vocal recognition

NASA Astrophysics Data System (ADS)

Insley, Stephen J.; Paredes Vela, Rosana; Jones, Ian L.

2002-05-01

In this study we examines how a pattern of parental care may result in a sex bias in vocal recognition. In Razorbills (Alca torda), both sexes provide parental care to their chicks while at the nest, after which the male is the sole caregiver for an additional period at sea. Selection pressure acting on recognition behavior is expected to be strongest during the time when males and chicks are together at sea, and as a result, parent-offspring recognition was predicted to be better developed in the male parent, that is, show a paternal bias. In order to test this hypothesis, vocal playback experiments were conducted on breeding Razorbills at the Gannet Islands, Labrador, 2001. The data provide clear evidence of mutual vocal recognition between the male parent and chick but not between the female parent and chick, supporting the hypothesis that parent-offspring recognition is male biased in this species. In addition to acoustic recognition, such a bias could have important social implications for a variety of behavioral and basic life history traits such as cooperation and sex-biased dispersal.

How do demographic and social factors influence parent-offspring conflict? The case of wild black and gold howler monkeys (Alouatta caraya).

PubMed

Pavé, Romina; Kowalewski, Martín M; Zunino, Gabriel E; Giraudo, Alejandro R

2015-08-01

In this study, we examined the influence of demography and social context on mother-offspring conflict in wild black and gold howler monkeys (Alouatta caraya) inhabiting two nearby sites in northern Argentina, one comprising continuous forest and one fragmented forest. These sites differed in population density (3.25 vs. 1.04 individuals/ha), degree of home range overlap between neighboring groups (70 vs. 31%), and rate of intergroup encounters (2 vs. 0.02-1 encounters/day), though not in interbirth interval or rate of infant mortality. During a 27-month study (September 2008 through November 2010), we observed 37 mother-offspring dyads across the two sites. We found a very similar pattern of mother-offspring conflict in both populations; specifically, the sites did not differ in any of the variables used to characterize the mother-offspring relationship (the time spent in contact, the rate at which the mother makes and breaks contact, the rate at which the infant breaks contact, the rate of maternal rejection, and signs of infant distress) except one (the rate at which the infant makes contact). Although mother-offspring conflict is a dynamic process that varies over time, our results suggest that the different demographic and social contexts found at the two study sites did not have a marked effect on quantitative aspects of the mother-offspring relationship in these populations of black and gold howlers. Finally, this study suggests that the environmental variability (ecological, demographic, and social traits) leads to a set of strategies used both by infants and mothers with a main goal of conflict resolution, with mothers specifically aiming to cope with the tradeoff between current and future reproduction. © 2015 Wiley Periodicals, Inc.

Variable Variation: Annual and Seasonal Changes in Offspring Sex Ratio in a Bat

PubMed Central

Barclay, Robert M. R.

2012-01-01

Many organisms produce offspring with sex-ratios that deviate from equal numbers of males and females, and numerous adaptive explanations have been proposed. In some species, offspring sex-ratio varies across the reproductive season, again with several explanations as to why this might be adaptive. However, patterns for birds and mammals are inconsistent, and multiple factors are likely involved. Long-term studies on a variety of species may help untangle the complexity. I analyzed a long-term data set on the variation in offspring sex-ratio of the big brown bat, Eptesicus fuscus, a temperate-zone, insectivorous species. Sex ratio varied seasonally, but only in some years. Births early in the season were significantly female biased in years in which parturition occurred relatively early, but not in years with late parturition. Survival of female pups increased with earlier median birth date for the colony, and early-born females were more likely to survive and reproduce as one-year olds, compared to later-born pups. I argue that, due to the unusual timing of reproductive activities in male and female bats that hibernate, producing female offspring early in the year increases their probability of reproducing as one year olds, but this is not the case for male offspring. Thus, mothers that can give birth early in the year, benefit most by producing a female pup. The relative benefit of producing female or male offspring varies depending on the length of the growing season and thus the time available for female pups to reach sexual maturity. This suggests that not only does sex-ratio vary seasonally and among years, depending on the condition of the mother and the environment, but also likely varies geographically due to differences in season length. PMID:22570704

The role of maternal age and context-dependent maternal effects in the offspring provisioning of a long-lived marine teleost

PubMed Central

Smith, Wade D.; Spencer, Paul D.; Evans, Allison N.; Heppell, Scott A.; Heppell, Selina S.

2018-01-01

Despite evidence of maternal age effects in a number of teleost species, there have been challenges to the assertion that maternal age intrinsically influences offspring quality. From an evolutionary perspective, maternal age effects result in young females paradoxically investing in less fit offspring despite a greater potential fitness benefit that might be gained by allocating this energy to individual somatic growth. Although a narrow range of conditions could lead to a maternal fitness benefit via the production of lower quality offspring, evolutionary theorists suggest these conditions are seldom met and that the reported maternal age effects are more likely products of the environmental context. Our goal was to determine if maternal effects operated on offspring provisioning in a long-lived rockfish (genus Sebastes), and to evaluate any such effects as an intrinsic function of maternal age or a context-dependent effect of the offspring release environment. We found that offspring provisioning is a function of both maternal age and the timing of offspring release; older females exhibit increased provisioning over younger females throughout the spawning season despite a decrease in provisioning across all maternal ages as the season progresses. These findings suggest a role for both maternal age effects and a potential context-dependent maternal effect in population productivity, carrying important implications when modelling population persistence and resilience. PMID:29410808

Animal models of maternal high fat diet exposure and effects on metabolism in offspring: a meta-regression analysis.

PubMed

Ribaroff, G A; Wastnedge, E; Drake, A J; Sharpe, R M; Chambers, T J G

2017-06-01

Animal models of maternal high fat diet (HFD) demonstrate perturbed offspring metabolism although the effects differ markedly between models. We assessed studies investigating metabolic parameters in the offspring of HFD fed mothers to identify factors explaining these inter-study differences. A total of 171 papers were identified, which provided data from 6047 offspring. Data were extracted regarding body weight, adiposity, glucose homeostasis and lipidaemia. Information regarding the macronutrient content of diet, species, time point of exposure and gestational weight gain were collected and utilized in meta-regression models to explore predictive factors. Publication bias was assessed using Egger's regression test. Maternal HFD exposure did not affect offspring birthweight but increased weaning weight, final bodyweight, adiposity, triglyceridaemia, cholesterolaemia and insulinaemia in both female and male offspring. Hyperglycaemia was found in female offspring only. Meta-regression analysis identified lactational HFD exposure as a key moderator. The fat content of the diet did not correlate with any outcomes. There was evidence of significant publication bias for all outcomes except birthweight. Maternal HFD exposure was associated with perturbed metabolism in offspring but between studies was not accounted for by dietary constituents, species, strain or maternal gestational weight gain. Specific weaknesses in experimental design predispose many of the results to bias. © 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Associations of Maternal Dietary Patterns during Pregnancy with Offspring Adiposity from Birth Until 54 Months of Age

PubMed Central

Chen, Ling-Wei; Aris, Izzuddin M.; Bernard, Jonathan Y.; Tint, Mya-Thway; Chia, Airu; Colega, Marjorelee; Gluckman, Peter D.; Shek, Lynette Pei-Chi; Saw, Seang-Mei; Chong, Yap-Seng; Yap, Fabian; Godfrey, Keith M.; van Dam, Rob M.; Chong, Mary Foong-Fong; Lee, Yung Seng

2016-01-01

Most studies linking maternal diet with offspring adiposity have focused on single nutrients or foods, but a dietary pattern approach is more representative of the overall diet. We thus aimed to investigate the relations between maternal dietary patterns and offspring adiposity in a multi-ethnic Asian mother–offspring cohort in Singapore. We derived maternal dietary patterns using maternal dietary intake information at 26–28 weeks of gestation, of which associations with offspring body mass index (BMI), abdominal circumference (AC), subscapular skinfold (SS), and triceps skinfold (TS) were assessed using longitudinal data analysis (linear mixed effects (LME)) and multiple linear regression at ages 0, 3, 6, 9, 12, 15, 18, 24, 36, 48, and 54 months. Three dietary patterns were derived: (1) vegetables-fruit-and-white rice (VFR); (2) seafood-and-noodles (SfN); and (3) pasta-cheese-and-bread (PCB). In the LME model adjusting for potential confounders, each standard deviation (SD) increase in maternal VFR pattern score was associated with 0.09 mm lower offspring TS. Individual time-point analysis additionally revealed that higher VFR score was generally associated with lower postnatal offspring BMI z-score, TS, SS, and sum of skinfolds (SS + TS) at ages 18 months and older. Maternal adherence to a dietary pattern characterized by higher intakes of fruit and vegetables and lower intakes of fast food was associated with lower offspring adiposity. PMID:28025503

The impact of maternal obesity on inflammatory processes and consequences for later offspring health outcomes.

PubMed

Segovia, S A; Vickers, M H; Reynolds, C M

2017-10-01

Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.

C. elegans MRP-5 Exports Vitamin B12 from Mother to Offspring to Support Embryonic Development.

PubMed

Na, Huimin; Ponomarova, Olga; Giese, Gabrielle E; Walhout, Albertha J M

2018-03-20

Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short-chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of offspring. However, the mechanism for exporting vitamin B12 from the mother to the offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that the injection of vitamin B12 into the gonad of mrp-5 deficient mothers rescues embryonic lethality in the offspring. Altogether, our findings identify a maternal mechanism for the transit of an essential vitamin to support the development of the next generation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Maternal Malaria and Gravidity Interact to Modify Infant Susceptibility to Malaria

PubMed Central

Mutabingwa, Theonest K; Bolla, Melissa C; Li, Jin-Long; Domingo, Gonzalo J; Li, Xiaohong; Fried, Michal; Duffy, Patrick E

2005-01-01

Background In endemic areas, placental malaria due to Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive. Methods and Findings During 2002–2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery (“PM-negative”), offspring of mothers with placental malaria at delivery (“PM-positive”) were 41% more likely to experience their first parasitemia at a younger age (adjusted hazard ratio [AHR] = 1.41, 95% confidence interval [CI] 1.01–1.99). The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy (adjusted odds ratio [AOR] = 0.67, 95% CI 0.50–0.91) than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds (AOR = 0.21, 95% CI 0.09–0.47). In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia (AOR = 1.59, 95% CI 1.16–2.17). Conclusion Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring. PMID:16259531

Maternal malaria and gravidity interact to modify infant susceptibility to malaria.

PubMed

Mutabingwa, Theonest K; Bolla, Melissa C; Li, Jin-Long; Domingo, Gonzalo J; Li, Xiaohong; Fried, Michal; Duffy, Patrick E

2005-12-01

In endemic areas, placental malaria due to Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive. During 2002-2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery ("PM-negative"), offspring of mothers with placental malaria at delivery ("PM-positive") were 41% more likely to experience their first parasitemia at a younger age (adjusted hazard ratio [AHR] = 1.41, 95% confidence interval [CI] 1.01-1.99). The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy (adjusted odds ratio [AOR] = 0.67, 95% CI 0.50-0.91) than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds (AOR = 0.21, 95% CI 0.09-0.47). In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia (AOR = 1.59, 95% CI 1.16-2.17). Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring.

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.

The Placental Interleukin-6 Signaling Controls Fetal Brain Development and Behavior

PubMed Central

Wu, Wei-Li; Hsiao, Elaine Y.; Yan, Zihao; Mazmanian, Sarkis K.; Patterson, Paul H.

2016-01-01

Epidemiological studies show that maternal immune activation (MIA) during pregnancy is a risk factor for autism. However, mechanisms for how MIA affects brain development and behaviors in offspring remain poorly described. To determine whether placental interleukin-6 (IL-6) signaling is required for mediating MIA on the offspring, we generated mice with restricted deletion of the receptor for IL-6 (IL-6Rα) in placental trophoblasts (Cyp19-Cre+;Il6rafl/fl), and tested offspring of Cyp19-Cre+;Il6rafl/fl mothers for immunological, pathological and behavioral abnormalities following induction of MIA. We reveal that MIA results in acute inflammatory responses in the fetal brain. Lack of IL-6 signaling in trophoblasts effectively blocks MIA-induced inflammatory responses in the placenta and the fetal brain. Furthermore, behavioral abnormalities and cerebellar neuropathologies observed in MIA control offspring are prevented in Cyp19-Cre+;Il6rafl/fl offspring. Our results demonstrate that IL-6 activation in placenta is required for relaying inflammatory signals to the fetal brain and impacting behaviors and neuropathologies relevant to neurodevelopmental disease. PMID:27838335

Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

PubMed

Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

2014-06-01

Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

The role of python eggshell permeability dynamics in a respiration-hydration trade-off.

PubMed

Stahlschmidt, Zachary R; Heulin, Benoit; DeNardo, Dale F

2010-01-01

Parental care is taxonomically widespread because it improves developmental conditions and thus fitness of offspring. Although relatively simplistic compared with parental behaviors of other taxa, python egg-brooding behavior exemplifies parental care because it mediates a trade-off between embryonic respiration and hydration. However, because egg brooding increases gas-exchange resistance between embryonic and nest environments and because female pythons do not adjust their brooding behavior in response to the increasing metabolic requirements of developing offspring, python egg brooding imposes hypoxic costs on embryos during the late stages of incubation. We conducted a series of experiments to determine whether eggshells coadapted with brooding behavior to minimize the negative effects of developmental hypoxia. We tested the hypotheses that python eggshells (1) increase permeability over time to accommodate increasing embryonic respiration and (2) exhibit permeability plasticity in response to chronic hypoxia. Over incubation, we serially measured the atomic and structural components of Children's python (Antaresia childreni) eggshells as well as in vivo and in vitro gas exchange across eggshells. In support of our first hypothesis, A. childreni eggshells exhibited a reduced fibrous layer, became more permeable, and facilitated greater gas exchange as incubation progressed. Our second hypothesis was not supported, as incubation O(2) concentration did not affect the shells' permeabilities to O(2) and H(2)O vapor. Our results suggest that python eggshell permeability changes during incubation but that the alterations over time are fixed and independent of environmental conditions. These findings are of broad evolutionary interest because they demonstrate that, even in relatively simple parental-care models, successful parent-offspring relationships depend on adjustments made by both the parent (i.e., egg-brooding behavioral shifts) and the offspring (i.e., changes in eggshell permeability).

Molecular evidence of offspring liver dysfunction after maternal exposure to zinc oxide nanoparticles.

PubMed

Hao, Yanan; Liu, Jing; Feng, Yanni; Yu, Shuai; Zhang, Weidong; Li, Lan; Min, Lingjiang; Zhang, Hongfu; Shen, Wei; Zhao, Yong

2017-08-15

Recently, reproductive, embryonic and developmental toxicity have been considered as one important sector of nanoparticle (NP) toxicology, with some studies already suggesting varying levels of toxicity and possible transgenerational toxic effects. Even though many studies have investigated the toxic effects of zinc oxide nanoparticles (ZnO NPs), little is known of their impact on overall reproductive outcome and transgenerational effects. Previously we found ZnO NPs caused liver dysfunction in lipid synthesis. This investigation, for the first time, explored the liver dysfunction at the molecular level of gene and protein expression in offspring after maternal exposure to ZnO NPs. Three pathways were investigated: lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis at 5 different time points from embryonic day-18 to postnatal day-20. It was found that the expression of 15, 16, and 16 genes in lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis signalling pathway respectively in F1 animal liver were altered by ZnO NPs compared to ZnSO 4 . The proteins in these signalling pathways (five in each pathways analyzed) in F1 animal liver were also changed by ZnO NPs compared to ZnSO 4 . The results suggest that ZnO NPs caused maternal liver defects can also be detected in offspring that might result in problems on offspring liver development, mainly on lipid synthesis, growth, and lesions or apoptosis. Along with others, this study suggests that ZnO NPs may pose reproductive, embryonic and developmental toxicity; therefore, precautions should be taken with regard to human exposure during daily life. Copyright © 2017 Elsevier Inc. All rights reserved.

The seroprevalence of antithyroid peroxidase antibodies in bipolar families and bipolar twins: results from two longitudinal studies.

PubMed

Snijders, G; de Witte, L; Mesman, E; Kemner, S; Vonk, R; Brouwer, R; Nolen, W A; Drexhage, H A; Hillegers, M H J

2017-12-01

Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time (r s  = .72 p < .001 resp. r s  = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity.

Increased anxiety-like behavior but no cognitive impairments in adult rats exposed to constant light conditions during perinatal development.

