It was reported that high blood cholesterol levels increased the susceptibility to mitochondrial dysfunction. This study hypothesized that the gestational hypercholesterolemia (HC) could induce the mitochondrial dysfunction in term human placenta. The eligible pregnant women were recruited from Xuanwu Hospital in Beijing during their first prenatal visit (before their 10th week of pregnancy). In total, 19 pregnant women whose serum total cholesterol levels were higher than 7.25 mm at third trimester (measured at 36–38 weeks) were selected as gestational HC. Other 19 pregnant women with normal cholesterol level matched with age, pre-gestational body mass index, and the neonatal gender were included as the control group. Full-term placenta samples were collected. The mitochondrial DNA (mtDNA) copy number, messenger RNA (mRNA) expression of cytochrome c oxidase subunit I, adenosine triphosphate monophosphatase 6 (ATP6ase), citrate synthase, peroxisome proliferator-activated receptor-γ (PPARγ) co-activator 1α, PPARγ co-activator 1β and estrogen-related receptor-α, and the activity of mitochondrial respiratory chain enzyme complex were measured. Pregnancy outcomes were obtained by extraction from medical records and the labor ward register. The results showed that only placental mtDNA copy number and mRNA expression of ATP6ase were significantly decreased in HC group. No significant differences were detected of other measurements between the two groups. These findings indicated that gestational HC might not induce the damage of placental function seriously.

Elevated levels of organochlorines (OC) have been reported in Inuit populations in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC mixture adversely affects male reproductive function and health with age. Sprague–Dawley female rats (F0) were gavaged with an environmentally relevant concentration of an Arctic OC mixture or corn oil (Control) during mating with untreated males until parturition (F1 litters). After postnatal day (PND) 90, the weights of the OC F1 males differed dramatically relative to Controls (P<0.05; n=10) and they exhibited respiratory distress. Except for possible thinning of the alveolar barrier, histological observation of the lungs revealed no apparent pathology to explain the respiratory distress. At PND 365, OC F1 males had reduced relative reproductive organ weights and lower sperm quality than Controls (P<0.05). At PND 90, OC F1 males were subfertile (P<0.05), but were infertile at PND 365. In conclusion, environmentally relevant prenatal OC exposure reduced reproductive function and health in aging male rats, providing new insight into the effects of early-life exposures to these contaminants.

Placental structure and function determine birth outcomes. Placental mass does not always correlate with fetal birth weight (BW) in uncomplicated pregnancies which raises the possibility of other variables such as placental shape and cord insertion being the determinants of placental efficiency. In total, 160 women with singleton pregnancy, recruited into a pregnancy cohort were studied. Placental weight (PW) was measured and other data were obtained from clinical records. Birth outcomes were classified as small for gestational age (SGA) and appropriate for gestational age (AGA) based on fetal gender, gestational age (GA) and BW. High-resolution images of the chorionic plate were recorded. The shape of the placenta and the insertion of the cord were measured using eccentricity index (EI) and cord centrality index (CCI). Only placentae with eccentrically inserted cords (n=136) were included. The mean BW and PW were 2942 (±435) g and 414 (±82) g with average GA of 38.6 weeks. The mean CCI and EI was 0.483 (±0.17) and 0.482 (±0.16). Neither of these correlated with placental efficiency. However, EI showed negative correlation with placental surface area and breadth. Upon sub-grouping the cohort into SGA (n=32) and AGA (n=104), the SGA babies with the highest EI (third tertile) had significantly lower BW than those with the least eccentric placentae (first tertile). Although eccentric-shaped placentae were present in both SGA and AGA groups, the effect on BW was observed only in the SGA group.

With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student’s t-test and Mann–Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.

