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Introduction: Mammalian reproductive and somatic development is regulated by steroid hormones, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Based largely on information from humans, model organisms, and domesticated animals, testosterone (T) and the GH/IGF-1 system activate sexually differentiated development, promoting male-biased growth, often at a cost to health and survivorship. To test if augmented prenatal androgen exposure in females produces similar developmental patterns and trade-offs, we examine maternal effects in wild meerkats (Suricata suricatta), a non-model species in which adult females naturally, albeit differentially by status, express exceptionally high androgen concentrations, particularly during pregnancy. In this cooperative breeder, the early growth of daughters predicts future breeding status and reproductive success. Methods: We examine effects of normative and experimentally induced variation in maternal androgens on the ontogenetic patterns in offspring reproductive hormones (androstenedione, A4; T; estradiol, E2), IGF-1, growth from pup emergence at 1 month to puberty at 1 year, and survivorship. Specifically, we compare the male and female offspring of dominant control (DC or high-T), subordinate control (SC or lower-T), and dominant treated (DT or blocked-T) dams, the latter having experienced antiandrogen treatment in late gestation. Results: Meerkat offspring showed sex differences in absolute T and IGF-1 concentrations, developmental rates of A4 and E2 expression, and survivorship -- effects that were sometimes socially or environmentally modulated. Atypical for mammals were the early male bias in T that disappeared by puberty, the absence of sex differences in A4 and E2, and the female bias in IGF-1. Food availability was linked to steroid concentrations in females and to IGF-1, potentially growth, and survival in both sexes. Maternal treatment significantly affected rates of T, E2, and IGF-1 expression, and weight, with marginal effects on survivorship; offspring of DT dams showed peak IGF-1 concentrations and the best survivorship. Discussion: Maternal effects thus impact offspring development in meerkats, with associated trade-offs: Whereas prenatal androgens modify postnatal reproductive and somatic physiology, benefits associated with enhanced competitiveness in DC lineages may have initial costs of reduced IGF-1, delay in weight gain, and decreased survivorship. These novel data further confirm the different evolutionary and mechanistic pathways to cooperative breeding and call for greater consideration of natural endocrine variation in both sexes. [ABSTRACT FROM AUTHOR]

Risk factors associated with environmental exposure, especially during critical periods of intrauterine development, affect fetal development and increase the risk of certain diseases in adulthood including cardiovascular diseases (CVD). Hypoxia is considered the most common and clinically significant form of intrauterine stress that causes systemic pathological changes, in 78% of cases associated with cardiovascular system disorders. The purpose of this study was to evaluate the effects of acute hypoxia on the 10th day of gestation on heart rate and its regulation in rats' offspring of prepubescent and pubertal age, as well as to analyze the dependence of resulting disorders on gender. By the beginning of puberty the heart rate of rats survived prenatal hypoxia was significantly higher than in control accompanied by significant decrease in heart rate variability (dX) which naturally leads to stress index (SI) increase indicating growing sympathetic activity in heart rhythm regulation. At the same time the base heart rate in animals suffered intrauterine hypoxia turned out to be lower than in control. The fact that matured animals of both sexes, survived intrauterine hypoxia in early organogenesis, also show changes in dX and SI indicates long-term and irreversible disorders in heart rhythm regulation. Thus hypoxia during early organogenesis is of a programming nature potentially increasing the risk of developing CVD in adult animals. Moreover the autonomic system balance shift towards the activation of sympathetic tone was more pronounced in females making them more vulnerable to the risk of developing cardiac pathology in puberty. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that involves functional and structural defects in selective central nervous system (CNS) regions, harming the individual capability to process and respond to external stimuli, including impaired verbal and non-verbal communications. Etiological causes of ASD have not been fully clarified; however, prenatal activation of the innate immune system by external stimuli might infiltrate peripheral immune cells into the fetal CNS and activate cytokine secretion by microglia and astrocytes. For instance, genomic and postmortem histological analysis has identified proinflammatory gene signatures, microglia-related expressed genes, and neuroinflammatory markers in the brain during ASD diagnosis. Active neuroinflammation might also occur during the developmental stage, promoting the establishment of a defective brain connectome and increasing susceptibility to ASD after birth. While still under investigation, we tested the hypothesis whether the monocyte chemoattractant protein-1 (MCP-1) signaling is prenatally programmed to favor peripheral immune cell infiltration and activate microglia into the fetal CNS, setting susceptibility to autism-like behavior. In this review, we will comprehensively provide the current understanding of the prenatal activation of MCP-1 signaling by external stimuli during the developmental stage as a new selective node to promote neuroinflammation, brain structural alterations, and behavioral defects associated to ASD diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Low birth weight (BW) calves experience higher mortality, lower weights at calving, reduced milk yields in their first lactation, and longer intervals before first insemination. In human medicine, small for gestational age (SGA) babies are known to suffer from increased health risks. The aim of this study was to define SGA in Holstein Friesian (HF) calves, evaluate their body measurements, and identify prenatal risk factors for being born SGA. We used models to predict calf weight based on gestation length for male and female calves from nulli- and multiparous dams. Calves with a BW below the 10th percentile were classified as SGA. We then analyzed body measurements and identified associated risk factors. SGA calves had significantly smaller body measurements and different proportions compared to average and large calves. For nulliparous dams, a higher temperature–humidity index during the 2nd trimester and older age at birth increased the birth of SGA calves. For multiparous dams, both low and high milk production during pregnancy were linked to more SGA births. This study establishes SGA in HF calves and highlights the impact of prenatal factors on calf size at birth. Further research is needed to understand the long-term effects of being born SGA on growth, reproduction and productivity. Low birth weight (BW) calves exhibit higher mortality rates, reduced body weights at parturition, lower first-lactation milk yields, and longer parturition to first insemination intervals. In human medicine, small for gestational age (SGA) births are associated with increased perinatal morbidity and long-term metabolic risks. This study aimed to define SGA in Holstein Friesian (HF) calves, evaluate their body measurements and proportions, and identify its prenatal risk factors. Four linear regression models were built with weight as a function for gestation length for bull and heifer calves born from nulli- or multiparous dams. Calves with a BW below the 10th percentile were classified as SGA. Differences in body measurements were analyzed using ANOVA, and logistic regression models identified prenatal risk factors to be born SGA. Gestation length, calf sex, and dam parity were crucial variables in defining SGA. SGA calves had significantly smaller body measurements (p < 0.001) and larger body proportions (p < 0.001) compared to average and large calves. For nulliparous dams, a higher 2nd trimester temperature–humidity index (p = 0.032) and older age at parturition (>26 months, p = 0.026) significantly increased the birth of SGA calves. For multiparous dams, both low (<5800 kg, p = 0.049) and high (6700–8600 kg, p = 0.027) milk yields during gestation lead to more SGA births, although very high-yielding dams (>8600 kg) did not birth more SGA calves. This study establishes SGA in HF calves, suggests SGA calves are asymmetrical with evidence of "brain sparing", and highlights the impact of prenatal factors on calf size at birth. Further research is needed to determine the long-term effects of being born SGA on growth, reproductive performance, and productivity. [ABSTRACT FROM AUTHOR]