PubMed

Roman, Erika; Karlsson, Oskar

2013-11-01

Shift-work is suggested to affect fetal development negatively. In particular, maternal hormonal disturbance arising from sleep deprivation or circadian rhythm changes may disturb fetal growth or lead to complications during pregnancy. Exposure to constant light is an environmental stressor that can affect the circadian system and has been shown to induce neurochemical and behavioral changes when used during the prenatal and/or postnatal period in experimental animals. However, studies investigating long-term effects of constant light in the offspring are sparse. An accidental power outage resulted in pregnant females being housed under constant light (LL) conditions for seven days of the offspring perinatal development (embryonic day 20 to postnatal day 4). The long-term effects of constant light on the behavior in the adult offspring were assessed by means of open field, object recognition, and water maze tests. In adulthood, LL-animals displayed an intact recognition memory and no deficits in spatial learning or memory. In the open field test, LL-animals exhibited higher anxiety-like behavior, observed as significantly more thigmotaxis and less ambulation. These results were confirmed in the other behavioral tests as the LL-animals spent less time exploring the objects in the object recognition test, and showed thigmotactic behavior also in the water maze test. The results confirm that early life experience can cause changes in brain development that shape brain function and add to the sparse literature on long-term effects of constant light conditions during perinatal development on specific behaviors in adulthood.

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.

Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization.

PubMed

van der Lubbe, Joan E M; Vreugdenhil, Jessica; Damman, Sarra; Vaneman, Joost; Klap, Jaco; Goudsmit, Jaap; Radošević, Katarina; Roozendaal, Ramon

2017-06-26

Various studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring. Using a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring. The number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed. In the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

[Effect of electromagnetic pulse irradiation on mice reproduction].

PubMed

Wang, Shui-ming; Wang, De-wen; Peng, Rui-yun; Chen, Hao-yu; Gao, Ya-bing; Cao, Xiao-zhe; Cui, Xue-mei; Zhao, Mei-lan

2003-10-01

To evaluate the effect of electromagnetic pulse (EMP) irradiation on mice reproduction. Female/male Kunming mice, 6 - 8 weeks old, prior to mating, or female after pregnancy were treated with whole body irradiation by 6 x 10(4) V/m electromagnetic pulse (EMP) for five times. The pregnant mice were killed on the 18th days, and teratological markers were analysed. EMP irradiation caused no significant changes in most of female organ weight and organ/body weight ratio. But it caused significant shortening in tail length of live foetus in the female mice before conception (prior to mating) or after pregnancy (P < 0.05), and obvious decrease in male offspring ratio (0.85 +/- 0.09 vs 1.09 +/- 0.17, P < 0.05). The male offspring ratio also significantly decreased (0.76 +/- 0.18 vs 1.09 +/- 0.17, P < 0.01) after male mice irradiated by EMP. The tail length of live foetus was shortened and male offspring sex ratio was increased after both male and female mice were irradiated by EMP. EMP irradiation also caused a significantly higher fetal death rate than normal control (P < 0.05). The embryo absorption rate was increased after irradiation except that was decreased in male mice. EMP irradiation has effect on pregnancy and offspring development in both male and female mice before mating and in female mice after pregnancy.

Prenatal Omega-3 Supplementation and Eczema Risk among Offspring at Age 36 Months.

PubMed

Berman, D; Clinton, C; Limb, R; Somers, E C; Romero, V; Mozurkewich, E

2016-01-01

Long-term follow-up was completed in 84 mother-infant pairs of 118 women who completed a randomized controlled trial of prenatal supplementation with EPA- or DHA-rich fish oil or soy oil placebo. The goal of this study was to determine whether prenatal omega-3 fatty acid supplementation protects offspring against development of early childhood allergies. Assessment of childhood allergic/atopic disease among offspring at age 36 months was performed by maternal interview using the National Health Interview Survey (NHIS) questions for childhood digestive allergies, wheezing, eczema or skin allergy, and respiratory allergy. Multiple logistic regressions examined the association between prenatal supplementation and childhood outcomes, adjusted for covariates. Eczema was reported in 26/84 (31%) of offspring at age 36 months, and was significantly more prevalent in the omega-3 supplementation groups vs. placebo: EPA 13/31 (41.9%); DHA 10/26 (38.5%); placebo 3/27 (11.1%), p=0.019. Compared to placebo, EPA and DHA were associated with ≥5 times risk of offspring eczema [odds ratios (ORs): EPA 5.8 (95% CI 1.4-23.3); DHA 5.0 (95% CI 1.2-21.0)]. After adjusting for other potential risk factors (race, birth weight, vaginal/Cesarean delivery, and maternal eczema) the magnitudes of association for omega-3 supplementation increased: EPA OR 8.1 (95% CI 1.4-45.6); DHA OR 9.6 (95% CI 1.6-58.5). Maternal eczema was also significantly associated with offspring eczema in the adjusted model: OR 10.8 (95% CI 2.1-54.3). Contrary to our hypothesis, acids supplementation compared to soy oil was associated with a substantial increase in risk of childhood eczema. This association was not observed on childhood respiratory or digestive outcomes. It is unclear if these findings were driven by unfavorable effects of omega-3s, or whether there may have been unanticipated protective effects of the soy-based placebo with regards to eczema.

Prenatal testosterone exposure worsen the reproductive performance of male rat at adulthood.

PubMed

Ramezani Tehrani, Fahimeh; Noroozzadeh, Mahsa; Zahediasl, Saleh; Ghasemi, Asghar; Piryaei, Abbas; Azizi, Fereidoun

2013-01-01

The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.

Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood

PubMed Central

Ramezani Tehrani, Fahimeh; Noroozzadeh, Mahsa; Zahediasl, Saleh; Ghasemi, Asghar; Piryaei, Abbas; Azizi, Fereidoun

2013-01-01

The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated. PMID:23967236

Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

PubMed

Nguyen, Nguyen M; de Oliveira Andrade, Fabia; Jin, Lu; Zhang, Xiyuan; Macon, Madisa; Cruz, M Idalia; Benitez, Carlos; Wehrenberg, Bryan; Yin, Chao; Wang, Xiao; Xuan, Jianhua; de Assis, Sonia; Hilakivi-Clarke, Leena

2017-07-03

Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1-F3 generations were fed only the control diet. Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p < 0.016) and F3 generation offspring of HF diet-fed dams (p < 0.040) than in the control offspring. Further, tumor latency was significantly shorter (p < 0.028) and burden higher (p < 0.027) in F1 generation HF offspring, and similar trends were seen in F3 generation HF offspring. RNA sequencing was done on normal mammary glands to identify signaling differences that may predispose to increased breast cancer risk by maternal HF intake. Analysis revealed 1587 and 4423 differentially expressed genes between HF and control offspring in F1 and F3 generations, respectively, of which 48 genes were similarly altered in both generations. Quantitative real-time polymerase chain reaction analysis validated 13 chosen up- and downregulated genes in F3 HF offspring, but only downregulated genes in F1 HF offspring. Ingenuity Pathway Analysis identified upregulation of Notch signaling as a key alteration in HF offspring. Further, knowledge-fused differential dependency network analysis identified ten node genes that in the HF offspring were uniquely connected to genes linked to increased cancer risk (ANKEF1, IGFBP6, SEMA5B), increased resistance to cancer treatments (SLC26A3), poor prognosis (ID4, JAM3, TBX2), and impaired anticancer immunity (EGR3, ZBP1). We conclude that maternal HF diet intake during pregnancy induces a transgenerational increase in offspring mammary cancer risk in mice. The mechanisms of inheritance in the F3 generation may be different from the F1 generation because significantly more changes were seen in the transcriptome.

[Cytogenetic effects in peripheral blood lymphocytes in the offspring of Chernobyl nuclear power plant accident liquidators under the influence of mitomycin C in vitro and folic acid in vivo].

PubMed

Kovaleva, V I; Bagatskaia, N V

2013-01-01

The data on cytogenetic examination concerning the offspring of the Chernobyl accident liquidators (cleanup personnel) have been obtained. It has been established that spontaneous chromosomal aberrations level before folic acid administration was 1,8 times higher than that value after its employment (4,45 to 2,42 %, p < 0,01). In lymphocyte cultures treated with mitomycin C accompanied by folic acid it was 4,5 times higher before their administration (23,95 to 5,36 %, p < 0,001). The data obtained confirm a possibility of stabilization of genetic apparatus in offspring of the Chernobyl disaster liquidators after folic acid administration.

Parents face quantity-quality trade-offs between reproduction and investment in offspring in Iceland.

PubMed

Lynch, Robert Francis

2016-05-01

How to optimally allocate time, energy and investment in an effort to maximize one's reproductive success is a fundamental problem faced by all organisms. This effort is complicated when the production of each additional offspring dilutes the total resources available for parental investment. Although a quantity-quality trade-off between producing and investing in offspring has long been assumed in evolutionary biology, testing it directly in humans is difficult, partly owing to the long generation time of our species. Using data from an Icelandic genealogy (Íslendingabók) over two centuries, I address this issue and analyse the quantity-quality trade-off in humans. I demonstrate that the primary impact of parents on the fitness of their children is the result of resources and or investment, but not genes. This effect changes significantly across time, in response to environmental conditions. Overall, increasing reproduction has negative fitness consequences on offspring, such that each additional sibling reduces an individual's average lifespan and lifetime reproductive success. This analysis provides insights into the evolutionary conflict between producing and investing in children while also shedding light on some of the causes of the demographic transition.

Quality of maternal and paternal care predicts later stress reactivity in the cooperatively-breeding marmoset (Callithrix geoffroyi).

PubMed

Birnie, Andrew K; Taylor, Jack H; Cavanaugh, Jon; French, Jeffrey A

2013-12-01

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan. Published by Elsevier Ltd.

Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood.

PubMed

Ambrosetti, Valery; Guerra, Marcelo; Ramírez, Luisa A; Reyes, Aldo; Álvarez, Daniela; Olguín, Sofía; González-Mañan, Daniel; Fernandois, Daniela; Sotomayor-Zárate, Ramón; Cruz, Gonzalo

2016-07-01

Maternal obesity during pregnancy has been related with several pathological states in offspring. However, the impact of maternal obesity on reproductive system on the progeny is beginning to be elucidated. In this work, we characterize the effect of maternal obesity on puberty onset and follicular development in adult offspring in rats. We also propose that alterations in ovarian physiology observed in offspring of obese mothers are due to increased levels of estradiol during early development. Offspring of control dams and offspring of dams exposed to a high-fat diet (HF) were studied at postnatal days (PND) 1, 7, 14, 30, 60, and 120. Body weight and onset of puberty were measured. Counting of ovarian follicles was performed at PND 60 and 120. Serum estradiol, estriol, androstenedione, FSH, LH, and insulin levels were measured by ELISA. Hepatic CYP3A2 expression was determined by Western blot. HF rats had a higher weight than controls at all ages and they also had a precocious puberty. Estradiol levels were increased while CYP3A2 expression was reduced from PND 1 until PND 60 in HF rats compared to controls. Estriol was decreased at PND60 in HF rats. Ovaries from HF rats had a decrease in antral follicles at PND60 and PND120 and an increase in follicular cysts at PND60 and PND120. In this work, we demonstrated that maternal obesity in rats alters follicular development and induces follicular cysts generation in the adult offspring. We observed that maternal obesity produces an endocrine disruption through increasing endogenous estradiol in early life. A programmed failure in hepatic metabolism of estradiol is probably the cause of its increase.

Quality of Maternal and Paternal Care Predicts Later Stress Reactivity in the Cooperatively-Breeding Marmoset (Callithrix geoffroyi)

PubMed Central

Birnie, Andrew K.; Taylor, Jack H.; Cavanaugh, Jon; French, Jeffrey A.

2013-01-01

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan. PMID:24099861

Impact of social separation during pregnancy on the manifestation of defensive behaviors related to generalized anxiety and panic throughout offspring development.

PubMed

Soliani, Flaviane Cristina de Brito Guzzo; Cabbia, Rafael; Batistela, Matheus Fitipaldi; Almeida, Amarylis Garcia; Kümpel, Vinícius Dias; Yamauchi Junior, Luiz; Andrade, Telma Gonçalves Carneiro Spera de

2017-01-01

The multiple insecurities, anatomical, physiological and psychological changes arising from the gestational period can generate an overload of stress in the mother and cause disturbances in the offspring, affecting it throughout its development. The existing analysis linking prenatal stress and offspring's anxiety have divergent results, being limited as to gestational week, type of stressor and age of progeny's assessment. Social separation has been described as a stressor that causes increase in anxiety. Thus, the present study evaluated the effects of social separation applied in one of the three gestational weeks of rat dams on the manifestation of the defensive behaviors related to generalized anxiety disorder and panic in the Elevated T Maze of the male progeny in three stages of development (1, 3 or 6 months of life). It was found, in the offspring of grouped (control) dams, increased behaviors associated with generalized anxiety disorder and a reduction of panic-like behaviors throughout development. For animals whose dams were socially separated during pregnancy, the most critical period of exposure was the 2nd gestational week, which affected the acquisition of aversive memory, demonstrated by the impairment on learning of avoidances of the offspring in all ages evaluated. Stressor exposure in this week also increased the avoidances, related to generalized anxiety of progeny in the 1st month and decreased escapes, related to panic in the 3rd month of life and, at the age of 6 months old, an inverse situation, with the reduction of the defensive behaviors associated to generalized anxiety disorder. The results show that, when assessing effects of prenatal stress on the manifestation of anxiety, not only the period of exposure is important, but also the age of offspring assessed.

Prolonged prenatal hypoxia selectively disrupts collecting duct patterning and postnatal function in male mouse offspring.

PubMed

Walton, Sarah L; Singh, Reetu R; Little, Melissa H; Bowles, Josephine; Li, Joan; Moritz, Karen M

2018-04-20

In this study we investigated whether hypoxia during late pregnancy impairs kidney development in mouse offspring, and also whether this has long-lasting consequences affecting kidney function in adulthood. Hypoxia disrupted growth of the kidney, particularly the collecting duct network, in juvenile male offspring. By mid-late adulthood, these mice developed early signs of kidney disease, notably a compromised response to water deprivation. Female offspring showed no obvious signs of impaired kidney development and did not develop kidney disease, suggesting a underlying protection mechanism from the hypoxia insult. These results help us better understand the long-lasting impact of gestational hypoxia on kidney development and the increased risk of chronic kidney disease. Prenatal hypoxia is a common perturbation to arise during pregnancy, and can lead to adverse health outcomes in later life. The long-lasting impact of prenatal hypoxia on postnatal kidney development and maturation of the renal tubules, particularly the collecting duct system, is relatively unknown. Here, we used a model of moderate chronic maternal hypoxia throughout late gestation (12% O 2 exposure from E14.5 until birth). Histological analyses revealed marked changes in the tubular architecture of male hypoxia-exposed neonates as early as postnatal day 7, with disrupted medullary development and altered expression of Ctnnb1, and Crabp2 (encoding a retinoic acid binding protein). Kidneys of RARElacZ line offspring exposed to hypoxia showed reduced β-galactosidase activity indicating reduced retinoic acid-directed transcriptional activation. Wildtype male mice exposed to hypoxia had an early decline in urine concentrating capacity, evident at 4 months of age. At 12 months of age, hypoxia-exposed male mice displayed a compromised response to a water deprivation challenge which was was correlated with altered cellular composition of the collecting duct and diminished expression of AQP2. There were no differences in the tubular structures or urine concentrating capacity between the control and hypoxia-exposed female offspring at any age. This study suggests that prenatal hypoxia selectively disrupts collecting duct patterning through altered Wnt/β-catenin and retinoic acid signaling and this results in impaired function in male mouse offspring in later life. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

PubMed

Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

2018-06-01

Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

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).

Dietary DHA during development affects depression-like behaviors and biomarkers that emerge after puberty in adolescent rats

PubMed Central

Weiser, Michael J.; Wynalda, Kelly; Salem, Norman; Butt, Christopher M.

2015-01-01

DHA is an important omega-3 PUFA that confers neurodevelopmental benefits. Sufficient omega-3 PUFA intake has been associated with improved mood-associated measures in adult humans and rodents, but it is unknown whether DHA specifically influences these benefits. Furthermore, the extent to which development and puberty interact with the maternal diet and the offspring diet to affect mood-related behaviors in adolescence is poorly understood. We sought to address these questions by 1) feeding pregnant rats with diets sufficient or deficient in DHA during gestation and lactation; 2) weaning their male offspring to diets that were sufficient or deficient in DHA; and 3) assessing depression-related behaviors (forced swim test), plasma biomarkers [brain-derived neurotrophic factor (BDNF), serotonin, and melatonin], and brain biomarkers (BDNF) in the offspring before and after puberty. No dietary effects were detected when the offspring were evaluated before puberty. In contrast, after puberty depressive-like behavior and its associated biomarkers were worse in DHA-deficient offspring compared with animals with sufficient levels of DHA. The findings reported here suggest that maintaining sufficient DHA levels throughout development (both pre- and postweaning) may increase resiliency to emotional stressors and decrease susceptibility to mood disorders that commonly arise during adolescence. PMID:25411442

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.

Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age.

PubMed

Bhate, V K; Joshi, S M; Ladkat, R S; Deshmukh, U S; Lubree, H G; Katre, P A; Bhat, D S; Rush, E C; Yajnik, C S

2012-04-01

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity.