Longitudinal maternal mental health data are needed from high HIV prevalence settings. The Siyakhula Cohort (SC) is a population-based cohort of HIV-positive and negative mothers (n=1506) with HIV-negative children (n=1536) from rural South Africa. SC includes 767 HIV-negative mothers; 465 HIV-positive in pregnancy; 272 HIV-positive since pregnancy (n=2 missing HIV status). A subgroup (n=890) participated in a non-randomized breastfeeding intervention [Vertical Transmission Study (VTS)]; the remaining (n=616) were resident in the same area and received antenatal care at the time of the VTS, but were not part of the VTS, instead receiving the standard of care Prevention of Mother-to-Child Transmission (PMTCT) Programme. In secondary analysis we investigated the prevalence of, and factors associated with, psychological morbidity amongst mothers who were still the primary caregiver of the child (1265 out of 1506) at follow-up (7–11 years post-birth). We measured maternal depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder Scale-7) and parenting stress (Parenting Stress Index-36), using standardized cut-offs and algorithms. In total, 75 (5.9%) mothers met criteria for depression, 37 (2.9%) anxiety and 134 (10.6%) parenting stress. Using complete case logistic regression (n=1206 out of 1265 mothers) as compared to being HIV-negative, testing HIV-positive in pregnancy doubled odds of depression [adjusted odd ratios (aOR)=1.96 [1.0–3.7] P=0.039]. Parenting stress was positively associated with acquisition of HIV after pregnancy (aOR=3.11 [1.9–5.2] P<0.001) and exposure to household crime (aOR=2.02 [1.3–3.2] P=0.003); negatively associated with higher maternal education (aOR=0.29 [0.1–0.8] P=0.014), maternal employment (aOR=0.55 [0.3–0.9] P=0.024). Compared with the standard of care PMTCT, VTS mothers had reduced odds of parenting stress (aOR=0.61 [0.4–0.9] P=0.016). Integrating parental support into mostly bio-medical treatment programmes, during and beyond pregnancy, is important.

The aim of the present work was to address experimentally the possible impact of exposure to air pollution during gestation on the differentiation and function of the gonads of the offspring using a rabbit model. Rabbits were exposed daily to diluted diesel exhaust gas or filtered air from the 3rd until the 27th day of gestation, during which time germ cells migrate in genital ridges and divide, and fetal sex is determined. Offspring gonads were collected shortly before birth (28th day of gestation) or after puberty (7.5 months after birth). The structure of the gonads was analyzed by histological and immunohistological methods. Serum concentrations of testosterone and anti-Müllerian hormone were determined using ELISA. The morphology and the endocrine function of the gonads collected just at the arrest of the exposure were similar in polluted and control animals in both sexes. No differences were observed as well in gonads collected after puberty. Sperm was collected at the head of the epididymis in adults. Sperm motility and DNA fragmentation were measured. Among all parameters analyzed, only the sperm DNA fragmentation rate was increased three-fold in exposed males. Mechanisms responsible for these modifications and their physiological consequences are to be further clarified.

Experimental data have suggested that some contaminants in the environment may increase the risk of obesity. Infants can be exposed to chemicals either prenatally, by trans-placental passage of chemicals, or postnatally by their own diet and by other external pathways (air inhalation, dust, hand-to-mouth exposure) after birth. To provide a review of epidemiological evidence on the association between prenatal exposure to chemicals and prenatal and postnatal growth, we present the literature from systematic review articles and international meta-analyses, when available, or recent research articles when summarizing articles were not available. The most studied contaminants in this field were persistent organic pollutants (e.g. organochlorinated pesticides, polychlorinated biphenyls), non-persistent pollutants (e.g. phthalates, bisphenol A), toxic heavy metals (i.e. cadmium, lead and mercury), arsenic, mycotoxins and acrylamide. Mounting evidence suggests that child’s growth may be associated with prenatal or postnatal exposures to environmental contaminants. Improving exposure assessment and studying the contaminants as mixtures should allow to gain knowledge about the environmental determinants of growth and obesity.