Environmental influences before and during pregnancy significantly impact offspring development. This study investigates open research questions regarding the associations between maternal early life stress (ELS), prenatal psychosocial stress, prenatal hair cortisol (HC), and birth outcomes in Argentinian women. Data on ELS, prenatal life events, HC (two samples representing first and second half of pregnancy), and birth outcomes were collected from middle‐class Argentinian women (N = 69) upon delivery. Linear mixed models indicated that HC increased from the first half to the second half of pregnancy with considerable variability in the starting values and slopes between individuals. Mothers who experienced more ELS, were taller, or more educated, tended to show lower increases in HC. Older age was positively related to HC increases. Our data did not suggest an interaction between ELS and prenatal life events in relation to HC. We found that the change in HC was most likely negatively associated with birth weight. Our data are most compatible with either a weak or the absence of an association between ELS or prenatal life events and absolute values of HC. Mothers with stronger increases in hair cortisol tended to have newborns with slightly lower birth weight. Hence, ELS and birthweight may either have been related to changes in cortisol exposure during pregnancy or to factors that influence accumulation or retention of cortisol in hair. [ABSTRACT FROM AUTHOR]

Both maternal metabolic dysregulation, e.g., gestational diabetes mellitus (GDM), and maternal supply of nutrients that participate in one-carbon (1C) metabolism, e.g., folate, choline, betaine, and vitamin B 12 , have been demonstrated to influence epigenetic modification such as DNA methylation, thereby exerting long-lasting impacts on growth and development of offspring. This study aimed to determine how maternal 1C nutrient intake was associated with DNA methylation and further, development of children, as well as whether maternal GDM status modified the association in a prospective cohort. In this study, women with (n = 18) and without (n = 20) GDM were recruited at 25–33 weeks gestation. Detailed dietary intake data was collected by 3-day 24-h dietary recall and nutrient levels in maternal blood were also assessed at enrollment. The maternal-child dyads were invited to participate in a 2-year follow-up during which anthropometric measurement and the Bayley Scales of Infant and Toddler Development™ Screening Test (Third Edition) were conducted on children. The association between maternal 1C nutrients and children's developmental outcomes was analyzed with a generalized linear model controlling for maternal GDM status. We found that children born to mothers with GDM had lower scores in the language domain of the Bayley test (p = 0.049). Higher maternal food folate and choline intakes were associated with better language scores in children (p = 0.01 and 0.025, respectively). Higher maternal food folate intakes were also associated with better cognitive scores in children (p = 0.002). Higher 1C nutrient intakes during pregnancy were associated with lower body weight of children at 2 years of age (p < 0.05). However, global DNA methylation of children's buccal cells was not associated with any maternal 1C nutrients. In conclusion, higher 1C nutrient intake during pregnancy was associated with lower body weight and better neurodevelopmental outcomes of children. This may help overcome the lower language scores seen in GDM-affected children in this cohort. Studies in larger cohorts and with a longer follow-up duration are needed to further delineate the relationship between prenatal 1C nutrient exposure, especially in GDM-affected pregnancies, and offspring health outcomes. [ABSTRACT FROM AUTHOR]

IntroductionMammalian reproductive and somatic development is regulated by steroid hormones, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Based largely on information from humans, model organisms, and domesticated animals, testosterone (T) and the GH/IGF-1 system activate sexually differentiated development, promoting male-biased growth, often at a cost to health and survivorship. To test if augmented prenatal androgen exposure in females produces similar developmental patterns and trade-offs, we examine maternal effects in wild meerkats (Suricata suricatta), a non-model species in which adult females naturally, albeit differentially by status, express exceptionally high androgen concentrations, particularly during pregnancy. In this cooperative breeder, the early growth of daughters predicts future breeding status and reproductive success.MethodsWe examine effects of normative and experimentally induced variation in maternal androgens on the ontogenetic patterns in offspring reproductive hormones (androstenedione, A4; T; estradiol, E2), IGF-1, growth from pup emergence at 1 month to puberty at 1 year, and survivorship. Specifically, we compare the male and female offspring of dominant control (DC or high-T), subordinate control (SC or lower-T), and dominant treated (DT or blocked-T) dams, the latter having experienced antiandrogen treatment in late gestation.ResultsMeerkat offspring showed sex differences in absolute T and IGF-1 concentrations, developmental rates of A4 and E2 expression, and survivorship — effects that were sometimes socially or environmentally modulated. Atypical for mammals were the early male bias in T that disappeared by puberty, the absence of sex differences in A4 and E2, and the female bias in IGF-1. Food availability was linked to steroid concentrations in females and to IGF-1, potentially growth, and survival in both sexes. Maternal treatment significantly affected rates of T, E2, and IGF-1 expression, and weight, with marginal effects on survivorship; offspring of DT dams showed peak IGF-1 concentrations and the best survivorship.DiscussionMaternal effects thus impact offspring development in meerkats, with associated trade-offs: Whereas prenatal androgens modify postnatal reproductive and somatic physiology, benefits associated with enhanced competitiveness in DC lineages may have initial costs of reduced IGF-1, delay in weight gain, and decreased survivorship. These novel data further confirm the different evolutionary and mechanistic pathways to cooperative breeding and call for greater consideration of natural endocrine variation in both sexes.

Maternal adversity and prenatal stress confer risk for child behavioral health problems. Few studies have examined this intergenerational process across multiple dimensions of stress; fewer have explored potential protective factors. Using a large, diverse sample of mother-child dyads, we examined associations between maternal childhood trauma, prenatal stressors, and offspring socioemotional-behavioral development, while also examining potential resilience-promoting factors. The Conditions Affecting Neurocognitive Development and Learning and Early Childhood (CANDLE) study prospectively followed 1503 mother-child dyads (65% Black, 32% White) from pregnancy. Exposures included maternal childhood trauma, socioeconomic risk, intimate partner violence, and geocode-linked neighborhood violent crime during pregnancy. Child socioemotional-behavioral functioning was measured via the Brief Infant Toddler Social Emotional Assessment (mean age = 1.1 years). Maternal social support and parenting knowledge during pregnancy were tested as potential moderators. Multiple linear regressions (N = 1127) revealed that maternal childhood trauma, socioeconomic risk, and intimate partner violence were independently, positively associated with child socioemotional-behavioral problems at age one in fully adjusted models. Maternal parenting knowledge moderated associations between both maternal childhood trauma and prenatal socioeconomic risk on child problems: greater knowledge was protective against the effects of socioeconomic risk and was promotive in the context of low maternal history of childhood trauma. Findings indicate that multiple dimensions of maternal stress and adversity are independently associated with child socioemotional-behavioral problems. Further, modifiable environmental factors, including knowledge regarding child development, can mitigate these risks. Both findings support the importance of parental screening and early intervention to promote child socioemotional-behavioral health.

Accumulating evidence suggests that maternal exposure to objectively stressful events and subjective distress during pregnancy may have intergenerational impacts on children's mental health, yet evidence is limited. In a multisite longitudinal cohort (N = 454), we used multi-variable linear regression models to evaluate the predictive value of exposure to stressful events and perceived distress in pregnancy for children's internalizing problems, externalizing problems, and adaptive skills at age 4. We also explored two- and three-way interactions between stressful events, distress, and child sex. Both objective and subjective maternal stress independently predicted children's behavior, with more stressful events and higher distress predicting more internalizing and externalizing problems and worse adaptability; stress types did not significantly interact. There was some evidence that more stressful events predicted higher externalizing behaviors only for girls. Three-way interactions were not significant. The current findings highlight the importance of considering the type of stress measurement being used (e.g., counts of objective event exposure or subjective perceptions), suggest prenatal stress effects may be transdiagnostic, and meet calls for rigor and reproducibility by confirming these independent main effects in a relatively large group of families across multiple U.S. regions. Results point to adversity prevention having a two-generation impact and that pre- and postnatal family-focused intervention targets may help curb the rising rates of children's mental health problems.