PubMed

Le Blanc, Solange; Villarroel, Pia; Candia, Valeria; Gavilán, Natalia; Soto, Néstor; Pérez-Bravo, Francisco; Arredondo, Miguel

2012-08-01

Type 2 diabetes (T2D) is directly related to alterations in iron status, oxidative stress and decreased mitochondrial activity, but the possible interaction of these parameters among T2D patients and their offspring is unclear. The whole study included 301 subjects: 77 T2D patients and one of their offspring and 51 control subjects with one of their offspring. The offspring were older than 20 years old. We measured parameters of iron status (serum iron, ferritin and transferrin receptor), diabetes (pre and post-prandial glucose, insulin, lipids), oxidative stress (Heme oxygenase activity, TBARS, SOD, GSH, Vitamin E), as well as the expression of genes in blood leukocytes related to mitochondrial apopotosis (mitofusin and Bcl/Bax ratios). The offspring of T2D patients had increased levels of serum ferritin (P < 0.01) and lower transferrin receptor (P < 0.008); higher insulin (P < 0.03) and total and LDL cholesterol; higher heme oxygenase and SOD activities increased TBARS and lower GSH; decreased mitofusin and Bcl/Bax expression ratios compared to offspring of normal subjects. These results suggest that the offspring of T2D patients could have an increased metabolic risk of develop a cardiovascular disease mediated by oxidative stress and iron status.

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

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.

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

Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

PubMed Central

Li, M.; Sloboda, D. M.; Vickers, M. H.

2011-01-01

The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring. PMID:21969822

Cognitive-emotional hyperarousal in the offspring of parents vulnerable to insomnia: a nuclear family study.

PubMed

Fernandez-Mendoza, Julio; Shaffer, Michele L; Olavarrieta-Bernardino, Sara; Vgontzas, Alexandros N; Calhoun, Susan L; Bixler, Edward O; Vela-Bueno, Antonio

2014-10-01

Cognitive-emotional hyperarousal is believed to be a predisposing factor for insomnia; however, there is limited information on the association of familial vulnerability to insomnia and cognitive-emotional hyperarousal. The aim of this study was to estimate the heritability of stress-related insomnia and examine whether parental vulnerability to stress-related insomnia is associated with cognitive-emotional hyperarousal in their offspring. We studied a volunteer sample of 135 nuclear families comprised of 270 middle-aged (51.5 ± 5.4 years) fathers and mothers and one of their biological offspring (n = 135, 20.2 ± 1.1 years). We measured vulnerability to stress-related insomnia (i.e. Ford Insomnia Response to Stress Test: FIRST), perceived stress, depression and anxiety in all participants, and arousability, presleep cognitive and somatic arousal, coping and personality in the offspring. We found a heritability estimate of 29% for FIRST scores. High FIRST parents had three to seven times the odds of having offspring highly vulnerable to stress-related insomnia. Offspring of high FIRST parents showed higher arousability, presleep cognitive arousal and emotion-oriented coping. Furthermore, high FIRST mothers contributed to offspring's higher anxiety and lower task-oriented coping, while high FIRST fathers contributed to offspring's higher presleep somatic arousal and conscientiousness. Vulnerability to stress-related insomnia is significantly heritable. Parents vulnerable to stress-related insomnia have offspring with cognitive-emotional hyperarousal who rely upon emotion-oriented coping. These data give support to the notion that arousability and maladaptive coping are key factors in the aetiology of insomnia. © 2014 European Sleep Research Society.

Paternal Body Mass Index (BMI) Is Associated with Offspring Intrauterine Growth in a Gender Dependent Manner

PubMed Central

Chen, You-Peng; Xiao, Xiao-Min; Li, Jian; Reichetzeder, Christoph; Wang, Zi-Neng; Hocher, Berthold

2012-01-01

Background Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. Conclusions Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion. PMID:22570703

Maternal corticosterone exposure has transgenerational effects on grand-offspring.

PubMed

Khan, Nicola; Peters, Richard A; Richardson, Emily; Robert, Kylie A

2016-11-01

The hormone fluctuations that an animal experiences during ovulation can have lifelong effects on developing offspring. These hormones may act as an adaptive mechanism, allowing offspring to be 'pre-programmed' to survive in an unstable environment. Here, we used a transgenerational approach to examine the effects of elevated maternal corticosterone (CORT) on the future reproductive success of female offspring. We show that female zebra finches (Taeniopygia guttata) exposed to embryonic CORT produce daughters that have equal reproductive success (clutch sizes, fertility, hatching success) compared with the daughters produced from untreated mothers, but their offspring had accelerated post-hatching growth rates and were significantly heavier by nutritional independence. Although there was no significant effect on primary offspring sex ratio, females from CORT-treated mothers produced significantly female-biased clutches by nutritional independence. To the best of our knowledge, this is the first record of a transgenerational sex ratio bias in response to elevated maternal CORT in any avian species. © 2016 The Author(s).

Motorboat noise impacts parental behaviour and offspring survival in a reef fish.

PubMed

Nedelec, Sophie L; Radford, Andrew N; Pearl, Leanne; Nedelec, Brendan; McCormick, Mark I; Meekan, Mark G; Simpson, Stephen D

2017-06-14

Anthropogenic noise is a pollutant of international concern, with mounting evidence of disturbance and impacts on animal behaviour and physiology. However, empirical studies measuring survival consequences are rare. We use a field experiment to investigate how repeated motorboat-noise playback affects parental behaviour and offspring survival in the spiny chromis ( Acanthochromis polyacanthus ), a brooding coral reef fish. Repeated observations were made for 12 days at 38 natural nests with broods of young. Exposure to motorboat-noise playback compared to ambient-sound playback increased defensive acts, and reduced both feeding and offspring interactions by brood-guarding males. Anthropogenic noise did not affect the growth of developing offspring, but reduced the likelihood of offspring survival; while offspring survived at all 19 nests exposed to ambient-sound playback, six of the 19 nests exposed to motorboat-noise playback suffered complete brood mortality. Our study, providing field-based experimental evidence of the consequences of anthropogenic noise, suggests potential fitness consequences of this global pollutant. © 2017 The Authors.

Fish oil improves lipid profile in juvenile rats with intrauterine growth retardation by altering the transcriptional expression of lipid-related hepatic genes.

PubMed

Chen, Lian-Hui; Liang, Li; Fang, Yan-Lan; Wang, Ying-Min; Zhu, Wei-Fen

2016-10-01

To determine whether maternal intrauterine undernutrition and post-weaning fish oil intake influence lipid profile in juvenile offspring, and explore the possible mechanisms at transcriptional levels. After weaning, 32 control offspring and 24 intrauterine growth retardation (IUGR) offspring were randomly allocated to standard chow or fish oil diet. At 10 weeks, fasting plasma glucose, triglycerides, total cholesterol and expressions of related hepatic genes were examined. IUGR offspring without catch-up growth tended to develop hyperglycemia, dyslipidemia and hepatic steatosis. Down-regulation of CPT-1 and LDLR at transcriptional levels were found in IUGR offspring. Early short-term fish oil intervention reversed these unfavorable changes in juvenile rats with IUGR. The mechanisms might be mediated by decreased expression of ACC-1, increased expression of CPT-1, LDLR and ABCG5. These data suggest that IUGR offspring already present lipid abnormality in juvenile stage, and early short-term fish oil consumption is beneficial to prevent these unfavorable changes.

Maternal education and risk of offspring death; changing patterns from 16 weeks of gestation until one year after birth.

PubMed

Carlsen, Fredrik; Grytten, Jostein; Eskild, Anne

2014-02-01

The social disparity in perinatal mortality may vary by the age of the offspring. We studied offspring mortality from pregnancy week 16 until 1 year after birth by maternal educational level. We included all births in Norwegian women during the years 1999-2004 (n = 297 663). The Medical Birth Registry of Norway was linked to the Norwegian Education Registry to obtain individual information on maternal education at the time of delivery. Information on infant mortality was obtained by linkage to the Norwegian Central Person Registry. In pregnancy weeks 37 through 43 and in the first week after birth, there was little difference in offspring mortality by maternal education. Before pregnancy week 37, the excess offspring mortality associated with compulsory school only was >60% using university/college education as the reference. During the 2nd through 12th month after birth, the excess mortality was 132% in offspring of mothers with compulsory school only. The social disparity in offspring mortality was lowest in pregnancies at term and in the first week after birth. In this period, all women living in Norway and their infants use the public health care service extensively. Our results may suggest that health care that is equally available to all citizens, reduces social disparities in mortality.

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.

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.

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 traumatization in the offspring. The studies also provide initial evidence that these processes can transpire even when offspring do not have probable PTSD or when controlling offspring anxiety symptoms. Our findings allude to additional behavioral and epigenetic processes that are potentially involved in the effect of parental PTSD on offspring aging, and further imply the need to develop interdisciplinary interventions aiming at promoting successful aging among offspring of traumatized parents. PMID:28706503

Geographical differences in maternal basking behaviour and offspring growth rate in a climatically widespread viviparous reptile.

PubMed

Cadby, Chloé D; Jones, Susan M; Wapstra, Erik

2014-04-01

In reptiles, the thermal environment during embryonic development affects offspring phenotypic traits and potentially offspring fitness. In viviparous species, mothers can potentially manipulate the embryonic thermal environment through their basking behaviour and, thus, may be able to manipulate offspring phenotype and increase offspring fitness. One way in which mothers can maximise offspring phenotype (and thus potentially affect offspring fitness) is by fine-tuning their basking behaviour to the environment in order to buffer the embryo from deleterious developmental temperatures. In widespread species, it is unclear whether populations that have evolved under different climatic conditions will exhibit different maternal behaviours and/or thermal effects on offspring phenotype. To test this, we provided extended or reduced basking opportunity to gravid spotted skinks (Niveoscincus ocellatus) and their offspring from two populations at the climatic extremes of the species' distribution. Gravid females fine-tuned their basking behaviour to the basking opportunity, which allowed them to buffer their embryos from potentially negative thermal effects. This fine-tuning of female basking behaviour appears to have led to the expression of geographical differences in basking behaviour, with females from the cold alpine regions being more opportunistic in their basking behaviour than females from the warmer regions. However, those differences in maternal behaviour did not preclude the evolution of geographic differences in thermal effects: offspring growth varied between populations, potentially suggesting local adaptation to basking conditions. Our results demonstrate that maternal effects and phenotypic plasticity can play a significant role in allowing species to cope in changing environmental conditions, which is particularly relevant in the context of climate change.

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

Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: II. Prenatal and Postnatal Developmental Toxicity and Maternal Function Study.

PubMed

Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

2016-09-01

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes. © The Author(s) 2016.

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

PubMed Central

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

2017-01-01

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

The Need for Future Alternatives: An Investigation of the Experiences and Future of Older Parents Caring for Offspring with Learning Disabilities over a Prolonged Period of Time

ERIC Educational Resources Information Center

Cairns, Deborah; Tolson, Debbie; Brown, Jayne; Darbyshire, Chris

2013-01-01

This article reports on the results of a qualitative study (in-depth interviews) carried out in the United Kingdom as part of a larger (two-phased) study investigating the experiences, health and future perspectives of older parent carers (six mothers and two fathers) of offspring with learning disabilities over a prolonged period of time. The…

Predicted 25-hydroxyvitamin D Score and incident type 2 diabetes in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). Our objective was to examine the relation between vitamin D status and incidence of T2D. We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict...

Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). Our objective was to examine the relation between vitamin D status and incidence of T2D. We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict...

Offspring sex in a TSD gecko correlates with an interaction between incubation temperature and yolk steroid hormones

NASA Astrophysics Data System (ADS)

Ding, Guo-Hua; Yang, Jing; Wang, Jin; Ji, Xiang

2012-12-01

We incubated eggs of the Japanese gecko Gekko japonicus at three temperatures, and measured yolk testosterone (T) and 17β-estradiol (E2) levels at three time points in embryonic development (oviposition, 1/3 of incubation, and 2/3 of incubation), to examine whether maternal influence on offspring sex via yolk steroid hormone deposition is significant in the species. Eggs incubated at 24 °C and 32 °C produced mostly females, and eggs incubated at 28 °C almost a 50:50 sex ratio of hatchlings. Female-producing eggs were larger than male-producing eggs. Clutches in which eggs were incubated at the same temperature produced mostly same-sex siblings. Yolk T level at laying was negatively related to eggs mass, and yolk E2/T ratio was positively related to egg mass. Results of two-way ANOVA with incubation temperature and stage as the factors show that: yolk E2 level was higher at 32 °C than at 24 °C; yolk T level was higher, whereas yolk E2/T ratio was smaller, at 28 °C than at 24 °C; yolk E2 and T levels were higher at 2/3 than at 1/3 of incubation. Our data in G. japonucus show that: (1) maternal influence on offspring sex via yolk steroid hormone deposition is significant; (2) incubation temperature affects the dynamics of developmental changes in yolk steroid hormones; (3) influences of yolk steroid hormones on offspring sex are secondary relative to incubation temperature effects; and (4) offspring sex correlates with an interaction between incubation temperature and yolk steroid hormones.

Offspring sex in a TSD gecko correlates with an interaction between incubation temperature and yolk steroid hormones.

PubMed

Ding, Guo-Hua; Yang, Jing; Wang, Jin; Ji, Xiang

2012-12-01

We incubated eggs of the Japanese gecko Gekko japonicus at three temperatures, and measured yolk testosterone (T) and 17β-estradiol (E2) levels at three time points in embryonic development (oviposition, 1/3 of incubation, and 2/3 of incubation), to examine whether maternal influence on offspring sex via yolk steroid hormone deposition is significant in the species. Eggs incubated at 24 °C and 32 °C produced mostly females, and eggs incubated at 28 °C almost a 50:50 sex ratio of hatchlings. Female-producing eggs were larger than male-producing eggs. Clutches in which eggs were incubated at the same temperature produced mostly same-sex siblings. Yolk T level at laying was negatively related to eggs mass, and yolk E2/T ratio was positively related to egg mass. Results of two-way ANOVA with incubation temperature and stage as the factors show that: yolk E2 level was higher at 32 °C than at 24 °C; yolk T level was higher, whereas yolk E2/T ratio was smaller, at 28 °C than at 24 °C; yolk E2 and T levels were higher at 2/3 than at 1/3 of incubation. Our data in G. japonucus show that: (1) maternal influence on offspring sex via yolk steroid hormone deposition is significant; (2) incubation temperature affects the dynamics of developmental changes in yolk steroid hormones; (3) influences of yolk steroid hormones on offspring sex are secondary relative to incubation temperature effects; and (4) offspring sex correlates with an interaction between incubation temperature and yolk steroid hormones.

Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects.

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

Kodavanti, Prasada; Coburn, Cary; Moser, Virginia

2010-06-01

Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.7, 10.2, or 30.6 mg/kg/day DE-71 in corn oil by oral gavage from gestational day 6 to weaning. DE-71 did not alter maternal or male offspring body weights. However, female offspring were smaller compared with controls from postnatal days (PNDs) 35-60. Although several neurobehavioral endpoints were assessed, the only statistically significant behavioral findingmore » was a dose-by-age interaction in the number of rears in an open-field test. Developmental exposure to DE-71 caused severe hypothyroxinemia in the dams and early postnatal offspring. DE-71 also affected anogenital distance and preputial separation in male pups. Body weight gain over time, reproductive tissue weights, and serum testosterone concentrations at PND 60 were not altered. Mammary gland development of female offspring was significantly affected at PND 21. Congener-specific analysis of PBDEs indicated accumulation in all tissues examined. Highest PBDE concentrations were found in fat including milk, whereas blood had the lowest concentrations on a wet weight basis. PBDE concentrations were comparable among various brain regions. Thus, perinatal exposure to DE-71 leads to accumulation of PBDE congeners in various tissues crossing blood-placenta and blood-brain barriers, causing subtle changes in some parameters of neurobehavior and dramatic changes in circulating thyroid hormone levels, as well as changes in both male and female reproductive endpoints. Some of these effects are similar to those seen with PCBs, and the persistence of these changes requires further investigation.« less

Prenatal Docosahexaenoic Acid Supplementation Does Not Affect Nonfasting Serum Lipid and Glucose Concentrations of Offspring at 4 Years of Age in a Follow-Up of a Randomized Controlled Clinical Trial in Mexico.

PubMed

Gutierrez-Gomez, Yareni; Stein, Aryeh D; Ramakrishnan, Usha; Barraza-Villarreal, Albino; Moreno-Macias, Hortensia; Aguilar-Salinas, Carlos; Romieu, Isabelle; Rivera, Juan A

2017-02-01

Docosahexaenoic acid (DHA) has regulatory effects on lipid and glucose metabolism. Differences in DHA availability during specific developmental windows may program metabolic changes. We investigated the effects of maternal DHA supplementation during pregnancy on the nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. We used data from the Prenatal Omega-3 Fatty Acid Supplementation, Growth, and Development trial, a double-blind randomized controlled trial conducted in Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from 18-22 wk of gestation to delivery. The primary outcomes of the trial were offspring growth and neurological development. Nonfasting blood samples were obtained from the offspring at 4 y of age. We analyzed serum total, HDL, non-HDL, and LDL cholesterol; the total-to-HDL cholesterol ratio; apolipoprotein B (apoB); triglycerides; glucose; and insulin as secondary outcomes and compared their concentrations between treatment groups. Data from 524 offspring were available. The women were compliant with the intervention based on pill counts and changes in cord blood and breast milk DHA concentrations. None of the between-group differences (DHA compared with placebo), adjusted for maternal height and time since last food intake, were significant (P range 0.27-0.83). Means (95% CIs) were as follows: total cholesterol (TC), 1.73 mg/dL (-2.63, 6.09 mg/dL); HDL cholesterol, 0.66 mg/dL (-1.07, 2.39 mg/dL); non-HDL cholesterol, 1.77 mg/dL (-1.83, 5.37 mg/dL); LDL cholesterol, 1.62 mg/dL (-2.21, 5.45 mg/dL); TC:HDL ratio, 0.01 (-0.09, 0.11); apoB, -0.15 mg/dL (-2.78, 2.48 mg/dL); triglycerides, 0.21 mg/dL (-10.93, 10.52 mg/dL); glucose, -0.67 mg/dL (-2.46, 1.11 mg/dL); and insulin, 0.62 μU/mL (-0.88, 2.11 μU/mL). Prenatal DHA supplementation does not affect nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. This trial was registered at clinicaltrials.gov as NCT00646360. © 2017 American Society for Nutrition.