Lead is one of the environmental pollutants with cardiovascular toxicity. The embryos are particularly sensitive to lead exposure, because it can move through the blood-placental barrier and the blood-brain barrier easily during embryonic development. Cerebral cavernous malformations 3 (CCM3) gene plays an important role in cardiovascular development, mainly affecting cell proliferation, differentiation and apoptosis. In this study, we established a blood vessel development model of mouse embryos in order to imitate human people with CCM3 genes defects and exposing to environment toxin Pb in utero. We would like to determine the interaction of Pb and CCM3 gene on vascular development, and to explore the mechanisms. We found that the yolk sac of CCM3 heterozygous mice embryo showed abnormal morphology at E11.5 after lead treatment comparing with wild type (WT) mice without lead exposure, meanwhile it showed more angiogenesis and vascular remodeling in the hematoxylin and eosin stained sections of the CCM3+/− yolk sac with lead exposure. We also found that the similar effect of Pb and CCM3 gene on mitochondrial DNA (mtDNA) copy number in vivo and in vitro. Mitochondrial morphology and function also changed in primary human umbilical vein endothelial cells after lead exposure. Besides, it was found that the HIF-1α and TFAM which have close relationship with mtDNA biogenesis showed similarly increasing messenger RNA expression in both human and mouse-derived primary cells with lead treated and CCM3 gene knockout. All of the above results indicated that lead and CCM3 might damage endothelial cells through mitochondria pathway and eventually both affected angiogenesis.

The effect of maternal Ramadan-type fasting (RTF) on the outcome of pregnancy, kidney development and nephron number in male rat offspring was investigated in current study. Pregnant rats were given food and water ad libitum during pregnancy (control) or restricted for 16 h per day (RTF). Kidney structure was examined during fetal life, at birth, and in early and late adulthood. Maternal body weight, food intake, relative food intake and plasma glucose levels were significantly lower (P<0.001) in the RTF group. Litter and pup weights also were significantly lower (P<0.05) in the RTF group at birth, with no difference in the litter size. The RTF group had a longer gestation, delayed nephrogenesis with less well-differentiated glomeruli, more connective tissue, fewer medullary rays, an increase in the nephrogenic zone/cortical zone ratio, and significant increase (P<0.001) in kidney apoptosis at birth. On the other hand, maternal fasting reduced nephron number (by ~31%) with unchanged kidney and total glomerular volumes. Mean glomerular volume was significantly higher in RTF offspring. Assessment of renal structure revealed mild glomerulosclerosis with enlarged lobulated glomeruli in the renal cortex and high interstitial fibrosis in the medulla of RTF kidneys. Taken together, gestational fasting delays nephrogenesis and reduces nephron number in the kidneys of the offspring, that could be partially owing to increased apoptosis.

Nutrition during pregnancy and lactation is a critical factor in the development of the offspring. Both protein content and source in maternal diet affect neonatal health, but the long-term effects of maternal low-quality protein diet on the offspring are less clear. This study aimed to examine the effects of maternal low-quality protein diet on offspring’s growth, development, circulating metabolites and hepatic expression of methyltransferases. Virgin Wistar rats were mated at 11 weeks of age. Dams were then maintained on either a chow diet with 20% casein as the control group (C), or a low-quality protein diet with 20% wheat gluten as the experimental group (WG) throughout gestation and lactation. After weaning, all offspring were fed a control chow diet until the age of 20 weeks. Male WG offspring had significantly lower body weight and energy intake, whereas female WG offspring had significantly higher body weight and energy intake when compared with controls. Early life exposure to WG diet had no significant effect on circulating metabolites. However, fasting insulin concentrations and homoeostasis model assessment-insulin resistance were decreased in WG male and female offspring. Maternal low-quality protein diet increased plasma aspartic acid, glutamic acid, histidine, cystathione and decreased lysine in male WG offspring. Conversely, the same amino acids were reduced in female WG offspring. Adult offspring exposed to WG diet had significantly upregulated hepatic DNMT3a and DNMT3b expressions. Our study showed that there were differential effects of maternal poor-quality protein diet upon adult offspring’s metabolism.