ObjectiveChildhood trauma exacts a lasting toll on one's own mental health and the health of one's offspring; however, limited research has examined the pathways through which this intergenerational transmission occurs. This study aimed to identify the transactions and mechanisms that link maternal early life trauma, maternal depressive symptoms, and children's internalizing symptoms.MethodA pregnancy cohort of N = 1462 mothers (66% Black, 32% White, 2% Other race) reported their childhood trauma exposure and depressive symptoms during pregnancy. Maternal depressive and children's internalizing symptoms were measured repeatedly when offspring were 12, 24, 36, and 48-60 months of age. A path model tested the transactional associations between maternal and child symptomatology and mediation of maternal childhood trauma on offspring symptoms via maternal depressive symptoms.ResultsMothers' childhood trauma history was related to greater prenatal and postnatal (12 and 24 months) maternal depressive symptoms, which were prospectively associated with offspring internalizing problems at 36 and 48-60 months. Child-directed effects on maternal depressive symptoms were not observed. The association of maternal trauma on children's internalizing at 36 months was mediated by maternal depressive symptoms at 24 months.LimitationsAssessments of the key study variables were provided by mothers. Childhood trauma was evaluated retrospectively.ConclusionWomen's experiences of adversity in childhood have persistent and cumulative effects on their depression during the transition to parenthood, which is associated with risk for children's internalizing. Given the two-generation influence of maternal childhood trauma exposure, attending to its impact may protect both caregivers and their children.

ObjectiveMaternal health and wellness during pregnancy are associated with long-term health outcomes in children. The current study examined whether infants of women who participated in a mindfulness-based intervention during pregnancy that reduced levels of stress and depression, increased physical activity, and improved glucose tolerance differed on biobehavioral markers of psychopathological and physical health risk compared with infants of women who did not.MethodsParticipants were 135 mother-infant dyads drawn from a racially and ethnically diverse, low-income sample experiencing high stress. The women participated in an intervention trial during pregnancy that involved assignment to either mindfulness-based intervention or treatment-as-usual (TAU). Infants of women from both groups were assessed at 6 months of age on sympathetic (preejection period), parasympathetic (respiratory sinus arrhythmia), and observed behavioral (negativity and object engagement) reactivity and regulation during the still face paradigm. Linear mixed-effects and generalized linear mixed-effects models were used to examine treatment group differences in infant outcomes.ResultsRelative to those in the intervention group, infants in the TAU group showed a delay in sympathetic activation and subsequent recovery across the still face paradigm. In addition, infants in the intervention group engaged in higher proportions of self-regulatory behavior during the paradigm, compared with the TAU group. No significant effect of intervention was found for parasympathetic response or for behavioral negativity during the still face paradigm.ConclusionsFindings provide evidence that maternal participation in a short-term, group mindfulness-based intervention during pregnancy is associated with the early development of salutary profiles of biobehavioral reactivity and regulation in their infants. Because these systems are relevant for psychopathology and physical health, prenatal behavioral interventions may benefit two generations.

Abstract Background Gestational sleep apnea is a hypoxic sleep disorder that affects 8–26% of pregnancies and increases the risk for central nervous system dysfunction in offspring. Specifically, there are sex differences in the sensitivity of the fetal hippocampus to hypoxic insults, and hippocampal impairments are associated with social dysfunction, repetitive behaviors, anxiety, and cognitive impairment. Yet, it is unclear whether gestational sleep apnea impacts these hippocampal-associated functions and if sex and age modify these effects. To examine the relationship between gestational sleep apnea and hippocampal-associated behaviors, we used chronic intermittent hypoxia (CIH) to model late gestational sleep apnea in pregnant rats. We hypothesized that late gestational CIH would produce sex- and age-specific social, anxiety-like, repetitive, and cognitive impairments in offspring. Methods Timed pregnant Long-Evans rats were exposed to CIH or room air normoxia from GD 15–19. Behavioral testing of offspring occurred during either puberty or young adulthood. To examine gestational hypoxia-induced behavioral phenotypes, we quantified hippocampal-associated behaviors (social function, repetitive behaviors, anxiety-like behaviors, and spatial memory and learning), hippocampal neuronal activity (glutamatergic NMDA receptors, dopamine transporter, monoamine oxidase-A, early growth response protein 1, and doublecortin), and circulating hormones in offspring. Results Late gestational CIH induced sex- and age-specific differences in social, repetitive, and memory functions in offspring. In female pubertal offspring, CIH impaired social function, increased repetitive behaviors, and elevated circulating corticosterone levels but did not impact memory. In contrast, CIH transiently induced spatial memory dysfunction in pubertal male offspring but did not impact social or repetitive functions. Long-term effects of gestational CIH on social behaviors were only observed in female offspring, wherein CIH induced social disengagement and suppression of circulating corticosterone levels in young adulthood. No effects of gestational CIH were observed in anxiety-like behaviors, hippocampal neuronal activity, or circulating testosterone and estradiol levels, regardless of sex or age of offspring. Conclusions Our results indicate that hypoxia-associated pregnancy complications during late gestation can increase the risk for behavioral and physiological outcomes in offspring, such as social dysfunction, repetitive behaviors, and cognitive impairment, that are dependent on sex and age.

The objective of this research was to determine the effects of mid-gestational maternal inflammation on performance, carcass characteristics, and meat quality of offspring. Pregnant gilts were administered either lipopolysaccharide (LPS ; n  = 7) or saline (CON , n  = 7) from days 70 to 84 of gestation. Gilts assigned to the LPS treatment were administered an intravenous injection of reconstituted LPS every other day with a beginning dose of 10 μg LPS/kg body weight and subsequent doses increasing by 12%, while CON gilts received intravenous injections of comparable volumes of saline. Gilts farrowed naturally, and at day 66 of age, a total of 59 pigs, both barrows and gilts began a 3-phase feeding regimen designed to meet or exceed nutrient requirements for growing-finishing pigs. Pigs were weighed on days 0, 35, 70, and 105 of the finishing trial to determine average daily gain, average daily feed intake, and gain-to-feed ratio (G:F). On day 106, pigs were slaughtered under the supervision of the U.S. Department of Agriculture Food Safety Inspection Service. Ending live weight, hot carcass weight, and dressing percentage were determined. The left side of carcasses was weighed and fabricated to determine carcass cutting yields. The semitendinosus was collected for histological samples. Fresh belly characteristics and loin quality were measured. Two chops were collected for Warner–Bratzler shear force and proximate analysis. No differences (P  ≥ 0.13) between LPS and CON pigs were observed for growth performance in phases 1, 2, 3, or overall (days 0 to 105) performance with the exception of overall G:F reduced in CON pigs compared with LPS pigs (P  = 0.03). There was a tendency for carcass yield to be reduced (P  = 0.06; 0.82% units) in LPS pigs compared with CON pigs. Additionally, longissimus muscle area tended to be reduced (P  = 0.10) 2.27 cm2 in LPS compared with CON pigs. Loin chop quality traits including instrumental color, subjective color, marbling, firmness, pH, and drip loss were not different (P  ≥ 0.09) between LPS and CON pigs. Fresh belly characteristics were not different (P  ≥ 0.22) between LPS and CON pigs. There were no differences in primal and subprimal weights, except that LPS pigs tended to have a reduction (P  ≥ 0.07) in tenderloin and Canadian back weights compared with CON pigs. Furthermore, LPS pigs had no differences (P  ≥ 0.25) in muscle fiber composition or size; however, LPS pigs tended (P  = 0.10) to have a 13% reduction in estimated muscle fibers number compared with CON pigs. In summary, mid-gestational inflammation did not result in reduced meat quality, growth performance, or carcass yields of offspring. [ABSTRACT FROM AUTHOR]