Maternal Obesity and Excessive Gestational Weight Gain Are Associated with Components of Child Cognition.

PubMed

Pugh, Sarah J; Richardson, Gale A; Hutcheon, Jennifer A; Himes, Katherine P; Brooks, Maria M; Day, Nancy L; Bodnar, Lisa M

2015-11-01

Maternal overweight and obesity affect two-thirds of women of childbearing age and may increase the risk of impaired child cognition. Our objective was to test the hypothesis that high/low gestational weight gain (GWG) and high/low prepregnancy BMI were associated with offspring intelligence quotient (IQ) and executive function at age 10. Mother-infant dyads (n = 763) enrolled in a birth cohort study were followed from early pregnancy to 10 y postpartum. IQ was assessed by trained examiners with the use of the Stanford Binet Intelligence Scale-4th edition. Executive function was assessed by the number of perseverative errors on the Wisconsin Card Sorting Test and time to complete Part B on the Trail Making Test. Self-reported total GWG was converted to gestational-age-standardized GWG z score. Multivariable linear regression and negative binomial regression were used to estimate independent and joint effects of GWG and BMI on outcomes while adjusting for covariates. At enrollment, the majority of women in the Maternal Health Practices and Child Development cohort were unmarried and unemployed, and more than one-half reported their race as black. The mean ± SD GWG z score was -0.5 ± 1.8, and 27% of women had a pregravid BMI ≥ 25. The median (IQR) number of perseverative errors was 23 (17, 29), the mean ± SD time on Part B was 103 ± 42.6 s, and 44% of children had a low average IQ (≤ 89). Maternal obesity was associated with 3.2 lower IQ points (95% CI: -5.6, -0.8) and a slower time to complete the executive function scale Part B (adjusted β: 12.7 s; 95% CI: 2.8, 23 s) compared with offspring of normal-weight mothers. Offspring of mothers whose GWG was >+1 SD, compared with -1 to +1 SD, performed 15 s slower on the executive function task (95% CI: 1.8, 28 s). There was no association between GWG z score and offspring composite IQ score (adjusted β: -0.32; 95% CI: -0.72, 0.10). Prepregnancy BMI did not modify these associations. Although GWG may be important for executive function, maternal BMI has a stronger relation than GWG to both offspring intelligence and executive function. Our findings contribute to evidence linking maternal obesity to long-term child outcomes. © 2015 American Society for Nutrition.

Implications of temporal variation in maternal care for the prediction of neurobiological and behavioral outcomes in offspring

PubMed Central

Peña, Catherine Jensen; Champagne, Frances A.

2014-01-01

Previous studies in Long-Evans rats demonstrated a significant relationship between variation in pup licking/grooming and arched-back nursing (LG-ABN) and offspring development. However, maternal care is dynamic and exhibits significant temporal variation. In the current study, we assessed temporal variation in LG and ABN in lactating rats across the circadian cycle and determined the impact of these behaviors for the prediction of offspring hypothalamic gene expression, anxiety-like behavior, and responsiveness to high fat diet (HFD). We find that distinguishing between dams that engage in stable individual differences in maternal behavior (Low, Mid, High) requires assessment across the light-dark phases of the light cycle and across multiple postpartum days. Amongst juvenile female offspring, we find a positive correlation between maternal LG and mRNA levels of estrogen receptor alpha and beta and the oxytocin receptor (when LG is assessed across the light-dark cycle or in the dark phase). In young adults, we find sex-specific effects, with female High LG offspring exhibiting increased exploration of a novel environment and increased latency to approach HFD and male High LG offspring displaying increased activity in a novel environment and reduced HFD consumption. Importantly, these effects on behavior were primarily evident when LG was assessed across the light-dark cycle and ABN was not associated with these measures. Overall, our findings illustrate the dissociation between the effects of LG and ABN on offspring development and provide critical insights into the temporal characteristics of maternal behavior that have methodological implications for the study of maternal effects. PMID:23398440

Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning

PubMed Central

Borengasser, Sarah J.; Lau, Franchesca; Kang, Ping; Blackburn, Michael L.; Ronis, Martin J. J.; Badger, Thomas M.; Shankar, Kartik

2011-01-01

In utero exposure to maternal obesity increases the offspring's risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND)21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams at PND21. Indirect calorimetry revealed decreases in energy expenditure (p<0.001) and increases in RER values (p<0.001), which were further exacerbated by high fat diet (45% kcals from fat) consumption indicating an impaired ability to utilize fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial function is known to be associated with fatty acid oxidation (FAO) in the liver. Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p = 0.012) and mitochondrial protein content (p = 0.002), electron transport chain complexes (II, III, and ATPase), and fasting PGC-1α mRNA expression (p<0.001). Moreover, hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p<0.001) but was also hyperacetylated in offspring of obese dams (p<0.005) suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduces hepatic fatty acid oxidation and precedes the development of detrimental obesity associated co-morbidities such as insulin resistance and NAFLD. PMID:21901160

Nature vs. nurture: Evidence for social learning of conflict behaviour in grizzly bears

USGS Publications Warehouse

Morehouse, Andrea T.; Graves, Tabitha A.; Mikle, Nathaniel; Boyce, Mark S.

2016-01-01

The propensity for a grizzly bear to develop conflict behaviours might be a result of social learning between mothers and cubs, genetic inheritance, or both learning and inheritance. Using non-invasive genetic sampling, we collected grizzly bear hair samples during 2011–2014 across southwestern Alberta, Canada. We targeted private agricultural lands for hair samples at grizzly bear incident sites, defining an incident as an occurrence in which the grizzly bear caused property damage, obtained anthropogenic food, or killed or attempted to kill livestock or pets. We genotyped 213 unique grizzly bears (118 M, 95 F) at 24 microsatellite loci, plus the amelogenin marker for sex. We used the program COLONY to assign parentage. We evaluated 76 mother-offspring relationships and 119 father-offspring relationships. We compared the frequency of problem and non-problem offspring from problem and non-problem parents, excluding dependent offspring from our analysis. Our results support the social learning hypothesis, but not the genetic inheritance hypothesis. Offspring of problem mothers are more likely to be involved in conflict behaviours, while offspring from non-problem mothers are not likely to be involved in incidents or human-bear conflicts themselves (Barnard’s test, p = 0.05, 62.5% of offspring from problem mothers were problem bears). There was no evidence that offspring are more likely to be involved in conflict behaviour if their fathers had been problem bears (Barnard’s test, p = 0.92, 29.6% of offspring from problem fathers were problem bears). For the mother-offspring relationships evaluated, 30.3% of offspring were identified as problem bears independent of their mother’s conflict status. Similarly, 28.6% of offspring were identified as problem bears independent of their father’s conflict status. Proactive mitigation to prevent female bears from becoming problem individuals likely will help prevent the perpetuation of conflicts through social learning.

Nature vs. Nurture: Evidence for Social Learning of Conflict Behaviour in Grizzly Bears.

PubMed

Morehouse, Andrea T; Graves, Tabitha A; Mikle, Nate; Boyce, Mark S

2016-01-01

The propensity for a grizzly bear to develop conflict behaviours might be a result of social learning between mothers and cubs, genetic inheritance, or both learning and inheritance. Using non-invasive genetic sampling, we collected grizzly bear hair samples during 2011-2014 across southwestern Alberta, Canada. We targeted private agricultural lands for hair samples at grizzly bear incident sites, defining an incident as an occurrence in which the grizzly bear caused property damage, obtained anthropogenic food, or killed or attempted to kill livestock or pets. We genotyped 213 unique grizzly bears (118 M, 95 F) at 24 microsatellite loci, plus the amelogenin marker for sex. We used the program COLONY to assign parentage. We evaluated 76 mother-offspring relationships and 119 father-offspring relationships. We compared the frequency of problem and non-problem offspring from problem and non-problem parents, excluding dependent offspring from our analysis. Our results support the social learning hypothesis, but not the genetic inheritance hypothesis. Offspring of problem mothers are more likely to be involved in conflict behaviours, while offspring from non-problem mothers are not likely to be involved in incidents or human-bear conflicts themselves (Barnard's test, p = 0.05, 62.5% of offspring from problem mothers were problem bears). There was no evidence that offspring are more likely to be involved in conflict behaviour if their fathers had been problem bears (Barnard's test, p = 0.92, 29.6% of offspring from problem fathers were problem bears). For the mother-offspring relationships evaluated, 30.3% of offspring were identified as problem bears independent of their mother's conflict status. Similarly, 28.6% of offspring were identified as problem bears independent of their father's conflict status. Proactive mitigation to prevent female bears from becoming problem individuals likely will help prevent the perpetuation of conflicts through social learning.

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 effect of maternal HF diet. PMID:21464991

Nature vs. Nurture: Evidence for Social Learning of Conflict Behaviour in Grizzly Bears

PubMed Central

Morehouse, Andrea T.; Graves, Tabitha A.; Mikle, Nate; Boyce, Mark S.

2016-01-01

The propensity for a grizzly bear to develop conflict behaviours might be a result of social learning between mothers and cubs, genetic inheritance, or both learning and inheritance. Using non-invasive genetic sampling, we collected grizzly bear hair samples during 2011–2014 across southwestern Alberta, Canada. We targeted private agricultural lands for hair samples at grizzly bear incident sites, defining an incident as an occurrence in which the grizzly bear caused property damage, obtained anthropogenic food, or killed or attempted to kill livestock or pets. We genotyped 213 unique grizzly bears (118 M, 95 F) at 24 microsatellite loci, plus the amelogenin marker for sex. We used the program COLONY to assign parentage. We evaluated 76 mother-offspring relationships and 119 father-offspring relationships. We compared the frequency of problem and non-problem offspring from problem and non-problem parents, excluding dependent offspring from our analysis. Our results support the social learning hypothesis, but not the genetic inheritance hypothesis. Offspring of problem mothers are more likely to be involved in conflict behaviours, while offspring from non-problem mothers are not likely to be involved in incidents or human-bear conflicts themselves (Barnard’s test, p = 0.05, 62.5% of offspring from problem mothers were problem bears). There was no evidence that offspring are more likely to be involved in conflict behaviour if their fathers had been problem bears (Barnard’s test, p = 0.92, 29.6% of offspring from problem fathers were problem bears). For the mother-offspring relationships evaluated, 30.3% of offspring were identified as problem bears independent of their mother’s conflict status. Similarly, 28.6% of offspring were identified as problem bears independent of their father’s conflict status. Proactive mitigation to prevent female bears from becoming problem individuals likely will help prevent the perpetuation of conflicts through social learning. PMID:27851753

Hair Mercury Concentrations in Western Hudson Bay Polar Bear Family Groups.

PubMed

Bechshoft, Thea; Derocher, Andrew E; Richardson, Evan; Lunn, Nicholas J; St Louis, Vincent L

2016-05-17

Methylmercury is one of the more toxic forms of mercury (Hg), the biomagnification of which is prevalent in the Arctic where apex predators such as polar bears (Ursus maritimus) can carry high loads. The maternal transfer of contaminants to offspring is a concern, as offspring may be particularly sensitive to the effects of environmental pollutants during early development. However, few studies of polar bears report on Hg in dependent young. We examined hair total Hg (THg) concentrations in 24 polar bear family groups in western Hudson Bay: mother, cub-of-the-year (COY), yearling, and 2 year old. THg concentrations increased with bear age, with COYs having lower concentrations than other offspring groups (p ≤ 0.008). Using AICc-based regression models, we found maternal THg to be positively related to body condition and litter size, while overall offspring THg was positively related to maternal body condition in addition to being dependent on the sex and age of the offspring. COY THg concentrations were positively related to maternal THg while also depending on the sex of the offspring. Considering our results, future studies in polar bear ecotoxicology are encouraged to include offspring of different ages and sexes.

Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies?

PubMed

Batcheller, April; Cardozo, Eden; Maguire, Marcy; DeCherney, Alan H; Segars, James H

2011-12-01

To review recent data regarding subtle, but widespread, epigenetic alterations in phenotypically normal offspring conceived by assisted reproductive technologies (ART) compared with offspring conceived in vivo. A PubMed computer search was performed to identify relevant articles. Research institution. Not applicable. None. Not applicable. Studies in animals indicate that in vitro culture may be associated with widespread alterations in imprinted genes compared with in vivo-conceived offspring. Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation, including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceived by ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ART also were noted in additional studies, which suggested that the diagnosis of infertility may explain the differences between in vivo-conceived and ART offspring. These data suggest that ART is associated with widespread epigenetic modifications in phenotypically normal children, and that these modifications may increase the risk of adverse cardiometabolic outcomes. Further research is needed to elucidate the possible relationship between ART, genome-wide alterations in imprinted genes, and their potential relevance to subtle cardiometabolic consequences reported in ART offspring. Published by Elsevier Inc.

[Psychopathological Profiles of Offspring of Subjects with Bipolar Disorder].

PubMed

Villa, Esteban Uribe; Briceño, Paola Gutiérrez; Palacio, Juan David; García, Jenny

2012-03-01

Bipolar Disorder (BD) has a high heritability and is more prevalent in first-degree relatives with family history. This makes the bipolar offspring (BO) an ideal study group to evaluate the natural history and the prodromal symptoms of this disorder. The main psychopathological findings for this group in various studies are described in this review. Articles comparing the psychopathology of bipolar offspring to either the offspring of other psychiatric patients or the offspring of healthy controls were reviewed. The reviewed studies showed that the BO group had higher rates of affective disorders when compared to the offspring of other psychiatric patients or the offspring of healthy controls. The high prevalence of anxiety disorders, ADHD, and disruptive behavior disorders in this population suggest that such disorders could be considered prodromes of mood disorders. The group of BO had a significantly higher risk of developing a wide range of psychiatric disorders besides BD. More longitudinal studies are needed to characterize this population at risk for BD and to elucidate the risk factors in the progression of this disorder. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Maternal exercise during pregnancy promotes physical activity in adult offspring

PubMed Central

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

2016-01-01

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

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.

Consumption of a high-salt diet by ewes during pregnancy alters nephrogenesis in 5-month-old offspring.

PubMed

Tay, S H; Blache, D; Gregg, K; Revell, D K

2012-11-01

Maternal nutrition during pregnancy can affect kidney development in the foetus, which may lead to adverse consequences in the mature kidney. It was expected that high-salt intake by pregnant ewes would lead to a reduction in foetal glomerular number but that the ovine kidney would adapt to maintain homoeostasis, in part by increasing the size of each glomerulus. Merino ewes that were fed either a control (1.5% NaCl) or high-salt (10.5% NaCl) diet during pregnancy, as well as their 5-month-old offspring, were subjected to a dietary salt challenge, and glomerular number and size and sodium excretion were measured. The high-salt offspring had 20% fewer glomeruli compared with the control offspring (P < 0.001), but they also had larger glomerular radii compared with the control offspring (P < 0.001). Consequently, the cross-sectional area of glomeruli was 18% larger in the high-salt offspring than in the control offspring (P < 0.05). There was no difference in the daily urinary sodium excretion between the two offspring groups (P > 0.05), although the high-salt offspring produced urine with a higher concentration of sodium. Our results demonstrated that maternal high-salt intake during pregnancy affected foetal nephrogenesis, altering glomerular number at birth. However, the ability to concentrate and excrete salt was not compromised, which indicates that the kidney was able to adapt to the reduction in the number of glomeruli.

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

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

PubMed

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

2018-06-04

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

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.

Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

PubMed Central

Cowley, Michael; Garfield, Alastair S.; Madon-Simon, Marta; Charalambous, Marika; Clarkson, Richard W.; Smalley, Matthew J.; Kendrick, Howard; Isles, Anthony R.; Parry, Aled J.; Carney, Sara; Oakey, Rebecca J.; Heisler, Lora K.; Moorwood, Kim; Wolf, Jason B.; Ward, Andrew

2014-01-01

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk. PMID:24586114

Time to take human embryo culture seriously.