Insights from the Developmental Origins of Health and Disease paradigm and epigenetics are elucidating the biological pathways through which social and environmental signals affect human health. These insights prompt a serious debate about how the structure of society affects health and what the responsibility of society is to counteract health inequalities. Unfortunately, oversimplified interpretations of insights from Developmental Origins of Health and Disease and epigenetics may be (mis)used to focus on the importance of individual responsibility for health rather than the social responsibility for health. In order to advance the debate on responsibility for health, we present an ethical framework to determine the social responsibility to counteract health inequalities. This is particularly important in a time where individual responsibility often justifies a passive response from policymakers.

Macrosomia, not only is closely associated with short-term, birth-related problems, but also has long-term consequences for the offspring. We investigated the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the placenta of macrosomia births using a microarray profile. The data showed that 2929 lncRNAs and 4574 mRNAs were upregulated in the placenta of macrosomia births compared with the normal birth weight group (fold change ⩾2.0, P<0.05), and 2127 lncRNAs and 2511 mRNAs were downregulated (fold change ⩾2.0, P<0.05). To detect the function of the differentially expressed lncRNAs and their possible relationship with the differentially expressed mRNAs, we also performed gene ontology analysis and pathway analysis. The results demonstrated that the PI3K-AKT signalling pathway, the mitogen-activated protein kinase (MAPK) signalling pathway, the focal adhesion pathway, the B cell receptor signalling pathway, and the protein processing in endoplasmic reticulum and lysosome pathway were significantly differentially expressed in the macrosomia placenta. Four lncRNAs were randomly chosen from the differentially expressed lncRNAs to validate the microarray data by quantitative polymerase chain reaction (qPCR). The qPCR results were consistent with the microarray data. In conclusion, lncRNAs were significantly differentially expressed in the placenta of macrosomia patients, and may contribute to the pathogenesis of macrosomia.

Non-communicable diseases (NCDs) are a major problem as they are the leading cause of death and represent a substantial economic cost. The ‘Developmental Origins of Health and Disease Hypothesis’ proposes that adverse stimuli at different life stages can increase the predisposition to these diseases. In fact, adverse in utero programming is a major origin of these diseases due to the high malleability of embryonic development. This review provides a comprehensive analysis of the scientific literature on in utero programming and NCDs highlighting potential medical strategies to prevent these diseases based upon this programming. We fully address the concept and mechanisms involved in this programming (anatomical disruptions, epigenetic modifications and microbiota alterations). We also examine the negative role of in utero programming on the increased predisposition of NCDs in the offspring, which introduces the passive medical approach that consists of avoiding adverse stimuli including an unhealthy diet and environmental chemicals. Finally, we extensively discuss active medical approaches that target the causes of NCDs and have the potential to significantly and rapidly reduce the incidence of NCDs. These approaches can be classified as direct in utero programming modifications and personalized lifestyle pregnancy programs; they could potentially provide transgenerational NCDs protection. Active strategies against NCDs constitute a promising tool for the reduction in NCDs.

Previous studies have shown that the renin–angiotensin system (RAS) is affected by adverse maternal nutrition during pregnancy. The aim of this study was to investigate the effects of a maternal low-protein diet on proinflammatory cytokines, reactive oxygen species and RAS components in kidney samples isolated from adult male offspring. We hypothesized that post-weaning losartan treatment would have beneficial effects on RAS activity and inflammatory and oxidative stress markers in these animals. Pregnant Sprague–Dawley rats were fed with a control (20% casein) or low-protein diet (LP) (6% casein) throughout gestation. After weaning, the LP pups were randomly assigned to LP and LP-losartan groups (AT1 receptor blockade: 10 mg/kg/day until 20 weeks of age). At 20 weeks of age, blood pressure levels were higher and renal RAS was activated in the LP group. We also observed several adverse effects in the kidneys of the LP group, including a higher number of CD3, CD68 and proliferating cell nuclear antigen-positive cells and higher levels of collagen and reactive oxygen species in the kidney. Further, our results revealed that post-weaning losartan treatment completely abolished immune cell infiltration and intrarenal RAS activation in the kidneys of LP rats. The prevention of augmentation of angiotensin (Ang II) concentration abolished inflammatory and fibrotic events, indicating that Ang II via the AT1 receptor is essential for pathological initiation. Our results suggest that the prenatal programming of hypertension is dependent on the up-regulation of local RAS and presence of immune cells in the kidney.