The objective was to determine the effects of maternal inflammation on offspring muscle development and postnatal innate immune response. Sixteen first-parity gilts were randomly allotted to repeated intravenous injections with lipopolysaccharide (LPS; n  = 8, treatment code INFLAM) or comparable volume of phosphate buffered saline (CON, n  = 8). Injections took place every other day from gestational day (GD) 70 to GD 84 with an initial dose of 10 μg LPS/kg body weight (BW) increasing by 12% each time to prevent endotoxin tolerance. On GD 70, 76, and 84, blood was collected at 0 and 4 h postinjection via jugular or ear venipuncture to determine tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β concentrations. After farrowing, litter mortality was recorded, and the pig closest to litter BW average was used for dissection and muscle fiber characterization. On weaning (postnatal day [PND] 21), pigs were weighed individually and 2 barrows closest to litter BW average were selected for another study. The third barrow closest to litter BW average was selected for the postnatal LPS challenge. On PND 52, pigs were given 5 μg LPS/kg BW via intraperitoneal injection, and blood was collected at 0, 4, and 8 h postinjection to determine TNF-α concentration. INFLAM gilt TNF-α concentration increased (P  < 0.01) 4 h postinjection compared to 0 h postinjection, while CON gilt TNF-α concentration did not differ between time points. INFLAM gilt IL-6 and IL-1β concentrations increased (P  = 0.03) 4 h postinjection compared to 0 h postinjection on GD 70, but did not differ between time points on GD 76 and 84. There were no differences between INFLAM and CON gilts litter mortality outcomes (P ≥ 0.13), but INFLAM pigs were smaller (P = 0.04) at birth and tended (P = 0.09) to be smaller at weaning. Muscle and organ weights did not differ (P ≥ 0.17) between treatments, with the exception of semitendinosus, which was smaller (P < 0.01) in INFLAM pigs. INFLAM pigs tended (P = 0.06) to have larger type I fibers. INFLAM pig TNF-α concentration did not differ across time, while CON pig TNF-α concentration peaked (P = 0.01) 4 h postinjection. TNF-α concentration did not differ between treatments at 0 and 8 h postinjection, but CON pigs had increased (P = 0.01) TNF-α compared to INFLAM pigs 4 h postinjection. Overall, maternal immune activation did not alter pig muscle development, but resulted in suppressed innate immune activation. [ABSTRACT FROM AUTHOR]

Summary: Background: Leptin resistance occurs with obesity, but it is unknown if individuals at risk for obesity develop leptin resistance prior to obesity. Objective: Investigate whether leptin resistance is independent of weight status in children at risk for obesity due to intrauterine exposure to maternal obesity or gestational diabetes mellitus (GDM). Methods: Mother–child dyads (N = 179) were grouped by maternal pregnancy weight and GDM status: (1) normal weight, no GDM; (2) overweight/obesity, no GDM; (3) overweight/obesity with GDM. Children (4–10 years) were further stratified by current body mass index (BMI) <85th or ≥85th percentile. Leptin resistance of children and mothers was calculated as fasting leptin/fat mass index. Two‐way ANOVA was used to assess whether leptin concentrations and leptin resistance differed by current weight status or in utero exposure group, after adjusting for race, sex and Tanner stage. Results: Children with a BMI ≥85th percentile had more leptin resistance than those with a BMI <85th percentile (p < 0.001), but leptin resistance did not differ by in utero exposure. Similarly, leptin resistance in women was associated with weight status and not prior GDM. Conclusions: Results suggest that leptin concentrations are associated with obesity but not risk for obesity based on in utero exposure to maternal obesity or GDM. [ABSTRACT FROM AUTHOR]

The present study characterizes the relations among maternal condition, litter size, birth condition, and growth in body weight for a population of common marmosets. The subjects of the study were marmosets born into a single colony between 1994 and 2001. Three sets of analyses were conducted to answer the following questions: 1) Is there a relationship between litter size, maternal condition, and birth condition? In the study population, maternal body weight, maternal age, litter size, and birth condition were related in a complex fashion. Birth weight and prenatal long-bone growth, as reflected in knee–heel length, were both related to maternal age, with older mothers supporting higher prenatal growth. Age and maternal condition appeared to interact as determinants of long-bone growth, as the combination of older and larger mothers resulted in significantly longer knee–heel lengths in their offspring. 2) Is there a relationship between birth condition or maternal condition and subsequent growth or final adult size? The early growth rate in this population was similar to early growth rates reported for three different marmoset colonies, suggesting that early growth may be relatively inflexible in this species. However, within this population, the variation that did occur in early growth rate was related to birth weight and maternal weight. Later growth and adult weight were related to birth weight and litter size: small twin infants displayed slower later growth rates and were smaller as adults than twins that began life at a higher birth weight, while the birth weight of triplets was not related to adult size. In these marmosets, small infants that were the result of increased litter size differed from small infants whose small birth size resulted from other factors. This reinforces the proposal that the causes of low birth weight will be relevant to the development of the marmoset as a model of prenatal environmental effects. Am. J. Primatol. 62:83–94, 2004. © 2004 Wiley-Liss, Inc.

ObjectivesTo examine the association between prenatal stress and infant physical health in the first year of life within an understudied, racially and ethnically diverse, highly stressed community sample. We expected that greater stress exposure would predict higher rates of infant illness.Study designLow-income, racially/ethnically diverse, overweight women with low medical risk pregnancies were recruited (2011-2014) during pregnancy. Pregnancy Stressful Life Events were assessed retrospectively (mean, 11.88 months postpartum). Perceived stress was assessed twice during pregnancy (at a mean of 17.4 weeks and again at a mean of 25.6 weeks) and at 6 months postpartum. Women with live births (n = 202) were invited; 162 consented to the offspring study. Medical records from pediatric clinics and emergency departments for 148 infants were abstracted for counts of total infectious illnesses, total noninfectious illness, and diversity of illnesses over the first year of life.ResultsThe final analytic sample included 109 women (mean age, 28.08 years) and their infants. In covariate-adjusted negative binomial models, maternal perceptions of stress across pregnancy were positively associated with infant illness. Each 1-point increase in average stress was associated with a 38% increase in incidence of infant infections (Incidence rate ratio, 1.38; 95% CI, 1.01-1.88; P