PubMed

Sunde, Arne; Brison, Daniel; Dumoulin, John; Harper, Joyce; Lundin, Kersti; Magli, M Cristina; Van den Abbeel, Etienne; Veiga, Anna

2016-10-01

Is it important that end-users know the composition of human embryo culture media? We argue that there is as strong case for full transparency concerning the composition of embryo culture media intended for human use. Published data suggest that the composition of embryo culture media may influence the phenotype of the offspring. A review of the literature was carried out. Data concerning the potential effects on embryo development of culture media were assessed and recommendations for users made. The safety of ART procedures, especially with respect to the health of the offspring, is of major importance. There are reports from the literature indicating a possible effect of culture conditions, including culture media, on embryo and fetal development. Since the introduction of commercially available culture media, there has been a rapid development of different formulations, often not fully documented, disclosed or justified. There is now evidence that the environment the early embryo is exposed to can cause reprogramming of embryonic growth leading to alterations in fetal growth trajectory, birthweight, childhood growth and long-term disease including Type II diabetes and cardiovascular problems. The mechanism for this is likely to be epigenetic changes during the preimplantation period of development. In the present paper the ESHRE working group on culture media summarizes the present knowledge of potential effects on embryo development related to culture media, and makes recommendations. There is still a need for large prospective randomized trials to further elucidate the link between the composition of embryo culture media used and the phenotype of the offspring. We do not presently know if the phenotypic changes induced by in vitro embryo culture represent a problem for long-term health of the offspring. Published data indicate that there is a strong case for demanding full transparency concerning the compositions of and the scientific rationale behind the composition of embryo culture media. This work was funded by The European Society for Human Reproduction and Embryology. No competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Life-History Traits of Spodoptera frugiperda Populations Exposed to Low-Dose Bt Maize

PubMed Central

Sousa, Fernanda F.; Mendes, Simone M.; Santos-Amaya, Oscar F.; Araújo, Octávio G.; Oliveira, Eugenio E.

2016-01-01

Exposure to Bacillus thuringiensis (Bt) toxins in low- and moderate-dose transgenic crops may induce sublethal effects and increase the rate of Bt resistance evolution, potentially compromising control efficacy against target pests. We tested this hypothesis using the fall armyworm Spodoptera frugiperda, a major polyphagous lepidopteran pest relatively tolerant to Bt notorious for evolving field-relevant resistance to single-gene Bt maize. Late-instar larvae were collected from Bt Cry1Ab and non-Bt maize fields in five locations in Brazil, and their offspring was compared for survival, development, and population growth in rearing environment without and with Cry1Ab throughout larval development. Larval survival on Cry1Ab maize leaves varied from 20 to 80% among the populations. Larvae reared on Cry1Ab maize had seven-day delay in development time in relation to control larvae, and such delay was shorter in offspring of armyworms from Cry1Ab maize. Population growth rates were 50–70% lower for insects continuously exposed to Cry1Ab maize relative to controls, showing the population-level effect of Cry1Ab, which varied among the populations and prior exposure to Cry1Ab maize in the field. In three out of five populations, armyworms derived from Bt maize reared on Cry1Ab maize showed higher larval weight, faster larval development and better reproductive performance than the armyworms derived from non-Bt maize, and one of these populations showed better performance on both Cry1Ab and control diets, indicating no fitness cost of the resistance trait. Altogether, these results indicate that offspring of armyworms that developed on field-grown, single-gene Bt Cry1Ab maize had reduced performance on Cry1Ab maize foliage in two populations studied, but in other three populations, these offspring had better overall performance on the Bt maize foliage than that of the armyworms from non-Bt maize fields, possibly because of Cry1Ab resistance alleles in these populations. Implications of these findings for resistance management of S. frugiperda in Bt crops are discussed. PMID:27243977

Life-History Traits of Spodoptera frugiperda Populations Exposed to Low-Dose Bt Maize.

PubMed

Sousa, Fernanda F; Mendes, Simone M; Santos-Amaya, Oscar F; Araújo, Octávio G; Oliveira, Eugenio E; Pereira, Eliseu J G

2016-01-01

Exposure to Bacillus thuringiensis (Bt) toxins in low- and moderate-dose transgenic crops may induce sublethal effects and increase the rate of Bt resistance evolution, potentially compromising control efficacy against target pests. We tested this hypothesis using the fall armyworm Spodoptera frugiperda, a major polyphagous lepidopteran pest relatively tolerant to Bt notorious for evolving field-relevant resistance to single-gene Bt maize. Late-instar larvae were collected from Bt Cry1Ab and non-Bt maize fields in five locations in Brazil, and their offspring was compared for survival, development, and population growth in rearing environment without and with Cry1Ab throughout larval development. Larval survival on Cry1Ab maize leaves varied from 20 to 80% among the populations. Larvae reared on Cry1Ab maize had seven-day delay in development time in relation to control larvae, and such delay was shorter in offspring of armyworms from Cry1Ab maize. Population growth rates were 50-70% lower for insects continuously exposed to Cry1Ab maize relative to controls, showing the population-level effect of Cry1Ab, which varied among the populations and prior exposure to Cry1Ab maize in the field. In three out of five populations, armyworms derived from Bt maize reared on Cry1Ab maize showed higher larval weight, faster larval development and better reproductive performance than the armyworms derived from non-Bt maize, and one of these populations showed better performance on both Cry1Ab and control diets, indicating no fitness cost of the resistance trait. Altogether, these results indicate that offspring of armyworms that developed on field-grown, single-gene Bt Cry1Ab maize had reduced performance on Cry1Ab maize foliage in two populations studied, but in other three populations, these offspring had better overall performance on the Bt maize foliage than that of the armyworms from non-Bt maize fields, possibly because of Cry1Ab resistance alleles in these populations. Implications of these findings for resistance management of S. frugiperda in Bt crops are discussed.

The mother-offspring dyad: microbial transmission, immune interactions and allergy development.

PubMed

Jenmalm, M C

2017-12-01

The increasing prevalence of allergy in affluent countries may be caused by reduced intensity and diversity of microbial stimulation, resulting in abnormal postnatal immune maturation. Most studies investigating the underlying immunomodulatory mechanisms have focused on postnatal microbial exposure, for example demonstrating that the gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, it is also becoming increasingly evident that the maternal microbial environment during pregnancy is important in childhood immune programming, and the first microbial encounters may occur already in utero. During pregnancy, there is a close immunological interaction between the mother and her offspring, which provides important opportunities for the maternal microbial environment to influence the immune development of the child. In support of this theory, combined pre- and postnatal supplementations seem to be crucial for the preventive effect of probiotics on infant eczema. Here, the influence of microbial and immune interactions within the mother-offspring dyad on childhood allergy development will be discussed. In addition, how perinatal transmission of microbes and immunomodulatory factors from mother to offspring may shape appropriate immune maturation during infancy and beyond, potentially via epigenetic mechanisms, will be examined. Deeper understanding of these interactions between the maternal and offspring microbiome and immunity is needed to identify efficacious preventive measures to combat the allergy epidemic. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

PubMed

Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

2015-04-01

Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

The nature of the association between childhood ADHD and the development of bipolar disorder: a review of prospective high-risk studies.

PubMed

Duffy, Anne

2012-12-01

The author reviewed prospective longitudinal studies of the offspring of parents with bipolar disorder to inform our understanding of the nature of the association between childhood ADHD and the risk of developing bipolar disorder in adolescence and young adulthood. A literature review of published prospective cohort studies of the offspring of bipolar parents since 1985 was undertaken using a comprehensive search strategy in several electronic databases. The author provides a qualitative synthesis of results focusing on ADHD and the association with bipolar disorder in prospectively assessed high-risk offspring. These results are discussed in light of findings from other prospective epidemiological and clinical cohort studies. From the reviewed high-risk studies, evidence suggests that the clinical diagnosis of childhood ADHD is not a reliable predictor of the development of bipolar disorder. However, the author found evidence that symptoms of inattention may be part of a mixed clinical presentation during the early stages of evolving bipolar disorder in high-risk offspring, appearing alongside anxiety and depressive symptoms. The author also found preliminary evidence that childhood ADHD may form part of a neurodevelopmental phenotype in offspring at risk for developing a subtype of bipolar disorder unresponsive to lithium stabilization. While childhood ADHD does not appear to be part of the typical developmental illness trajectory of bipolar disorder, subjective problems with attention can form part of the early course, while neurodevelopmental abnormalities may be antecedents in a subgroup of high-risk children.

Reproductive phenology of a food-hoarding mast-seed consumer: resource- and density-dependent benefits of early breeding in red squirrels.

PubMed

Williams, Cory T; Lane, Jeffrey E; Humphries, Murray M; McAdam, Andrew G; Boutin, Stan

2014-03-01

The production of offspring by vertebrates is often timed to coincide with the annual peak in resource availability. However, capital breeders can extend the energetic benefits of a resource pulse by storing food or fat, thus relaxing the need for synchrony between energy supply and demand. Food-hoarding red squirrels (Tamiasciurus hudsonicus) breeding in the boreal forest are reliant on cones from a masting conifer for their nutrition, yet lactation is typically completed before the annual crop of cones is available for consumption such that peaks in energy supply and demand are not synchronized. We investigated the phenological response of red squirrels to annual variation in environmental conditions over a 20-year span and examined how intra- and inter-annual variation in the timing of reproduction affected offspring recruitment. Reproductive phenology was strongly affected by past resource availability with offspring born earlier in years following large cone crops, presumably because this affected the amount of capital available for reproduction. Early breeders had higher offspring survival and were more likely to renest following early litter loss when population density was high, perhaps because late-born offspring are less competitive in obtaining a territory when vacancies are limited. Early breeders were also more likely to renest after successfully weaning their first litter, but renesting predominantly occurred during mast years. Because of their increased propensity to renest and the higher survival rates of their offspring, early breeders contribute more recruits to the population but the advantage of early breeding depends on population density and resource availability.

Healthy offspring from freeze-dried mouse spermatozoa held on the International Space Station for 9 months

PubMed Central

Wakayama, Sayaka; Kamada, Yuko; Yamanaka, Kaori; Kohda, Takashi; Suzuki, Hiromi; Shimazu, Toru; Tada, Motoki N.; Osada, Ikuko; Nagamatsu, Aiko; Kamimura, Satoshi; Nagatomo, Hiroaki; Mizutani, Eiji; Ishino, Fumitoshi; Yano, Sachiko

2017-01-01

If humans ever start to live permanently in space, assisted reproductive technology using preserved spermatozoa will be important for producing offspring; however, radiation on the International Space Station (ISS) is more than 100 times stronger than that on Earth, and irradiation causes DNA damage in cells and gametes. Here we examined the effect of space radiation on freeze-dried mouse spermatozoa held on the ISS for 9 mo at –95 °C, with launch and recovery at room temperature. DNA damage to the spermatozoa and male pronuclei was slightly increased, but the fertilization and birth rates were similar to those of controls. Next-generation sequencing showed only minor genomic differences between offspring derived from space-preserved spermatozoa and controls, and all offspring grew to adulthood and had normal fertility. Thus, we demonstrate that although space radiation can damage sperm DNA, it does not affect the production of viable offspring after at least 9 mo of storage on the ISS. PMID:28533361

Healthy offspring from freeze-dried mouse spermatozoa held on the International Space Station for 9 months.

PubMed

Wakayama, Sayaka; Kamada, Yuko; Yamanaka, Kaori; Kohda, Takashi; Suzuki, Hiromi; Shimazu, Toru; Tada, Motoki N; Osada, Ikuko; Nagamatsu, Aiko; Kamimura, Satoshi; Nagatomo, Hiroaki; Mizutani, Eiji; Ishino, Fumitoshi; Yano, Sachiko; Wakayama, Teruhiko

2017-06-06

If humans ever start to live permanently in space, assisted reproductive technology using preserved spermatozoa will be important for producing offspring; however, radiation on the International Space Station (ISS) is more than 100 times stronger than that on Earth, and irradiation causes DNA damage in cells and gametes. Here we examined the effect of space radiation on freeze-dried mouse spermatozoa held on the ISS for 9 mo at -95 °C, with launch and recovery at room temperature. DNA damage to the spermatozoa and male pronuclei was slightly increased, but the fertilization and birth rates were similar to those of controls. Next-generation sequencing showed only minor genomic differences between offspring derived from space-preserved spermatozoa and controls, and all offspring grew to adulthood and had normal fertility. Thus, we demonstrate that although space radiation can damage sperm DNA, it does not affect the production of viable offspring after at least 9 mo of storage on the ISS.

Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood.

PubMed

Salomäki, Henriikka; Vähätalo, Laura H; Laurila, Kirsti; Jäppinen, Norma T; Penttinen, Anna-Maija; Ailanen, Liisa; Ilyasizadeh, Juan; Pesonen, Ullamari; Koulu, Markku

2013-01-01

The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. Metformin (300 mg/kg) or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase) and high fat diet (HFD-phase). At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a therapeutic agent during pregnancy.

Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring

PubMed Central

Ong, Z. Y.; Muhlhausler, B. S.

2011-01-01

Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal “junk-food” diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16±0.6 vs. 11±0.8 g/kg/d; females: 19±1.3 vs. 13±0.4 g/kg/d; P<0.01). mRNA expression of μ-opioid receptor (Mu) was 1.6-fold higher (P<0.01) and dopamine active transporter (DAT) was 2-fold lower (P<0.05) in JF offspring at 6 wk of age. By 3 mo, these differences were reversed, and Mu mRNA expression was 2.8-fold lower (P<0.01) and DAT mRNA expression was 1.9-fold higher (P<0.01) in the JF offspring. These findings suggest that perinatal exposure to high-fat, high-sugar diets results in altered development of the central reward system, resulting in increased fat intake and altered response of the reward system to excessive junk-food intake in postnatal life.—Ong, Z. Y., Muhlhausler, B. S. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. PMID:21427213

Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction

PubMed Central

Hillman, Sara; Peebles, Donald M.; Williams, David J.

2013-01-01

OBJECTIVE Fathers of low–birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth–restricted offspring were born. RESEARCH DESIGN AND METHODS We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who fathered normal–birth weight offspring (n = 77). All mothers were healthy, nonsmoking, and similar in age, BMI, ethnicity, and parity. Within 4 weeks of offspring birth, all fathers had measures of insulin resistance (HOMA index), blood pressure, waist circumference, endothelial function (flow-mediated dilatation), lipid profile, weight, and smoking habit. Comparison was made using multivariable logistical regression analysis. RESULTS Fathers of fetal growth–restricted offspring [mean (SD) 1.8th (2.2) customized birth centile] were more likely to have insulin resistance, hypertension, central adiposity, and endothelial dysfunction and to smoke cigarettes compared with fathers of normal grown offspring. After multivariable analysis, paternal insulin resistance and smoking remained different between the groups. Compared with fathers of normal grown offspring, men who fathered pregnancies affected by fetal growth restriction had an OR 7.68 (95% CI 2.63–22.40; P < 0.0001) of having a 1-unit higher log HOMA-IR value and 3.39 (1.26–9.16; P = 0.016) of being a smoker. CONCLUSIONS Men who recently fathered growth-restricted offspring have preclinical evidence of the insulin resistance syndrome and are more likely to smoke than fathers of normal grown offspring. Paternal lifestyle may influence heritable factors important for fetal growth. PMID:23315598

GROWTH AND DEVELOPMENT OF MICE OFFSPRING AFTER IRRADIATION IN UTERO WITH 2,450-MHZ MICROWAVES

EPA Science Inventory

Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm. sq. (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, ...

Prenatal low protein and postnatal high fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring

USDA-ARS?s Scientific Manuscript database

Maternal low protein diets during prenatal development contribute to the development of obesity and insulin resistance in offspring. In this study, obese-prone Sprague -Dawley rats were fed diets having either 8% (low protein, LP) or 20% (normal protein, NP) protein for 3-wk prior to conception and...

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.

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

PubMed

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

2015-08-06

Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory deficits in the offspring of dams with MTHFR deficiency or dietary deficiencies of critical methyl donors. We suggest that deficiencies in maternal one-carbon metabolism during pregnancy can contribute to hippocampal dysfunction in offspring through apoptosis or altered choline metabolism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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

The Interactive Effects of Ammonia and Microcystin on Life-History Traits of the Cladoceran Daphnia magna: Synergistic or Antagonistic?

PubMed Central

Yang, Zhou; Lü, Kai; Chen, Yafen; Montagnes, David J. S.

2012-01-01

The occurrence of Microcystis blooms is a worldwide concern that has caused numerous adverse effects on water quality and lake ecology. Elevated ammonia and microcystin concentrations co-occur during the degradation of Microcystis blooms and are toxic to aquatic organisms; we studied the relative and combined effects of these on the life history of the model organism Daphnia magna. Ammonia and microcystin-LR treatments were: 0, 0.366, 0.581 mg L−1 and 0, 10, 30, 100 µg L−1, respectively. Experiments followed a fully factorial design. Incubations were 14 d and recorded the following life-history traits: number of moults, time to first batch of eggs, time to first clutch, size at first batch of eggs, size at first clutch, number of clutches per female, number of offspring per clutch, and total offspring per female. Both ammonia and microcystin were detrimental to most life-history traits. Interactive effects of the toxins occurred for five traits: the time to first batch of eggs appearing in the brood pouch, time to first clutch, size at first clutch, number of clutches, and total offspring per female. The interactive effects of ammonia and microcystin appeared to be synergistic on some parameters (e.g., time to first eggs) and antagonistic on others (e.g., total offspring per female). In conclusion, the released toxins during the degradation of Microcystis blooms would result, according to our data, in substantially negative effect on D. magna. PMID:22403641

Association of parental obesity with concentrations of select systemic biomarkers in nonobese offspring: the Framingham Heart Study.