Growth restriction caused by postnatal undernutrition increases risk for cardiovascular disease in adulthood with the potential to induce arrhythmogenesis. Thus, the purpose was to determine if undernutrition during development produced arrhythmias at rest and when stressed with dobutamine in adulthood. Mouse dams were fed (CON: 20% protein), or low-protein (LP: 8%) diet before mating. A cross-fostering model was used where pups nursed by dams fed LP diet in early [EUN; postnatal day (PN) 1–10], late (LUN; PN11–21) and whole (PUN; 1–21) phases of postnatal life. Weaned pups were switched to CON diets for the remainder of the study (PN80). At PN80, body composition (magnetic resonance imaging), and quantitative electrocardiogram (ECG) measurements were obtained under 1% isoflurane anesthesia. After baseline ECG, an IP injection (1.5 µg/g body weight) of dobutamine was administered and ECG repeated. Undernutrition significantly (P<0.05) reduced body weight in LUN (22.68±0.88 g) and PUN (19.96±0.32 g) but not in CON (25.05±0.96 g) and EUN (25.28±0.9207 g). Fat mass decreased in all groups compared with controls (CON: 8.00±1.2 g, EUN: 6.32±0.65 g, LUN: 5.11±1.1 g, PUN: 3.90±0.25 g). Lean mass was only significantly reduced in PUN (CON: 17.99±0.26 g, EUN: 17.78±0.39 g, LUN: 17.34±0.33 g, PUN: 15.85±0.28 g). Absolute heart weights were significantly less from CON, with PUN having the smallest. ECG showed LUN had occurrences of atrial fibrillation; EUN had increases of 1st degree atrioventricular block upon stimulation, and PUN had increased risk for ventricular depolarization arrhythmias. CON did not display arrhythmias. Undernutrition in early life resulted in ventricular arrhythmias under stressed conditions, but undernutrition occurring in later postnatal life there is an increased incidence of atrial arrhythmias.

The immune system not only provides protection against infectious disease but also contributes to the etiology of neoplastic, atopic, and cardiovascular and metabolic diseases. Prenatal and postnatal nutritional and microbial environments have lasting effects on multiple aspects of immunity, indicating that immune processes may play important roles in the developmental origins of disease. The objective of this study is to evaluate the association between birth weight and the distribution of leukocyte (white blood cell) subsets in peripheral blood in young adulthood. Postnatal microbial exposures were also considered as predictors of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn from a prospective birth cohort study in the Philippines, and analyses focused on the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, natural killer cells, monocytes, granulocytes. Higher birth weight was a strong predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041, P=0.003), lower proportion of CD8 T lymphocytes (B=−0.874, s.e.=0.364, P=0.016), higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were negatively associated with proportions of B lymphocytes and granulocytes, and lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate and specific immunity, but the origins of variation in the distribution of cell type across individuals are not known. Our findings point toward nutritional and microbial exposures in infancy as potentially important determinants of immune-phenotypes in adulthood, and they suggest that leukocyte distribution is a plausible mechanism through which developmental environments have lasting effects on disease risk in adulthood.