Background: Gestational sleep apnea is a hypoxic sleep disorder that affects 8–26% of pregnancies and increases the risk for central nervous system dysfunction in offspring. Specifically, there are sex differences in the sensitivity of the fetal hippocampus to hypoxic insults, and hippocampal impairments are associated with social dysfunction, repetitive behaviors, anxiety, and cognitive impairment. Yet, it is unclear whether gestational sleep apnea impacts these hippocampal-associated functions and if sex and age modify these effects. To examine the relationship between gestational sleep apnea and hippocampal-associated behaviors, we used chronic intermittent hypoxia (CIH) to model late gestational sleep apnea in pregnant rats. We hypothesized that late gestational CIH would produce sex- and age-specific social, anxiety-like, repetitive, and cognitive impairments in offspring. Methods: Timed pregnant Long-Evans rats were exposed to CIH or room air normoxia from GD 15–19. Behavioral testing of offspring occurred during either puberty or young adulthood. To examine gestational hypoxia-induced behavioral phenotypes, we quantified hippocampal-associated behaviors (social function, repetitive behaviors, anxiety-like behaviors, and spatial memory and learning), hippocampal neuronal activity (glutamatergic NMDA receptors, dopamine transporter, monoamine oxidase-A, early growth response protein 1, and doublecortin), and circulating hormones in offspring. Results: Late gestational CIH induced sex- and age-specific differences in social, repetitive, and memory functions in offspring. In female pubertal offspring, CIH impaired social function, increased repetitive behaviors, and elevated circulating corticosterone levels but did not impact memory. In contrast, CIH transiently induced spatial memory dysfunction in pubertal male offspring but did not impact social or repetitive functions. Long-term effects of gestational CIH on social behaviors were only observed in female offspring, wherein CIH induced social disengagement and suppression of circulating corticosterone levels in young adulthood. No effects of gestational CIH were observed in anxiety-like behaviors, hippocampal neuronal activity, or circulating testosterone and estradiol levels, regardless of sex or age of offspring. Conclusions: Our results indicate that hypoxia-associated pregnancy complications during late gestation can increase the risk for behavioral and physiological outcomes in offspring, such as social dysfunction, repetitive behaviors, and cognitive impairment, that are dependent on sex and age. Plain Language Summary: Sleep apnea during late pregnancy is a common pregnancy complication that can impact the brain development of children born to mothers with sleep apnea. Children with impaired brain development may present with decreased social skills, memory issues, anxiety, and compulsivity. It is unclear if there is a cause and effect relationship between sleep apnea during late pregnancy and behavioral changes in offspring. Additionally, it is unknown whether male or female sex or age of the offspring affects these relationships. In this study, we exposed pregnant rats to a model of sleep apnea called chronic intermittent hypoxia (CIH) within late gestation and examined the behavior of the offspring and brain activity during puberty and young adulthood. We found that CIH during late pregnancy had long-term effects in the offspring that were different in males and females. Notably, female offspring displayed social impairments in response to late gestation CIH, whereas male offspring displayed cognitive dysfunction. Highlights: This is the first study to examine the effects of late gestational CIH on social, anxiety, and cognitive function in rat offspring. Short term hypoxia during late gestation induced sex- and age-specific differences in offspring social and cognitive function. Late gestational hypoxia induced sustained social impairments and corticosterone dysregulation in female offspring that were present during puberty and young adulthood. [ABSTRACT FROM AUTHOR]

Introduction: Prenatal programming with dexamethasone increases the risk of the development of hyperglycaemia and insulin resistance, leading to diabetes in adulthood. Dexamethasone also causes a decline in renal glomerular filtration in the adult offspring. Sodium‐glucose cotransporter‐2 (SGLT2) plays a significant role in regulating blood glucose and renal haemodynamics in diabetic patients. However, the role of SGLT2 in dexamethasone‐induced programming and the putative sex‐dependent effects on the changes named earlier is unknown. Therefore, this study aimed to investigate the impact of maternal dexamethasone treatment on glucose tolerance, insulin sensitivity, renal perfusion and renal function in adult male and female offspring and the possible contribution of SGLT2 to these changes. Methods and Results: Pregnant Sprague Dawley rats (F0) were treated with either vehicle or dexamethasone (0.2 mg/kg ip) from gestation Day 15 to 20. F1 males and F1 females were randomly selected from each mother at 4 months of age. There was no change in serum Na+, Na+ excretion rate, glucose tolerance or insulin sensitivity in F1 male or female rats. However, dexamethasone caused significant glomerular hypertrophy and decreases in CSinistrin and CPAH indicating decreased glomerular filtration rate and renal plasma flow, respectively, in dexamethasone‐treated F1 male but not female rats. Dexamethasone did not affect SGLT2 mRNA or protein expression in F1 males or females. Conclusion: We conclude that dexamethasone‐mediated prenatal programming of glomerular volume, renal function and haemodynamics is sex‐dependent, occurring only in adult male offspring. [ABSTRACT FROM AUTHOR]

Prenatal androgen exposure modulates the development of the brain, with lasting effects on its function and behavior over the infant's life span. Environmental factors during pregnancy, in particular maternal stress, have been shown to influence the androgen load of the unborn child. We here addressed the research gap on whether a mindfulness intervention or a pregnancy education administered to pregnant women more affects the androgen exposure of the unborn child (quantified by the proxies of second-to-fourth digit length ratio (2D:4D) and anogenital distance assessed one year after delivery and at delivery, respectively). Moreover, we tested the mindfulness intervention's effects on maternal perceived stress, anxiety, depressiveness, and mindfulness. Pregnant women (gestation weeks 8–14) were randomized to a 15-week app-based mindfulness-oriented intervention (N = 72) or a pregnancy education intervention (control condition; N = 74). The mindfulness-oriented group did not significantly differ from the pregnancy education group in infants' 2D:4D or anogenital distance (partial η2 ≤ 0.01) or in maternal stress, anxiety, depressiveness, or mindfulness. However, the descriptive results indicate that across pregnancy, stress and anxiety decreased and mindfulness increased in both groups. Overall, this study did not show that the mindfulness intervention (relative to the pregnancy education) reduced the prenatal androgen exposure of the unborn children or improved the maternal outcomes significantly. [ABSTRACT FROM AUTHOR]

Evidence suggests that adversity experienced during fetal development may shape infant physiologic functioning and temperament. Parental sensitivity is associated with child stress regulation and may act as a buffer against risk for intergenerational health effects of pre- or postnatal adversity. Building upon prior evidence in a racially and ethnically diverse sample of infants (M infant age = 6.5 months) and women of low socioeconomic status, this study examined whether coded parenting sensitivity moderated the association between an objective measure of prenatal stress exposures (Stressful Life Events (SLE)) and infant parasympathetic (respiratory sinus arrhythmia; RSA) or sympathetic (pre-ejection period; PEP) nervous system functioning assessed during administration of the Still-Face-Paradigm (SFP) (n = 66), as well as maternal report of temperament (n = 154). Results showed that parental sensitivity moderated the associations between prenatal stress exposures and infant RSA reactivity, RSA recovery, PEP recovery, and temperamental negativity. Findings indicate that greater parental sensitivity is associated with lower infant autonomic nervous system reactivity and greater recovery from challenge. Results support the hypothesis that parental sensitivity buffers infants from the risk of prenatal stress exposure associations with offspring cross-system physiologic reactivity and regulation, potentially shaping trajectories of health and development and promoting resilience. [ABSTRACT FROM AUTHOR]

Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli. Accordingly, pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu. Maternal exposure to high-energy dense diets can affect motivated behavior in the offspring leading to addiction and impaired sociability. A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring. While still under investigation, prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring. The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring. We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth. We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.

Abstract Introduction Prenatal programming with dexamethasone increases the risk of the development of hyperglycaemia and insulin resistance, leading to diabetes in adulthood. Dexamethasone also causes a decline in renal glomerular filtration in the adult offspring. Sodium‐glucose cotransporter‐2 (SGLT2) plays a significant role in regulating blood glucose and renal haemodynamics in diabetic patients. However, the role of SGLT2 in dexamethasone‐induced programming and the putative sex‐dependent effects on the changes named earlier is unknown. Therefore, this study aimed to investigate the impact of maternal dexamethasone treatment on glucose tolerance, insulin sensitivity, renal perfusion and renal function in adult male and female offspring and the possible contribution of SGLT2 to these changes. Methods and Results Pregnant Sprague Dawley rats (F0) were treated with either vehicle or dexamethasone (0.2 mg/kg ip) from gestation Day 15 to 20. F1 males and F1 females were randomly selected from each mother at 4 months of age. There was no change in serum Na+, Na+ excretion rate, glucose tolerance or insulin sensitivity in F1 male or female rats. However, dexamethasone caused significant glomerular hypertrophy and decreases in CSinistrin and CPAH indicating decreased glomerular filtration rate and renal plasma flow, respectively, in dexamethasone‐treated F1 male but not female rats. Dexamethasone did not affect SGLT2 mRNA or protein expression in F1 males or females. Conclusion We conclude that dexamethasone‐mediated prenatal programming of glomerular volume, renal function and haemodynamics is sex‐dependent, occurring only in adult male offspring.