PubMed

Lieb, Wolfgang; Pencina, Michael J; Lanier, Katherine J; Tofler, Geoffrey H; Levy, Daniel; Fox, Caroline S; Wang, Thomas J; D'Agostino, Ralph B; Vasan, Ramachandran S

2009-01-01

Parental obesity is a risk factor for offspring obesity. It is unclear whether parental obesity also confers risk for obesity-associated conditions (e.g., a proinflammatory or prothrombotic state) in the absence of offspring obesity. We compared concentrations of multiple biomarkers representing distinct biological pathways (C-reactive protein [CRP], aldosterone, renin, B-type natriuretic peptide, NH(2)-terminal proatrial natriuretic peptide, fibrinogen, and plasminogen activator inhibitor-1) in nonobese Framingham Offspring Study participants with no parents (n = 665), one parent (n = 488), or two parents (n = 119) with obesity (BMI > or =30 kg/m(2)). Nonobese offspring with both parents with obesity had higher CRP levels (median 2.16 mg/l) than offspring with one parent (1.58 mg/l) or no parents (1.35 mg/l) with obesity. After multivariable adjustment, a nonlinear relationship with parental obesity became evident: compared with those without parental obesity, CRP levels were higher in offspring with two obese parents (P = 0.04) but not in offspring with only one obese parent (P = 0.76). Renin levels were more linearly related to parental obesity status, being significantly higher in offspring with one parent (P = 0.04) or two parents (P = 0.09) with obesity (P = 0.02 for trend). The other systemic biomarkers did not vary according to parental obesity status (all P > 0.05). Our findings suggest that offspring with a high risk of developing obesity have an altered biomarker profile, characterized by systemic inflammation and increased neurohormonal activity, even in the absence of obesity. This is consistent with the notion that parental obesity may confer an increased susceptibility to other adiposity-associated traits.

Maternal postpartum learned helplessness (LH) affects maternal care by dams and responses to the LH test in adolescent offspring.

PubMed

Kurata, Akiko; Morinobu, Shigeru; Fuchikami, Manabu; Yamamoto, Shigeto; Yamawaki, Shigeto

2009-06-01

It is known that the early environment affects the mental development of rodent and human offspring. However, it is not known specifically whether a postpartum depressive state influences the depressive state in offspring. Using learned helplessness (LH) in rats as an animal model of depression, we examined the influence of maternal postpartum LH on responses to the LH test of offspring. Dam rats were judged as LH or non-helpless (nLH) on postnatal days (PN) 2-3, and maternal behavior was recorded during PN2-14. On PN 45-46, offspring were subjected to the LH test. Plasma corticosterone (CORT) levels, hippocampal levels of glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA were measured before and after the LH test in offspring. Active nursing in LH dams was significantly lower than that in nLH dams. Susceptibility to LH in the offspring of LH dams was significantly higher than in those of nLH dams, and was negatively correlated with active nursing by LH dams. The GR mRNA levels before and after the LH test were lower in the offspring of LH dams than in those of nLH dams, and the reduced basal GR mRNA and protein might have resulted in the higher CORT response after the LH test. There was no significant difference in BDNF mRNA in the offspring of LH and nLH dams. These findings suggest that early postpartum LH decreased active nursing and increased depression-like behavior in the adolescent offspring via dysfunction of the hypothalamic-pituitary-adrenal axis.

The effects of maternal corticosterone levels on offspring behavior in fast- and slow-growth garter snakes (Thamnophis elegans).

PubMed

Robert, Kylie A; Vleck, Carol; Bronikowski, Anne M

2009-01-01

During embryonic development, viviparous offspring are exposed to maternally circulating hormones. Maternal stress increases offspring exposure to corticosterone and this hormonal exposure has the potential to influence developmental, morphological and behavioral traits of the resulting offspring. We treated pregnant female garter snakes (Thamnophis elegans) with low levels of corticosterone after determining both natural corticosterone levels in the field and pre-treatment levels upon arrival in the lab. Additional measurements of plasma corticosterone were taken at days 1, 5, and 10 during the 10-day exposure, which occurred during the last third of gestation (of 4-month gestation). These pregnant snakes were from replicate populations of fast- and slow-growth ecotypes occurring in Northern California, with concomitant short and long lifespans. Field corticosterone levels of pregnant females of the slow-growth ecotype were an order of magnitude higher than fast-growth dams. In the laboratory, corticosterone levels increased over the 10 days of corticosterone manipulation for animals of both ecotypes, and reached similar plateaus for both control and treated dams. Despite similar plasma corticosterone levels in treated and control mothers, corticosterone-treated dams produced more stillborn offspring and exhibited higher total reproductive failure than control dams. At one month of age, offspring from fast-growth females had higher plasma corticosterone levels than offspring from slow-growth females, which is opposite the maternal pattern. Offspring from corticosterone-treated mothers, although unaffected in their slither speed, exhibited changes in escape behaviors and morphology that were dependent upon maternal ecotype. Offspring from corticosterone-treated fast-growth females exhibited less anti-predator reversal behavior; offspring from corticosterone-treated slow-growth females exhibited less anti-predator tail lashing behavior.

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.

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:23991143

Female sticklebacks transfer information via eggs: effects of maternal experience with predators on offspring

PubMed Central

Giesing, Eric R.; Suski, Cory D.; Warner, Richard E.; Bell, Alison M.

2011-01-01

There is growing evidence that maternal experience influences offspring via non-genetic mechanisms. When female three-spined sticklebacks (Gasterosteus aculeatus) were exposed to the threat of predation, they produced larger eggs with higher cortisol content, which consumed more oxygen shortly after fertilization compared with a control group. As juveniles, the offspring of predator-exposed mothers exhibited tighter shoaling behaviour, an antipredator defence. We did not detect an effect of maternal exposure to predation risk on the somatic growth of fry. Altogether, we found that exposure to an ecologically relevant stressor during egg formation had several long-lasting consequences for offspring, some of which might be mediated by exposure to maternally derived cortisol. These results support the hypothesis that female sticklebacks might influence the development, growth and behaviour of their offspring via eggs to match their future environment. PMID:21068041

Maternal obesity and neurodevelopmental and psychiatric disorders in offspring

PubMed Central

Edlow, Andrea G.

2017-01-01

There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. PMID:27684946

Epigenetic Mechanisms and the Transgenerational Effects of Maternal Care

PubMed Central

Champagne, Frances A.

2009-01-01

The transmission of traits across generations has typically been attributed to the inheritance by offspring of genomic information from parental generations. However, recent evidence suggests that epigenetic mechanisms are capable of mediating this type of transmission. In the case of maternal care, there is evidence for the behavioral transmission of postpartum behavior from mothers to female offspring. The neuroendocrine and molecular mediators of this transmission have been explored in rats and implicate estrogen-oxytocin interactions and the differential methylation of hypothalamic estrogen receptors. These maternal effects can influence multiple aspects of neurobiology and behavior of offspring and this particular mode of inheritance is dynamic in response to environmental variation. In this review, evidence for the generational transmission of maternal care and the mechanisms underlying this transmission will be discussed as will the implications of this inheritance system for offspring development and for the transmission of environmental information from parents to offspring. PMID:18462782

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

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.

Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid composition in rat offspring.

PubMed

Toop, Carla R; Muhlhausler, Beverly S; O'Dea, Kerin; Gentili, Sheridan

2017-07-01

Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes. Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring. Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning. Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet. Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation. Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS-55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS-55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12 weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences.

PubMed

Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Otellin, Vladimir A; Aloisi, Anna Maria

2011-10-24

Prenatal stress strengthens tonic pain and provokes depression. The serotoninergic system is involved in these processes. We recently showed that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on depression and pain in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage, which is important for the correction of prenatal abnormalities. Maternal buspirone before restraint stress during the last week of pregnancy decreased the time of immobility in the forced swim test in the infant offspring. Prenatal stress increased formalin-induced pain in the second part of the time-course of the response to formalin in males of middle infancy but in the first part of the response in males of late infancy. The effect was reversed by maternal buspirone. Pain dominated in males of both middle and late infancy but the time-course of formalin pain in infant females revealed a slower development of the processes. The results show that the time-course of formalin-induced pain in infant rats reacts to prenatal stress in an age-dependent and sexually dimorphic manner. Our finding of opposite influences of prenatal stress and buspirone before prenatal stress on formalin-induced pain during the interphase indicates that functional maturity of the descending serotonergic inhibitory system occurs in late infancy males (11-day-olds), and 5-HT1A receptors participate in this process. The data provide evidence that maternal treatment with buspirone prior to stress during pregnancy alleviates depression-like and tonic pain-related behaviors in the infant offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy.

PubMed

Nathanielsz, Peter W; Ford, Stephen P; Long, Nathan M; Vega, Claudia C; Reyes-Castro, Luis A; Zambrano, Elena

2013-10-01

Maternal obesity is a global epidemic affecting both developed and developing countries. Human and animal studies indicate that maternal obesity adversely programs the development of offspring, predisposing them to chronic diseases later in life. Several mechanisms act together to produce these adverse health effects. There is a consequent need for effective interventions that can be used in the management of human pregnancy to prevent these outcomes. The present review analyzes the dietary and exercise intervention studies performed to date in both altricial and precocial animals, rats and sheep, with the aim of preventing adverse offspring outcomes. The results of these interventions present exciting opportunities to prevent, at least in part, adverse metabolic and other outcomes in obese mothers and their offspring. © 2013 International Life Sciences Institute.

Maternal vitamin D status and offspring bone fractures: prospective study over two decades in Aarhus City, Denmark.

PubMed

Petersen, Sesilje Bondo; Olsen, Sjurdur Frodi; Mølgaard, Christian; Granström, Charlotta; Cohen, Arieh; Vestergaard, Peter; Strøm, Marin

2014-01-01

Studies investigating the association between maternal vitamin D status and offspring bone mass measured by dual-energy X-ray absorptiometry (DXA) during childhood have shown conflicting results. We used occurrence of bone fractures up to the age of 18 as a measure reflecting offspring bone mass and related that to maternal vitamin D status. The Danish Fetal Origins 1988 Cohort recruited 965 pregnant women during 1988-89 at their 30th gestation week antenatal midwife visit. A blood sample was drawn and serum was stored, which later was analyzed for the concentration of 25-hydroxyvitamin D (25(OH)D) by the liquid chromatography coupled with a tandem mass spectrometric method (LC-MS/MS). Outcome was diagnosis of first time bone fractures extracted from the Danish National Patient Register. Vitamin D status was available for 850 women. The median (5th-95th percentile) 25(OH)D was 76.2 (23.0-152.1) nmol/l. During follow up 294 children were registered with at least one bone fracture diagnosis. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between maternal vitamin D status and first time bone fractures. However, there was a significantly increased hazard ratio (HR) during childhood for those who had maternal blood drawn in Dec/Jan/Feb compared with Jun/Jul/Aug (HR: 1.75, 95%CI: 1.11-2.74). Adjustment for vitamin D status strengthened this association (1.82, 1.12-2.97), which indicated a potential seasonal impact on offspring fractures independent of maternal vitamin D status. In a sensitivity analysis we found a borderline significant inverse association between continuous concentrations of 25(OH)D and offspring forearm fractures (P = 0.054). Overall, our results did not substantiate an association between maternal vitamin D status and offspring bone fractures. Further studies on this subject are needed, but the study populations must be large enough to allow for subdivision of fractures.

Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming.

PubMed

Vickers, M H; Reddy, S; Ikenasio, B A; Breier, B H

2001-08-01

Obesity and its related disorders are the most prevalent health problems in the Western world. Using the paradigm of fetal programming we developed a rodent model which displays the phenotype of obesity and metabolic disorders commonly observed in human populations. We apply maternal undernutrition throughout gestation, generating a nutrient-deprived intrauterine environment to induce fetal programming. Maternal undernutrition results in fetal growth retardation and in significantly decreased body weight at birth. Programmed offspring develop hyperphagia, obesity, hypertension, hyperleptinemia and hyperinsulinism during adult life and postnatal hypercaloric nutrition amplifies the metabolic abnormalities induced by fetal programming. The adipoinsular axis has been proposed as a primary candidate for linking the status of body fat mass to the function of the pancreatic beta-cells. We therefore investigated the relationship between circulating plasma concentrations of leptin and insulin and immunoreactivity in the endocrine pancreas for leptin and leptin receptor (OB-R) in genetically normal rats that were programmed to become obese during adult life. Virgin Wistar rats were time mated and randomly assigned to receive food either available ad libitum (AD group) or at 30% of the ad libitum available intake (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring (AD 6.13+/-0.04 g, UN 4.02+/-0.03 g, P<0.001). At weaning, offspring were assigned to one of two diets (a standard control diet or a hypercaloric diet consisting of 30% fat) for the remainder of the study. At the time of death (125 days of age), UN offspring had elevated (P<0.005) fasting plasma insulin (AD control 1.417+/-0.15 ng/ml, UN control 2.493+/-0.33 ng/ml, AD hypercaloric 1.70+/-0.17 ng/ml, UN hypercaloric 2.608+/-0.41 ng/ml) and leptin (AD control 8.8+/-1.6 ng/ml, UN control 14.32+/-1.9 ng/ml, AD hypercaloric 15.11+/-1.8 ng/ml, UN hypercaloric 30.18+/-5.3 ng/ml) concentrations, which were further increased (P<0.05) by postnatal hypercaloric nutrition. The elevated plasma insulin and leptin concentrations were paralleled by increased immunolabeling for leptin in the peripheral cells of the pancreatic islets. Dual immunofluorescence histochemistry for somatostatin and leptin revealed that leptin was co-localized in the pancreatic delta-cells. OB-R immunoreactivity was evenly distributed throughout the pancreatic islets and was not changed by programming nor hypercaloric nutrition. Our data suggest that reduced substrate supply during fetal development can trigger permanent dysregulation of the adipoinsular feedback system leading to hyperleptinemia, hyperinsulinism and compensatory leptin production by pancreatic delta-cells in a further attempt to reduce insulin hypersecretion in the progression to adipogenic diabetes.

Parental care mitigates carry-over effects of poor early conditions on offspring growth

USGS Publications Warehouse

Auer, Sonya K.; Martin, Thomas E.

2017-01-01

Poor developmental conditions can have long-lasting negative effects on offspring phenotypes, but impacts often differ among species. Contrasting responses may reflect disparities in experimental protocols among single-species studies or inherent differences among species in their sensitivity to early conditions and/or ability to mitigate negative impacts. We used a common experimental protocol to assess and compare the role of parental care in mitigating effects of poor early conditions on offspring among 4 sympatric bird species in the wild. We experimentally induced low incubation temperatures and examined effects on embryonic developmental rates, hatching success, nestling growth rates, and parental responses. We examined the generality of these effects across 4 species that differ in their phylogenetic history, breeding ecology, and life histories. We found that cooling led to delayed hatching in all species, but carry-over effects on offspring differed among species. Parents of some but not all species increased their offspring provisioning rates in response to experimental cooling with critical benefits for offspring growth rates. Our study shows for the first time that species exhibit clear differences in the degree to which they are affected by poor early conditions. Observed differences among species demonstrate that parental care is a critical mechanism for mitigating potential negative effects on offspring and suggest that parental responses may be constrained to varying degrees by ecology and life histories.

Maternal Dietary Patterns during Pregnancy in Relation to Offspring Forearm Fractures: Prospective Study from the Danish National Birth Cohort

PubMed Central

Petersen, Sesilje B.; Rasmussen, Morten A.; Olsen, Sjurdur F.; Vestergaard, Peter; Mølgaard, Christian; Halldorsson, Thorhallur I.; Strøm, Marin

2015-01-01

Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996–2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (<16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01–1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dietary patterns showed no associations and neither did supplementary analyses of macro- and micronutrients or single food groups, except for the intake of artificially sweetened soft drinks, which was positively associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future research. PMID:25849947

Assessing and comparison of different machine learning methods in parent-offspring trios for genotype imputation.