Several studies have suggested that maternal lifestyle during pregnancy may influence long-term health of offspring by altering the offspring epigenome. Whether maternal leisure-time physical activity (LTPA) during pregnancy might have this effect is unknown. The purpose of this study was to determine the relationship between maternal LTPA during pregnancy and offspring DNA methylation. Participants were recruited from the Archive for Research on Child Health study. At enrollment, participants’ demographic information and self-reported LTPA during pregnancy were determined. High active participants (averaged 637.5 min per week of LTPA; n=14) were matched by age and race to low active participants (averaged 59.5 min per week LTPA; n=28). Blood spots were obtained at birth. Pyrosequencing was used to determine methylation levels of long interspersed nucleotide elements (LINE-1) (global methylation) and peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), insulin-like growth factor 2 (IGF2), pyruvate dehydrogenase kinase, isozyme 4 (PDK4) and transcription factor 7-like 2 (TCF7L2). We found no differences between offspring of high active and low active groups for LINE-1 methylation. The only differences in candidate gene methylation between groups were at two CpG sites in the P2 promoter of IGF2; the offspring of low active group had significantly higher DNA methylation (74.70±2.25% methylation for low active v. 72.83±2.85% methylation for high active; P=0.045). Our results suggest no effect of maternal LTPA on offspring global and candidate gene methylation, with the exception of IGF2. IGF2 has been previously associated with regulation of physical activity, suggesting a possible role of maternal LTPA on regulation of offspring physical activity.

Exercise during pregnancy has beneficial effects on maternal and offspring’s health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring’s weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.

There is limited evidence on the association between maternal preconception body mass index (BMI) trajectories and pregnancy complications and child development. This study examined the relationships of maternal BMI trajectories, diabetes and hypertensive disorders during pregnancy and offspring’s childhood physical and cognitive development. Data were from the Australian Longitudinal Study on Women’s Health and the Mothers and their Children’s Health study (n=771). Women’s preconception BMI trajectories were identified using group-based trajectory modelling. Children’s physical and cognitive development (up to the average age of 5 years) were obtained from the Ages and Stages Questionnaire (suspected gross motor delay) and the Australian Early Development Census (AEDC). Generalized estimating equation models, adjusted for maternal sociodemographic and lifestyle factors, were used for analyses. Three distinct BMI trajectories were identified (normative, chronically overweight and chronically obese). Children born to chronically obese women were more likely to be classified as developmentally vulnerable/at-risk on AEDC domains; gross and fine motor skills [risk ratio (RR)=1.64, 95% confidence interval (CI): 1.04, 2.61] and communication skills and general knowledge (RR=1.71, 95% CI: 1.09, 2.68). They also had an elevated risk of suspected gross motor delay (RR=2.62, 95% CI: 1.26, 5.44) compared with children born to women with a normative BMI trajectory. Maternal diabetes or hypertensive disorders during pregnancy were not associated with child outcomes. Maternal preconception BMI trajectories were associated with poorer childhood development. This study finding underscores the importance of excessive weight gain prevention throughout the reproductive stage of life.

Animal evidence has suggested that maternal emotional and nutritional stress during pregnancy is associated with behavioral outcomes in offspring. The nature of the stresses applied may differ, but it is often assumed that the mother’s hippocampus–hypothalamic–pituitary–adrenal (HHPA) axis response releases higher levels of glucocorticoid hormones. The bed nucleus of the stria terminalis (BNST) is in a pivotal position to regulate the HHPA axis and the stress response, and it has been implicated in anxiety behavior. In the current study, to search whether BNST structural changes and neurochemical alterations are associated with anxiety-related behavior in adult gestational protein-restricted offspring relative to an age-matched normal protein diet (NP) rats, we conduct behavioral tests and, BNST dendritic tree analysis by Sholl analysis, associated to immunoblotting–protein quantification [11β-HSD2, GR, MR, AT1R, 5HT1A and 5HT2A, corticotrophin-releasing factor (CRH) and CRH1]. Dams were maintained either on isocaloric standard rodent chow [with NP content, 17% casein or low protein content (LP), 6% casein] chow throughout their entire pregnancy. Here, in rats subjected to gestational protein restriction, we found: (a) a significant reduction in dendritic length and impoverished dendritic arborization in BNST neurons; (b) an elevated plasmatic corticosterone levels; and (c) associated with enhanced anxiety-like behavior when compared with age-matched NP offspring. Moreover, altered protein (11β-HSD2, GR, MR and type 1 CRH receptors) expressions may underlie the increase in anxiety-like behavior in LP offspring. This work represents the first demonstration that BNST developmental plasticity by maternal protein restriction, resulting in fine structural changes and neurochemical alterations that are associated with modified behavioral states.