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Highlights Brain maturation of the nigrostriatal pathway is sex- and age- dependent. Exposure to hypoxia in late pregnancy impacts brain maturation of the nigrostriatal pathway that can be observed during puberty and young adulthood. Gestational hypoxia impacted female offspring during puberty more than males, whereas it impacted male offspring during young adulthood more than females. These novel findings demonstrate that hypoxic insults during pregnancy mediate developmental programming of the cortical and subcortical pathways, in which male offspring exhibit long-term adverse effects compared to female offspring. Long-term adverse effects of gestational hypoxia in offspring can occur in the absence of pregnancy complications, especially if they occur within critical embryological developmental periods.

The objective was to evaluate the influence of melatonin supplementation in pregnant beef cattle grazing toxic, endophyte-infected tall fescue (E+) on post-calving dam body weight (BW), milk production, and preweaning growth of steer calves. Multiparous cows were artificially inseminated with sex-sorted semen (Y chromosome-bearing sperm) from a single Red Angus sire and maintained on pastures free from E+ fescue prior to the start of the treatment period. Pregnant cows were assigned to one of three treatment groups with two replications per treatment: non-toxic, novel endophyte-infected (NE+) tall fescue without melatonin supplementation (NE+/NM; n = 15), E+ fescue with melatonin supplementation (E+/M; n = 16), and E+ fescue without melatonin supplementation (E+/NM; n = 18). The treatment period was over 70 d between May and July (d 147 ± 1 to 217 ± 1 of gestation). A commercially available feed was mixed with melatonin (100 µg/kg BW) or without melatonin and hand-fed to each cow daily. At the conclusion of the treatment period (56 ± 18 d before parturition), cattle were moved to a single group and maintained on pastures free from E+ fescue for the remainder of the study. Dams and steer calves were weighed at d 0, 28, 56, 84, 112, 140, and 168 relative to calving (d 0 = calving). Four-hour milk yields on d 28 ± 3 and d 56 ± 3 were used to estimate daily milk volume and weight. Dam and calf BW were analyzed using the MIXED procedure of SAS specific for repeated measures with treatment, time, and the interaction as fixed effects and replicate as random. Calf birth weight, dam milk volume, and dam milk weight were analyzed using the MIXED procedure of SAS with treatment as a fixed effect and replicate as random. On d 28, estimated daily milk volume and weight were decreased (P < 0.05) in E+/NM dams relative to NE+/NM dams. On d 56, estimated daily milk volume and weight were decreased (P < 0.03) in E+/NM and E+/M dams relative to NE+/ NM dams. There was an effect of time for dam and calf weights (P < 0.01). There was a treatment by time interaction for calf body weight, with calves born to E+/NM dams having decreased body weight relative to calves born to NE+/NM and E+/M dams from d 112 to d 168 (P = 0.02). There were no other effects of treatment, time, or the interaction (P > 0.05). These data suggest melatonin supplemented to pregnant crossbred multiparous beef cows grazing endophyteinfected tall fescue during mid-late gestation may increase preweaning growth of steer calves. [ABSTRACT FROM AUTHOR]

The idea that risk for psychiatric disorders may be transmitted intergenerationally via prenatal programming places interest in the prenatal period as a critical moment during which intervention efforts may have a strong impact, yet studies testing whether prenatal interventions also protect offspring are limited. The present umbrella review of systematic reviews and meta-analyses (SRMAs) of randomized controlled trials aimed to synthesize the available evidence and highlight promising avenues for intervention. Overall, the literature provides mixed and limited evidence in support of prenatal interventions. Thirty SRMAs were included. Of the 23 SRMAs that reported on prenatal depression interventions, 16 found a significant effect (average standard mean difference = −0.45, SD = 0.25). Similarly, 13 of the 20 SRMAs that reported on anxiety outcomes documented significant reductions (average standard mean difference = −0.76, SD = 0.95 or −0.53/0.53 excluding one outlier). Only 4 SRMAs reported child outcomes, and only 2 (of 10) analyses showed significant effects of prenatal interventions (massage and telephone support on neonatal resuscitation [relative risk = 0.43] and neonatal intensive care unit admissions [relative risk = 0.91]). Notably missing, perhaps due to our strict inclusion criteria (inclusion of randomized controlled trials only), were interventions focusing on key facets of prenatal health (e.g., whole diet, sleep). Structural interventions (housing, access to health care, economic security) were not included, although initial success has been documented in non-SRMAs. Most notably, none of the SRMAs focused on offspring mental health or neurodevelopmental outcomes. Given the possibility that interventions deployed in this period will positively impact the next generation, randomized trials that focus on offspring outcomes are urgently needed. [ABSTRACT FROM AUTHOR]

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother–infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament. [ABSTRACT FROM AUTHOR]

Isoflavones represent a class of phytoestrogens present in plants. In dairy cows, dietary isoflavones have been shown to negatively affect reproductive performance. To the best of our knowledge, no studies have yet been conducted to determine if calves are pre- or neonatally confronted with isoflavones and their metabolites. In the present study, we hypothesize that isoflavones are passed on from the dam to the offspring in utero. Twenty-three pregnant Holstein Friesian dams and their calves, originating from three commercial dairy farms in Belgium, were included. Heparin blood samples were collected during the first, second, and third trimester of gestation from all pregnant dams. Heparin blood and hair samples were obtained from the offspring within 24 h after parturition. Colostrum samples were collected from a subset of eight dams to determine the concentration of isoflavones and their metabolites. During the first and second trimester of gestation, the dams were fed either a youngstock (nulliparous dams) or a lactation (multiparous dams) diet. During the third trimester, both groups received a similar dry cow diet. Genistein and daidzein levels were unaffected by diet type, while their metabolite [equol, dihydrodaidzein (DHD), and o-desmethylangolensin (ODMA)] concentrations were significantly higher in the lactation group. Furthermore, metabolite concentrations decreased significantly during gestation. Isoflavones and their metabolites were detected in all colostrum samples. No correlation could be found between levels in colostrum and blood of pregnant dams or calves. Peripheral levels of isoflavones and their metabolites were significantly lower in newborn calves in comparison to their dams. Genistein and daidzein concentrations were found to be significantly higher in the calves' hair versus blood samples, suggesting prenatal exposure to isoflavones for an extended period of time. In contrast, no isoflavone metabolites were detected in the calves' hair samples. This is the first study to demonstrate that dairy calves are exposed to isoflavones during the developmentally most sensitive period of their lives. Results obtained pave the way for more extensive research to examine which effects isoflavones might have on developing organ systems like the reproductive system. • Isoflavones are plant based phytoestrogens. • Isoflavones and their metabolites circulate at varying levels in the blood of cattle during gestation. • Isoflavones are detectable in the colostrum of cows. • Isoflavones are detectable in the blood and hair of the cows' offspring shortly after calving. • Isoflavone metabolites are not detectable in the calves' hair. [ABSTRACT FROM AUTHOR]