PubMed

Mikhchi, Abbas; Honarvar, Mahmood; Kashan, Nasser Emam Jomeh; Aminafshar, Mehdi

2016-06-21

Genotype imputation is an important tool for prediction of unknown genotypes for both unrelated individuals and parent-offspring trios. Several imputation methods are available and can either employ universal machine learning methods, or deploy algorithms dedicated to infer missing genotypes. In this research the performance of eight machine learning methods: Support Vector Machine, K-Nearest Neighbors, Extreme Learning Machine, Radial Basis Function, Random Forest, AdaBoost, LogitBoost, and TotalBoost compared in terms of the imputation accuracy, computation time and the factors affecting imputation accuracy. The methods employed using real and simulated datasets to impute the un-typed SNPs in parent-offspring trios. The tested methods show that imputation of parent-offspring trios can be accurate. The Random Forest and Support Vector Machine were more accurate than the other machine learning methods. The TotalBoost performed slightly worse than the other methods.The running times were different between methods. The ELM was always most fast algorithm. In case of increasing the sample size, the RBF requires long imputation time.The tested methods in this research can be an alternative for imputation of un-typed SNPs in low missing rate of data. However, it is recommended that other machine learning methods to be used for imputation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The mechanism underlying dibutyl phthalate induced shortened anogenital distance and hypospadias in rats.

PubMed

Li, Ning; Chen, Xuyong; Zhou, Xuefeng; Zhang, Wen; Yuan, Jiyan; Feng, Jiexiong

2015-12-01

The purpose of this study was to investigate the mechanism of dibutyl phthalate (DBP) induced hypospadias and shortened anogenital distance (AGD). AGD, hypospadias, and cryptorchidism incidence was observed in male offspring of DBP treated pregnant Wistar rats. Testicular development and testosterone levels of normal and DBP-treated rat embryos were compared. Male offspring of 300mg and 900mg DBP-treated pregnant Wistar rats exhibited shortened average AGD compared with the control group. A 22.7% hypospadias incidence was observed in the 300mg group, but no offspring with cryptorchidism were identified. In the 900mg group, hypospadias and cryptorchidism incidence reached 43.5% and 17.4%, respectively. Between E15.5 and E17.5, the 300mg group exhibited delayed testicular development and testosterone secretion. However, testicular development and testosterone secretion subsequently recovered. The 300mg treated and control groups had similar measures after E19.5. Contrastingly, testicular development and testosterone secretion were significantly diminished throughout development in the 900mg group. Exogenous testosterone partially counteracted DBP-induced changes in the reproductive organs of male offspring of DBP-treated rats. High-dose DBP exposure may induce testicular dysgenesis in rat embryos. Additionally, low-dose DBP may delay testicular development and testosterone secretion during urethral development. This disruption may result in hypospadias. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of Sensory Receptors in Skeletal Muscle

NASA Technical Reports Server (NTRS)

DeSantis, Mark

2000-01-01

The two major goals for this project is to (1) examine the hindlimb walking pattern of offspring from the Flight dams as compared with offspring of the ground control groups from initiation of walking up to two months thereafter; and (2) examine skeletal muscle.

Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring.

PubMed

Saad, M I; Abdelkhalek, T M; Haiba, M M; Saleh, M M; Hanafi, M Y; Tawfik, S H; Kamel, M A

2016-06-01

The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity.

PubMed

Soeda, Junpei; Cordero, Paul; Li, Jiawei; Mouralidarane, Angelina; Asilmaz, Esra; Ray, Shuvra; Nguyen, Vi; Carter, Rebeca; Novelli, Marco; Vinciguerra, Manlio; Poston, Lucilla; Taylor, Paul D; Oben, Jude A

2017-06-01

We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype. UPR signalling pathways (IREα, PERK, ATF6) and their downstream regulators showed different basal rhythmicity, which was modified in offspring exposed to obesogenic diet and maternal programming. The double obesogenic hit increased liver apoptosis measured by TUNEL staining, active caspase-3 and phospho-JNK and GRP78 promoter methylation levels. This study demonstrates that hepatic UPR is rhythmically activated. The combination of maternal obesity (MO) and obesogenic diets in offspring triggered altered UPR rhythmicity, DNA methylation and cellular apoptosis.

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.

Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II-the developmental pattern of neurons in relation to oxidative stress and antioxidant defense system.

PubMed

Ahmed, O M; Ahmed, R G; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M

2012-10-01

Excessive concentrations of free radicals in the developing brain may lead to neurons maldevelopment and neurons damage and death. Thyroid hormones (THs) states play an important role in affecting the modulation of oxidative stress and antioxidant defense system. Thus, the objective of this study was to clarify the effect of hypothyroidism and hyperthyroidism in rat dams on the neurons development of different brain regions of their offspring at several postnatal weeks in relation to changes in the oxidative stress and antioxidant defense system. The adult female rats were administered methimazole (MMI) in drinking water (0.02% w/v) from gestation day 1 to lactation day 21 to induce hypothyroidism and exogenous thyroxine (T4) in drinking water (0.002% w/v) beside intragastric incubation of 50--200 T4 μg/kg body weight (b. wt.) to induce hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and total triiodothyronine (TT3) levels were detectably increased at day 10 post-partum than those at day 10 of pregnancy. Free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations in normal offspring were elevated at first, second and third postnatal weeks in an age-dependent manner. In hypothyroid group, a marked depression was observed in sera of dam TT3 and TT4 as well as offspring FT3, FT4 and GH, while there was a significant increase in TSH level with the age progress. The reverse pattern to latter state was recorded in hyperthyroid group. Concomitantly, in control offspring, the rate of neuron development in both cerebellar and cerebral cortex was increased in its density and complexity with age progress. This development may depend, largely, on THs state. Both maternal hypothyroidism and hyperthyroidism caused severe growth retardation in neurons of these regions of their offspring from the first to third weeks. Additionally, in normal offspring, seven antioxidant enzymes, four non-enzymatic antioxidants and one oxidative stress marker (lipid peroxidation, LPO) followed a synchronized course of alterations in cerebrum, cerebellum and medulla oblongata. In both thyroid states, the oxidative damage has been demonstrated by the increased LPO and inhibition of enzymatic and non-enzymatic antioxidants in most examined ages and brain regions. These disturbances in the antioxidant defense system led to deterioration in the neuronal maturation and development. In conclusion, it can be suggested that the maldevelopment of neurons and dendrites in different brain regions of offspring of hypothyroid and hyperthyroid mother rat dams may be attributed, at least in part, to the excess oxidative stress and deteriorated antioxidant defense system in such conditions. Published by Elsevier Ltd.

Childhood adversity, parental vulnerability and disorder: examining inter-generational transmission of risk.

PubMed

Bifulco, A; Moran, P M; Ball, C; Jacobs, C; Baines, R; Bunn, A; Cavagin, J

2002-11-01

An investigation of intergenerational factors associated with psychiatric disorder in late adolescence/early adulthood was undertaken to differentiate influences from maternal disorder, maternal poor psychosocial functioning and poor parenting, on offspring. The sample comprised an intensively studied series of 276 mother-offspring pairs in a relatively deprived inner-city London area with high rates of lone parenthood and socio-economic disadvantage. The paired sample was collected over two time periods: first a consecutively screened series of mothers and offspring in 1985-90 (n = 172 pairs) and second a 'vulnerable' series of mothers and offspring in 1995-99 (n = 104 pairs). The vulnerable mothers were selected for poor interpersonal functioning and/or low self-esteem and the consecutive series were used for comparison. Rates of childhood adversity and disorder in the offspring were examined in the two groups. Maternal characteristics including psychosocial vulnerability and depression were then examined in relation to risk transmission. Offspring of vulnerable mothers had a fourfold higher rate of yearly disorder than those in the comparison series (43% vs. 11%, p < .001). They were twice as likely as those in the comparison series to have experienced childhood adversity comprising either severe neglect, physical or sexual abuse before age 17. Physical abuse, in particular, perpetrated either by mother or father/surrogate father was significantly raised in the vulnerable group. Analysis of the combined series showed that maternal vulnerability and neglect/abuse of offspring provided the best model for offspring disorder. Maternal history of depression had no direct effect on offspring disorder; its effects were entirely mediated by offspring neglect/abuse. Maternal childhood adversity also had no direct effect. Results are discussed in relation to psychosocial models of risk transmission for disorder. Maternal poor psychosocial functioning needs to be identified as a factor requiring intervention in order to stem escalation of risk across generations.

Pre-breeding food restriction promotes the optimization of parental investment in house mice, Mus musculus.

PubMed

Dušek, Adam; Bartoš, Luděk; Sedláček, František

2017-01-01

Litter size is one of the most reliable state-dependent life-history traits that indicate parental investment in polytocous (litter-bearing) mammals. The tendency to optimize litter size typically increases with decreasing availability of resources during the period of parental investment. To determine whether this tactic is also influenced by resource limitations prior to reproduction, we examined the effect of experimental, pre-breeding food restriction on the optimization of parental investment in lactating mice. First, we investigated the optimization of litter size in 65 experimental and 72 control families (mothers and their dependent offspring). Further, we evaluated pre-weaning offspring mortality, and the relationships between maternal and offspring condition (body weight), as well as offspring mortality, in 24 experimental and 19 control families with litter reduction (the death of one or more offspring). Assuming that pre-breeding food restriction would signal unpredictable food availability, we hypothesized that the optimization of parental investment would be more effective in the experimental rather than in the control mice. In comparison to the controls, the experimental mice produced larger litters and had a more selective (size-dependent) offspring mortality and thus lower litter reduction (the proportion of offspring deaths). Selective litter reduction helped the experimental mothers to maintain their own optimum condition, thereby improving the condition and, indirectly, the survival of their remaining offspring. Hence, pre-breeding resource limitations may have facilitated the mice to optimize their inclusive fitness. On the other hand, in the control females, the absence of environmental cues indicating a risky environment led to "maternal optimism" (overemphasizing good conditions at the time of breeding), which resulted in the production of litters of super-optimal size and consequently higher reproductive costs during lactation, including higher offspring mortality. Our study therefore provides the first evidence that pre-breeding food restriction promotes the optimization of parental investment, including offspring number and developmental success.

Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

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

Johri, Ashu; Yadav, Sanjay; Dhawan, Alok

2008-08-15

ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD{sub 50}; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increasemore » in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics.« less

Maternal malnutrition and offspring sex determine juvenile obesity and metabolic disorders in a swine model of leptin resistance.

PubMed

Barbero, Alicia; Astiz, Susana; Lopez-Bote, Clemente J; Perez-Solana, Maria L; Ayuso, Miriam; Garcia-Real, Isabel; Gonzalez-Bulnes, Antonio

2013-01-01

The present study aimed to determine, in a swine model of leptin resistance, the effects of type and timing of maternal malnutrition on growth patterns, adiposity and metabolic features of the progeny when exposed to an obesogenic diet during their juvenile development and possible concomitant effects of the offspring sex. Thus, four groups were considered. A CONTROL group involved pigs born from sows fed with a diet fulfilling their daily maintenance requirements for pregnancy. The treated groups involved the progeny of females fed with the same diet but fulfilling either 160% or 50% of pregnancy requirements during the entire gestation (OVERFED and UNDERFED, respectively) or 100% of requirements until Day 35 of pregnancy and 50% of such amount from Day 36 onwards (LATE-UNDERFED). OVERFED and UNDERFED offspring were more prone to higher corpulence and fat deposition from early postnatal stages, during breast-feeding; adiposity increased significantly when exposed to obesogenic diets, especially in females. The effects of sex were even more remarkable in LATE-UNDERFED offspring, which had similar corpulence to CONTROL piglets; however, females showed a clear predisposition to obesity. Furthermore, the three groups of pigs with maternal malnutrition showed evidences of metabolic syndrome and, in the case of individuals born from OVERFED sows, even of insulin resistance and the prodrome of type-2 diabetes. These findings support the main role of early nutritional programming in the current rise of obesity and associated diseases in ethnics with leptin resistance.

Inbred guinea pig model of intrauterine infection with cytomegalovirus.

PubMed

Griffith, B P; McCormick, S R; Booss, J; Hsiung, G D

1986-01-01

Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.

Maternal Malnutrition and Offspring Sex Determine Juvenile Obesity and Metabolic Disorders in a Swine Model of Leptin Resistance

PubMed Central

Barbero, Alicia; Astiz, Susana; Lopez-Bote, Clemente J.; Perez-Solana, Maria L.; Ayuso, Miriam; Garcia-Real, Isabel; Gonzalez-Bulnes, Antonio

2013-01-01

The present study aimed to determine, in a swine model of leptin resistance, the effects of type and timing of maternal malnutrition on growth patterns, adiposity and metabolic features of the progeny when exposed to an obesogenic diet during their juvenile development and possible concomitant effects of the offspring sex. Thus, four groups were considered. A CONTROL group involved pigs born from sows fed with a diet fulfilling their daily maintenance requirements for pregnancy. The treated groups involved the progeny of females fed with the same diet but fulfilling either 160% or 50% of pregnancy requirements during the entire gestation (OVERFED and UNDERFED, respectively) or 100% of requirements until Day 35 of pregnancy and 50% of such amount from Day 36 onwards (LATE-UNDERFED). OVERFED and UNDERFED offspring were more prone to higher corpulence and fat deposition from early postnatal stages, during breast-feeding; adiposity increased significantly when exposed to obesogenic diets, especially in females. The effects of sex were even more remarkable in LATE-UNDERFED offspring, which had similar corpulence to CONTROL piglets; however, females showed a clear predisposition to obesity. Furthermore, the three groups of pigs with maternal malnutrition showed evidences of metabolic syndrome and, in the case of individuals born from OVERFED sows, even of insulin resistance and the prodrome of type-2 diabetes. These findings support the main role of early nutritional programming in the current rise of obesity and associated diseases in ethnics with leptin resistance. PMID:24205230

Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats.

PubMed

Michaels, Clifford C; Holtzman, Stephen G

2007-04-01

Early-life stress has been identified as a risk factor in the development of a host of disorders, including substance abuse; however the link between early postnatal stress and changes in measures of reward has not been thoroughly researched. The current study had two main objectives: 1) to determine the impact of maternal separation (an animal model of early-life stress) on the consumption of 10% and 2.5% sucrose solutions by Long-Evans rat dams and male and female offspring, and 2) to determine the effect of the opioid antagonist naltrexone (0.1-3.0 mg/kg) on drinking by each of those groups. Dam-pup separations occurred for varying lengths of time during the first two postnatal weeks. In Experiment 1, a two-bottle choice test (sucrose solution vs. water) was administered across five days to both nonhandled (NH) and maternally-separated (MS) offspring as adults and to dams 2-4 weeks post-weaning. In Experiment 2, naltrexone was administered prior to two-bottle choice tests. MS males and the dams of MS litters exhibited increased intake of total fluid and sucrose solutions, whereas results from females were less consistent. Naltrexone elicited a greater decrease in fluid intake and sucrose intake in male MS offspring compared to male NH offspring. These results indicate that early postnatal stress alters both sucrose consumption, a non-drug measure of reward, and apparently the brain opioid systems that mediate naltrexone-induced drinking suppression.

High risk of neonatal complications in children of mothers with gestational diabetes mellitus in their first pregnancy.

PubMed

Wielandt, Hanne Benedicte; Schønemann-Rigel, Helena; Holst, Charlotte Blunck; Fenger-Grøn, Jesper

2015-06-01

THE study presents the neonatal outcome from a cohort of women with gestational diabetes mellitus (GDM) in their first pregnancy. During a five-year period (2009-2013), a prospective follow-up study was performed at the Department of Gynaecology and Obstetrics, Lillebaelt Hospital - Kolding. The study included 535 pregnant women diagnosed with GDM. A study population of nulliparous GDM patients was sampled, and during the period from 1 January 2010 to 1 March 2013, a total of 137 women delivered for the first time. The present study population considers the 131 offspring, excluding six pairs of twins. The overwhelming majority of the offspring had a birth weight within the normal range and only six (4.6%) were large for gestational age. There were 95 (72.5%) vaginal deliveries, whereas 36 (27.5%) were born by caesarean section (CS). Nearly half of the 25 nulliparous GDM patients with a body mass index ≥ 35 kg/m² delivered by CS - six by emergency CS and three by planned CS. A total of 20 neonates (15.3%) developed neonatal hypoglycaemia and four (3.1%) had an Apgar score < 7 after 5 min. A total of 25 (19.1%) among the offspring were admitted to the neonatal intensive care unit. The present study supports the notion of high-risk pregnancy among GDM patients. Compared with nulliparous in general, the offspring were more likely to be delivered by emergency CS. Despite the prophylactic procedures, one in six had neonatal hypoglycaemia.

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

Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes.

PubMed

Mainigi, Monica; Rosenzweig, Jason M; Lei, Jun; Mensah, Virginia; Thomaier, Lauren; Talbot, C Conover; Olalere, Devvora; Ord, Teri; Rozzah, Rayyan; Johnston, Michael V; Burd, Irina

2016-06-01

While live births resulting from assisted reproductive technology (ART) exceed 1% of total births annually, the effect of ART on fetal development is not well understood. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. In order to isolate the peri-implantation environment and its effects on brain development, we utilized a mouse model with and without superovulation and examined the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P < .05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P < .05). In order to examine potential pathways leading to these changes, we measured messenger RNA and microRNA (miRNA) expression in fetal brains at E18.5. Microarray analysis found that miRNAs miR-122, miR-144, and miR-211, involved in regulation of neuronal migration and differentiation, were downregulated in brains of offspring exposed to a superovulated environment(P < .05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring. © The Author(s) 2015.

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.

Parental identity influences progeny responses to incubation thermal stress in sockeye salmon Onchorhynchus nerka.