Maternal body mass index (BMI) influences pregnancy and birth outcomes along with child metabolic and neurodevelopmental health and fetal sex may be a moderating factor in these effects. Alternations in autonomic nervous system (ANS) functioning, identified in heart rate (HR) measurements, could present early markers of these prenatal programming effects in both the mother and the developing fetus. This study examines the associations between pre-pregnancy BMI and maternal and fetal ANS functioning and infant postnatal behavioral outcomes stratified by fetal sex. Pregnant women (N=176) were recruited at gestational week (GW) T1: 12–22 and categorized into Normal (BMI< 25) or High BMI (BMI > 25). Women attended laboratory sessions at T2: GW 23–28, and T3: GW 34–36 to assess maternal and fetal HR and HR variability (HRV) at baseline and after a stressor at T3. Infant behavior was assessed at 4 months using the Infant Behavior Questionnaire-Revised. Women with high BMI bearing female fetuses had higher HR and lower HRV at both gestational time points. Later in the third trimester, female fetuses of high BMI women exhibited lower HRV when challenged with a stressor. At 4 months, female infants were rated as having lower scores on the Orienting/Regulatory scale. Our findings provide evidence of female sex-specific programming of maternal pre-pregnancy BMI on maternal ANS regulation and neurodevelopment identified in-utero and continuing into early infancy. • Maternal high BMI is linked with changes in prenatal maternal autonomic nervous system functioning moderated by fetal sex. • Maternal high BMI is associated with reduced heart rate variability only female fetuses when exposed to stress challenge. • Maternal high BMI is associated with decreased capacity to regulate behavioral affect at 4 months of age in female infants. [ABSTRACT FROM AUTHOR]

Two separate lines of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity, and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences and environmental exposures. This research considered together raises the intriguing hypothesis first advanced by Pluess and Belsky (Dev Psychopathol 23:29-38, 2011) that prenatal-stress fosters, promotes or "programs" postnatal developmental plasticity. In this paper, we review further evidence consistent with this proposition, including a novel animal study which experimentally manipulated both prenatal stress and postnatal rearing. Directions for future work focused on mechanisms mediating the plasticity-inducing effects of prenatal stress and the moderators of such effects are outlined.

[Display omitted] • Prenatal exposure to cafeteria diet primes anxiety-like behavior in the offspring. • Prenatal exposure to cafeteria diet increased volume in primary somatosensory cortex. • Prenatal exposure to cafeteria diet reduced volume of fimbria-fornix. • Reduced volume of fimbria-fornix correlates with defective white matter integrity. • Cafeteria diet exposure predicts low volume in the fimbria-fornix and anxiety. Prenatal exposure to high-energy diets primes brain alterations that increase the risk of developing behavioral and cognitive failures. Alterations in the structure and connectivity of brain involved in learning and memory performance are found in adult obese murine models and in humans. However, the role of prenatal exposure to high-energy diets in the modulation of the brain's structure and function during cognitive decline remains unknown. We used female C57BL6 mice (n = 10) exposed to a high-energy diets (Cafeteria diet (CAF)) or Chow diet for 9 weeks (before, during and after pregnancy) to characterize their effect on brain structural organization and learning and memory performance in the offspring at two-month-old (n = 17). Memory and learning performance were evaluated using the Y-maze test including forced and spontaneous alternation, novel object recognition (NORT), open field and Barnes maze tests. We found no alterations in the short- or long-time spatial memory performance in male offspring prenatally exposed to CAF diet when compared to the control, but they increased time spent in the edges resembling anxiety-like behavior. By using deformation-based morphometry and diffusion tensor imaging analysis we found that male offspring exposed to CAF diet showed increased volume in primary somatosensory cortex and a reduced volume of fimbria-fornix, which correlate with alterations in its white matter integrity. Biological modeling revealed that prenatal exposure to CAF diet predicts low volume in the fimbria-fornix, which was associated with anxiety in the offspring. The findings suggest that prenatal exposure to high-energy diets prime brain structural alterations related to anxiety in the offspring. [ABSTRACT FROM AUTHOR]

In a wide range of taxa, there is evidence that mothers adaptively shape the development of offspring behaviour by exposing them to steroids. These maternal effects have major implications for fitness because, by shaping early development, they can permanently alter how offspring interact with their environment. However, theory on parent–offspring conflict and recent physiological studies showing that embryos rapidly metabolize maternal steroids have placed doubt on the adaptive significance of these hormone-mediated maternal effects. Reconciling these disparate perspectives requires a mechanistic understanding of the pathways by which maternal steroids can influence neural development. Here, we highlight recent advances in developmental neurobiology and psychiatric pharmacology to show that maternal steroid metabolites can have direct neuro-modulatory effects potentially shaping the development of neural circuitry underlying ecologically relevant behavioural traits. The recognition that maternal steroids can act through a neurosteroid pathway has critical implications for our understanding of the ecology and evolution of steroid-based maternal effects. Overall, compared to the classic view, a neurosteroid mechanism may reduce the evolutionary lability of hormone-mediated maternal effects owing to increased pleiotropic constraints and frequently influence long-term behavioural phenotypes in offspring. [ABSTRACT FROM AUTHOR]

Objective: High maternal folic acid exposure has been studied as a risk factor for child asthma with inconclusive results. Folic acid supplementation that begins before pregnancy may propagate high exposures during pregnancy, particularly in regions with fortified food supplies. We investigated whether folic acid supplementation initiated periconceptionally is associated with childhood asthma in a US cohort. Materials and methods: We re-contacted mother–child dyads previously enrolled in a prospective pregnancy cohort and included children age 4 to 8 years at follow-up (n = 540). Using first trimester interviews, we assessed whether initial folic acid-containing supplement (FACS) use occurred near/before estimated conception ("periconceptional") or after (during the "first trimester"). Follow-up questionnaires were used to determine if a child ever had an asthma diagnosis ("ever asthma") or asthma diagnosis with prevalent symptoms or medication use ("current asthma"). We examined associations between FACS initiation and asthma outcomes using logistic regression, excluding preterm births and adjusting for child age, sex, maternal race, maternal education, and parental asthma. Results: Approximately half of women initiated FACS use periconceptionally (49%). Nine percent of children had "ever asthma" and 6% had "current asthma." Periconceptional initiation was associated with elevated odds of ever asthma [adjusted odds ratio (95% Confidence Interval): 1.65 (0.87, 3.14)] and current asthma [1.87 (0.88, 4.01)], relative to first trimester initiation. Conclusion: We observed positive, but imprecisely estimated associations between periconceptional FACS initiation and child asthma. Folic acid prevents birth defects and is recommended. However, larger studies of folic acid dosing and timing, with consideration for childhood asthma, are needed. [ABSTRACT FROM AUTHOR]

Exposure of avian mothers to stressful conditions permanently alters offspring behavior and physiology. Yet, the effects of maternal stress on the development of offspring immunity in birds remain unclear, particularly in wild species. We injected Eastern bluebird (Sialia sialis) eggs with either a corticosterone or control solution, then measured the impacts on nestling morphology and two measures of immunity, bactericidal capacity and swelling responses to phytohemagglutinin. Nestlings from corticosterone-treated eggs had lower condition indices at hatch but quickly caught up to their control counterparts by Day 5 posthatch and until fledging. Corticosterone-exposed nestlings also mounted smaller swelling responses to phytohemagglutinin, whereas there were no effects on bactericidal capacity. These results indicate that maternal stress can impact offspring immunocompetence, fitness prospects, and potentially their ability to fend off parasites and pathogens., (© 2025 The Author(s). Journal of Experimental Zoology Part A: Ecological and Integrative Physiology published by Wiley Periodicals LLC.)

In this article, I highlight core ideas, empirical findings, and advances in the study of how stress during pregnancy may prenatally program child neurodevelopmental, psychopathological, and health outcomes, emphasizing reviews, metanalyses, and recent contributions of conceptual and empirical work. The article offers a perspective on the history of this area of science, the underrecognized contributions of influential scholars from diverse fields of study, what we know from the evidence to date, the persistent challenges in sorting through what is left to learn, and suggestions for future research. I include sections focused on promoting resilience, pregnancy interventions that demonstrate positive effects across two generations, and the translational implications of the accruing data for practice and policy, highlighting opportunities for integrating across a range of fields and sectors. In the concluding sections, I discuss lessons learned from conducting this work and provide a closing summary of progress and future directions. The goal of this writing was to provide a viewpoint on some ways that emerging intergenerational transmission scholars might responsibly contribute to the future of the field of developmental psychopathology.

Maternal hormones, such as thyroid hormones (THs) transferred to embryos and eggs, are key signaling pathways for mediating maternal effects. To be able to respond to maternal cues, embryos must express the key molecular “machinery” of hormone pathways, such as enzymes and receptors. While altricial birds begin TH production only at or after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited into the egg. However, it is not understood how or when altricial birds express genes in the TH pathway. For the first time, we measured the expression of key TH-pathway genes in altricial embryos by using two common altricial ecological model species, pied flycatcher (Ficedula hypoleuca) and blue tit (Cyanistes caeruleus). Deiodinase DIO1 gene expression could not be reliably confirmed in either species, but deiodinase enzyme genes DIO2 and DIO3 were expressed in both species. Given that DIO2 converts thyroxine to biologically active triiodothyronine and that DIO3 mostly converts triiodothyronine to inactive forms of THs, our results suggest that embryos may modulate maternal signals. TH receptors (THRA and THRB) and a monocarboxylate membrane transporter gene (SLC16A2) were also expressed, enabling TH responses. Our results suggest that altricial embryos may be able to respond to and potentially modulate maternal signals conveyed by THs in early development. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is associated with pregnancy complications, such as preeclampsia, placental abruption, and gestational sleep apnea. Hypoxic insults during gestation can impact the brain maturation of cortical and subcortical pathways, such as the nigrostriatal pathway. However, the long-term effects of in utero hypoxic stress exposure on brain maturation in offspring are unclear, especially exposure during late gestation. The purpose of this study was to determine the impact of gestational hypoxia in late pregnancy on developmental programming of subcortical brain maturation by focusing on the nigrostriatal pathway. Methods: Timed pregnant Long–Evans rats were exposed to chronic intermittent hypoxia or room air normoxia from gestational day (GD) 15–19 (term 22–23 days). Male and female offspring were assessed during two critical periods: puberty from postnatal day (PND) 40–45 or young adulthood (PND 60–65). Brain maturation was quantified by examining (1) the structural development of the nigrostriatal pathway via analysis of locomotor behaviors and the substantia nigra dopaminergic neuronal cell bodies and (2) the refinement of the nigrostriatal pathway by quantifying ultrasonic vocalizations (USVs). Results: The major findings of this study are gestational hypoxia has age- and sex-dependent effects on subcortical brain maturation in offspring by adversely impacting the refinement of the nigrostriatal pathway in the absence of any effects on the structural development of the pathway. During puberty, female offspring were impacted more than male offspring, as evidenced by decreased USV call frequency, chirp USV call duration, and simple call frequency. In contrast, male offspring were impacted more than female offspring during young adulthood, as evidenced by increased latency to first USV, decreased simple USV call intensity, and increased harmonic USV call bandwidth. No effects of gestational hypoxia on the structural development of the nigrostriatal pathway were observed. Conclusions: These novel findings demonstrate hypoxic insults during pregnancy mediate developmental programming of the cortical and subcortical pathways, in which male offspring exhibit long-term adverse effects compared to female offspring. Impairment of cortical and subcortical pathways maturation, such as the nigrostriatal pathway, may increase risk for neuropsychiatric disorders (e.g., mood disorders, cognitive dysfunction, brain connectivity dysfunction). Highlights: Brain maturation of the nigrostriatal pathway is sex- and age- dependent. Exposure to hypoxia in late pregnancy impacts brain maturation of the nigrostriatal pathway that can be observed during puberty and young adulthood. Gestational hypoxia impacted female offspring during puberty more than males, whereas it impacted male offspring during young adulthood more than females. These novel findings demonstrate that hypoxic insults during pregnancy mediate developmental programming of the cortical and subcortical pathways, in which male offspring exhibit long-term adverse effects compared to female offspring. Long-term adverse effects of gestational hypoxia in offspring can occur in the absence of pregnancy complications, especially if they occur within critical embryological developmental periods. [ABSTRACT FROM AUTHOR]

Simple Summary: Parental obesity affects skeletal metabolism in offspring. This relationship is called "nutritional programming". During the weaning period, they are more highly mineralized and mechanically resistant. It was interesting for us whether changing or continuing the feeding of male offspring with a standard or high-energy diet may have different metabolic effects on bone tissue. Our previous studies on females have shown that the beneficial direction of change is the replacement of the standard diet with a high-energy diet; the reduction of the caloric content of food (change from a high-energy to a properly balanced diet) leads to disorders of skeletal growth and development. In males, any change in diet inhibited skeletal development, and the bones were weaker. The most effective was the continuation of high-energy nutrition, which, in males at 49 and 90 days of age, was manifested by stronger bones. This proves that males and females react differently to a change in the caloric content of the diet during the period of growth and development. The experiment was undertaken to assess whether the continuation or change of the parents' diet affects the previously programmed bone metabolism of the male offspring during its growth and development. A total of 16 male and 32 female Wistar rats were divided into groups and fed a standard (diet S) or high-energy (diet F). After the induction of obesity, the rats from groups S and F, as the parent generation, were used to obtain male offspring, which were kept with their mothers until the weaning day (21 days of age). In our earlier study, we documented the programming effects of the diet used in parents on the skeletal system of offspring measured on the weaning day. Weaned male offspring constitute one control group—parents and offspring fed the S diet. There were three experimental groups, where: parents received diet S and offspring were fed with the F diet; parents were treated with the diet F, while offspring received the S diet; and parents and offspring were fed with the diet F. The analyses were performed at 49 and 90 days of life. After sacrifice, cleaned-off soft tissue femora were assessed using peripheral quantitative computed tomography (pQCT), dual X-ray absorptiometry (DXA), and a three-point bending test. We observed that changing and continuation of nutrition, applied previously in parents, significantly influenced the metabolism of the bone tissue in male offspring, and the osteotropic effects differed, depending on the character of the nutrition modification and age. Additionally, an important conclusion of our study, regarding the previous, is that nutrition modification, affecting the metabolism of bone tissue, also depends on the sex. [ABSTRACT FROM AUTHOR]

First-degree male relatives of polycystic ovary syndrome (PCOS) sufferers can develop metabolic abnormalities evidenced by elevated circulating cholesterol and triglycerides, suggestive of a male PCOS equivalent. Similarly, male sheep overexposed to excess androgens in fetal life develop dyslipidaemia in adolescence. Dyslipidaemia, altered lipid metabolism, and dysfunctional hepatic mitochondria are associated with the development of non-alcoholic liver disease (NAFLD). We therefore dissected hepatic mitochondrial function and lipid metabolism in adolescent prenatally androgenized (PA) males from an ovine model of PCOS. Testosterone was directly administered to male ovine fetuses to create prenatal androgenic overexposure. Liver RNA sequencing and proteomics occurred at 6 months of age. Hepatic lipids, glycogen, ATP, reactive oxygen species (ROS), DNA damage, and collagen were assessed. Adolescent PA males had an increased accumulation of hepatic cholesterol and glycogen, together with perturbed glucose and fatty acid metabolism, mitochondrial dysfunction, with altered mitochondrial transport, decreased oxidative phosphorylation and ATP synthesis, and impaired mitophagy. Mitochondrial dysfunction in PA males was associated with increased hepatic ROS level and signs of early liver fibrosis, with clinical relevance to NAFLD progression. We conclude that excess in utero androgen exposure in male fetuses leads to a PCOS-like metabolic phenotype with dysregulated mitochondrial function and likely lifelong health sequelae. [ABSTRACT FROM AUTHOR]