PubMed

Burt, J M; Hinch, S G; Patterson, D A

2012-02-01

The influence of individual parentage on progeny responses to early developmental temperature stress was examined in a cross-fertilization experiment using sockeye salmon Oncorhynchus nerka. Differences in survival, hatch timing and size were examined among five paternally linked and five maternally linked offspring families (Weaver Creek population, British Columbia, Canada) incubated at 12, 14 and 16° C from just after fertilization to hatch. Mean embryonic survival was significantly lower at 14 and 16° C; however, offspring families had substantially different survival responses across the thermal gradient (crossing reaction norms). Within temperature treatments, substantial variation in embryonic survival, alevin mass, time-to-hatch and hatch duration were attributable to family identity; however, most traits were governed by significant temperature-family interactions. For embryonic survival, large differences between families at 16° C were due to both female and male spawner influence, whereas inter-family differences were obscured at 14° C (high intra-family variation), and minimal at 12° C (only maternal influence detected). Despite post-hatch rearing under a common cool thermal regime, persistent effects of both temperature and parentage were detected in alevin and 3 week-old fry. Collectively, these findings highlight the crucial role that parental influences on offspring may have in shaping future selection within salmonid populations exposed to elevated thermal regimes. An increased understanding of parental and temperature influences and their persistence in early development will be essential to developing a more comprehensive view of population spawning success and determining the adaptive capacity of O. nerka populations in the face of environmental change. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner.

PubMed

Paternain, L; de la Garza, A L; Batlle, M A; Milagro, F I; Martínez, J A; Campión, J

2013-03-01

Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-γ coactivator1-α (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intake.

Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice.

PubMed

Sugawara, Norio; Nakai, Kunihiko; Nakamura, Tomoyuki; Ohba, Takashi; Suzuki, Keita; Kameo, Satomi; Satoh, Chieko; Satoh, Hiroshi

2006-05-01

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.

Developmental cigarette smoke exposure II: Hippocampus proteome and metabolome profiles in adult offspring.

PubMed

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

2016-10-01

Exposure to cigarette smoke during development is linked to neurodevelopmental delays and cognitive impairment including impulsivity, attention deficit disorder, and lower IQ. Utilizing a murine experimental model of "active" inhalation exposure to cigarette smoke spanning the entirety of gestation and through human third trimester equivalent hippocampal development [gestation day 1 (GD1) through postnatal day 21 (PD21)], we examined hippocampus proteome and metabolome alterations present at a time during which developmental cigarette smoke exposure (CSE)-induced behavioral and cognitive impairments are evident in adult animals from this model system. At six month of age, carbohydrate metabolism and lipid content in the hippocampus of adult offspring remained impacted by prior exposure to cigarette smoke during the critical period of hippocampal ontogenesis indicating limited glycolysis. These findings indicate developmental CSE-induced systemic glucose availability may limit both organism growth and developmental trajectory, including the capacity for learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

An ecologically relevant guinea pig model of fetal behavior.

PubMed

Bellinger, S A; Lucas, D; Kleven, G A

2015-04-15

The laboratory guinea pig, Cavia porcellus, shares with humans many similarities during pregnancy and prenatal development, including precocial offspring and social dependence. These similarities suggest the guinea pig as a promising model of fetal behavioral development as well. Using innovative methods of behavioral acclimation, fetal offspring of female IAF hairless guinea pigs time mated to NIH multicolored Hartley males were observed longitudinally without restraint using noninvasive ultrasound at weekly intervals across the 10 week gestation. To ensure that the ultrasound procedure did not cause significant stress, salivary cortisol was collected both before and after each observation. Measures of fetal spontaneous movement and behavioral state were quantified from video recordings from week 3 through the last week before birth. Results from prenatal quantification of Interlimb Movement Synchrony and state organization reveal guinea pig fetal development to be strikingly similar to that previously reported for other rodents and preterm human infants. Salivary cortisol readings taken before and after sonography did not differ at any observation time point. These results suggest this model holds translational promise for studying the prenatal mechanisms of neurobehavioral development, including those that may result from adverse events. Because the guinea pig is a highly social mammal with a wide range of socially oriented vocalizations, this model may also have utility for studying the prenatal origins and trajectories of developmental disabilities with social-emotional components, such as autism. Copyright © 2015 Elsevier B.V. All rights reserved.

An ecologically relevant guinea pig model of fetal behavior

PubMed Central

Bellinger, S. A.; Lucas, D.; Kleven, G. A.

2015-01-01

The laboratory guinea pig, Cavia porcellus, shares with humans many similarities during pregnancy and prenatal development, including precocial offspring and social dependence. These similarities suggest the guinea pig as a promising model of fetal behavioral development as well. Using innovative methods of behavioral acclimation, fetal offspring of female IAF hairless guinea pigs time mated to NIH multi-colored Hartley males were observed longitudinally without restraint using noninvasive ultrasound at weekly intervals across the 10 week gestation. To insure that the ultrasound procedure did not cause significant stress, salivary cortisol was collected both before and after each observation. Measures of fetal spontaneous movement and behavioral state were quantified from video recordings from week 3 through the last week before birth. Results from prenatal quantification of Interlimb Movement Synchrony and state organization reveal guinea pig fetal development to be strikingly similar to that previously reported for other rodents and preterm human infants. Salivary cortisol readings taken before and after sonography did not differ at any observation time point. These results suggest this model holds translational promise for studying the prenatal mechanisms of neurobehavioral development, including those that may result from adverse events. Because the guinea pig is a highly social mammal with a wide range of socially oriented vocalizations, this model may also have utility for studying the prenatal origins and trajectories of developmental disabilities with social-emotional components, such as autism. PMID:25655512

Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function

PubMed Central

Connor, K L; Vickers, M H; Beltrand, J; Meaney, M J; Sloboda, D M

2012-01-01

We have previously reported that offspring of mothers fed a high fat (HF) diet during pregnancy and lactation enter puberty early and are hyperleptinaemic, hyperinsulinaemic and obese as adults. Poor maternal care and bonding can also impact offspring development and disease risk. We therefore hypothesized that prenatal nutrition would affect maternal care and that an interaction may exist between a maternal HF diet and maternal care, subsequently impacting on offspring phenotype. Wistar rats were mated and randomized to control dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Maternal care was assessed by observing maternal licking and grooming of pups between postnatal day (P)3 and P8. Postweaning (P22), offspring were fed a control (–con) or HF (–hf) diet. From P27, pubertal onset was assessed. At ∼P105 oestrous cyclicity was investigated. Maternal HF diet reduced maternal care; HF-fed mothers licked and groomed pups less than CON dams. Maternal fat:lean ratio was higher in HF dams at weaning and was associated with higher maternal plasma leptin and insulin concentrations, but there was no effect of maternal care on fat:lean ratio or maternal hormone levels. Both female and male offspring of HF dams were lighter from birth to P11 than offspring of CON dams, but by P19, HF offspring were heavier than controls. Prepubertal retroperitoneal fat mass was greater in pups from HF-fed dams compared to CON and was associated with elevated circulating leptin concentrations in females only, but there was neither an effect of maternal care, nor an interaction between maternal diet and care on prepubertal fat mass. Pups from HF-fed dams went into puberty early and this effect was exacerbated by a postweaning HF diet. Maternal and postweaning HF diets independently altered oestrous cyclicity in females: female offspring of HF-fed mothers were more likely to have prolonged or persistent oestrus, whilst female offspring fed a HF diet postweaning were more likely to have irregular oestrous cycles and were more likely to have prolonged or persistent oestrus. These data indicate that maternal HF nutrition during pregnancy and lactation results in a maternal obese phenotype and has significant impact on maternal care during lactation. Maternal and postweaning nutritional signals, independent of maternal care, alter offspring body fat pre-puberty and female reproductive function in adulthood, which may be associated with advanced ovarian ageing and altered fertility. PMID:22411006

Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation.

PubMed

Bai, S Y; Briggs, D I; Vickers, M H

2012-10-01

An adverse prenatal environment may induce long-term metabolic consequences, in particular hypertension and cardiovascular disease. A maternal low-protein (LP) diet is well known to result in increased blood pressure (BP) in offspring. Choline has been shown to have direct BP-reducing effects in humans and animals. It has been suggested that endogenous choline synthesis via phosphatidylcholine is constrained during maternal LP exposure. The present study investigates the effect of choline supplementation to mothers fed a LP diet during pregnancy on systolic BP (SBP) in offspring as measured by tail-cuff plethysmography. Wistar rats were assigned to one of three diets to be fed ad libitum throughout pregnancy: (1) control diet (CONT, 20% protein); (2) an LP diet (9% protein); and (3) LP supplemented with choline (LP + C). Dams were fed the CONT diet throughout lactation and offspring were fed the CONT diet from weaning for the remainder of the trial. At postnatal day 150, SBP and retroperitoneal fat mass was significantly increased in LP offspring compared with CONT animals and was normalized in LP + C offspring. Effects of LP + C reduction in SBP were similar in both males and females. Plasma choline and phosphatidylcholine concentrations were not different across treatment groups, but maternal choline supplementation resulted in a significant reduction in homocysteine concentrations in LP + C offspring compared with LP and CONT animals. The present trial shows for the first time that maternal supplementation with dietary choline during periods of LP exposure can normalize increased SBP and fat mass observed in offspring in later life.

Differences in the effective population sizes of males and females do not require differences in their distribution of offspring number.

PubMed

Mendez, Fernando L

2017-04-01

Difference in male and female effective population sizes has, at times, been attributed to both sexes having unequal variance in their number of offspring. Such difference is paralleled by the relative effective sizes of autosomes, sex chromosomes, and mitochondrial DNA. I develop a simple framework to calculate the inbreeding effective population sizes for loci with different modes of inheritance. In this framework, I separate the effects due to mating strategy and those due to genetic transmission. I then show that, in addition to differences in the variance in offspring number, skew in the male/female effective sizes can also be caused by family composition. This approach can be used to illustrate the effect of induced behaviors on the relative male and female effective population sizes. In particular, I show the impact of the one-child policy formerly implemented in the People's Republic of China on the relative male and female effective population sizes. Furthermore, I argue that, under some strong constraints on family structure, the concepts of male and female effective population sizes are invalid. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Coalescent Processes with Skewed Offspring Distributions and Nonequilibrium Demography.

PubMed

Matuszewski, Sebastian; Hildebrandt, Marcel E; Achaz, Guillaume; Jensen, Jeffrey D

2018-01-01

Nonequilibrium demography impacts coalescent genealogies leaving detectable, well-studied signatures of variation. However, similar genomic footprints are also expected under models of large reproductive skew, posing a serious problem when trying to make inference. Furthermore, current approaches consider only one of the two processes at a time, neglecting any genomic signal that could arise from their simultaneous effects, preventing the possibility of jointly inferring parameters relating to both offspring distribution and population history. Here, we develop an extended Moran model with exponential population growth, and demonstrate that the underlying ancestral process converges to a time-inhomogeneous psi-coalescent. However, by applying a nonlinear change of time scale-analogous to the Kingman coalescent-we find that the ancestral process can be rescaled to its time-homogeneous analog, allowing the process to be simulated quickly and efficiently. Furthermore, we derive analytical expressions for the expected site-frequency spectrum under the time-inhomogeneous psi-coalescent, and develop an approximate-likelihood framework for the joint estimation of the coalescent and growth parameters. By means of extensive simulation, we demonstrate that both can be estimated accurately from whole-genome data. In addition, not accounting for demography can lead to serious biases in the inferred coalescent model, with broad implications for genomic studies ranging from ecology to conservation biology. Finally, we use our method to analyze sequence data from Japanese sardine populations, and find evidence of high variation in individual reproductive success, but few signs of a recent demographic expansion. Copyright © 2018 by the Genetics Society of America.

Stress during pregnancy alters the offspring hypothalamic, pituitary, adrenal, and testicular response to isolation on the day of weaning.

PubMed

Williams, M T; Davis, H N; McCrea, A E; Hennessy, M B

1999-01-01

Subjecting pregnant female rats to situations that activate the hypothalamic-pituitary-adrenal (HPA) axis can have long-term effects on the development of the offspring. Restraint under bright lights is a common method of stressing pregnant females that results in consistent behavioral changes in the offspring. We investigated the effects of gestationally administered restraint, bright lights, and heat on the HPA axis response of 21-day-old offspring following exposure to isolation in a novel environment or under resting conditions. Corticotropin-releasing factor titers in the hypothalamus were unaffected following isolation. Nonetheless, adrenocorticotropin hormone (ACTH) was found to be lower in the gestationally stressed offspring prior to or following the isolation period. Corticosterone was attenuated in gestationally stressed offspring following the postnatal stressor and there was also a tendency for the gestationally stressed females to have lower concentrations of aldosterone. Plasmatic testosterone levels were higher in the gestationally stressed males following the period of isolation. The present data suggest that the HPA axis of the offspring is differentially affected by the gestational stress procedure, that is, it is attenuated at the level of the pituitary and adrenal, but not at the level of the hypothalamus. These data have implications for behavioral differences observed in gestationally stressed animals.

Quantifying inbreeding avoidance through extra-pair reproduction

PubMed Central

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Germain, Ryan R; Duthie, A Bradley; Losdat, Sylvain; Wolak, Matthew E; Nietlisbach, Pirmin

2015-01-01

Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females’ alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females’ within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. PMID:25346331

Cortical thickness in symptomatic and asymptomatic bipolar offspring.

PubMed

Hanford, Lindsay C; Sassi, Roberto B; Minuzzi, Luciano; Hall, Geoffrey B

2016-05-30

Children of parents diagnosed with bipolar disorder are at greater risk for developing a variety of psychiatric disorders, however, the reasons remain unknown. The present study aimed to investigate gray matter integrity in high-risk bipolar offspring (HRO) and healthy offspring (HCO) using cortical thickness techniques. Here we examined healthy control offspring (HCO; n=20) and HRO with (n=17) or without (n=13) psychiatric symptoms. T1-weighted images were collected from all offspring, and cortical thickness and age-cortical thickness correlations were compared. HRO showed cortical thinning in superior and inferior temporal regions, supramarginal, and caudal and rostral middle frontal regions compared to HCO. When comparing HRO with and without psychiatric symptoms, we found cortical thinning in symptomatic offspring in the superior frontal and somatosensory related cortices. Age-thickness correlations showed a relatively consistent negative relationship in most regions in HCO, while the reverse was true for the HRO. These regions included parahippocampal, lateral orbitofrontal, and inferior temporal regions. Our study provides evidence of cortical thickness reductions among symptomatic and asymptomatic high-risk offspring during youth. Some of these alterations, found in regions of emotion processing and regulation, are evident only when associated with the presence of psychiatric symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring

PubMed Central

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

2016-01-01

Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE. PMID:27703194

Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring.

PubMed

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

2016-10-05

Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M 2 -, M 3 -muscarinic and P2X 1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE.

[Psychomotor development in offspring of mothers with post partum depression].

PubMed

Podestá L, Loreto; Alarcón, Ana María; Muñoz, Sergio; Legüe C, Marcela; Bustos, Luis; Barría P, Mauricio

2013-04-01

Postpartum depression (PPD) has adverse effects on psychomotor development of the offspring. To evaluate the relationship between PPD and psychomotor development in children aged 18 months, consulting in primary care. Cross-sectional study with 360 infants and their mothers. Children had their psychomotor evaluation at l8 months and mothers completed the Edinburgh Postnatal Depression Scale at 4 and 12 weeks postpartum. The prevalence of both PPD and psychomotor alteration was estimated. The association between PPD and psychomotor alteration, including confounding variables, was estimated through logistic multiple regression analysis. The prevalence of PPD and psychomotor alteration was 29 and 16%, respectively Mothers with PPD had twice the probability of having an offspring with psychomotor alteration (Odds ratio = 2.0, confidence intervals = 1.07-3.68). This probability was significantly higher among single mothers or those with an unstable partner. PPD has a detrimental impact on psychomotor development of children.

Gestational cortisol and social play shape development of marmosets' HPA functioning and behavioral responses to stressors.

PubMed

Mustoe, Aaryn C; Taylor, Jack H; Birnie, Andrew K; Huffman, Michelle C; French, Jeffrey A

2014-09-01

Both gestational cortisol exposure (GCE) and variability in postnatal environments can shape the later-life behavioral and endocrine outcomes of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the influence of GCE and social play on HPA functioning in developing marmosets. Maternal urinary cortisol samples were collected across pregnancy to determine GCE for 28 marmoset offspring (19 litters). We administered a social separation stressor to offspring at 6, 12, and 18 months of age, during which we collected urinary cortisol samples and behavioral observations. Increased GCE was associated with increased basal cortisol levels and cortisol reactivity, but the strength of this relationship decreased across age. Increased social play was associated with decreased basal cortisol levels and a marginally greater reduction in cortisol reactivity as offspring aged, regardless of offspring GCE. Thus, GCE is associated with HPA functioning, but socially enriching postnatal environments can alter the effects associated with increased fetal exposure to glucocorticoids. © 2014 Wiley Periodicals, Inc.

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.