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Maternal nutrition is one of the main environmental factors regulating gene expression during fetal development through epigenetic modifications. Some nutrients, such as the amino acid l -arginine, are added to maternal diets to modulate gene expression, improve the reproductive performance of females, and enhance conceptus development. This study investigated the hypothesis that supplementation of pregnant gilts with l -arginine regulates gene expression in conceptuses through epigenetic mechanisms. For this, fetal programming phenotypic markers, the expression of key epigenetic genes, and the abundance of DNA methylation proteins (DNMT3A and DNMT1) were evaluated in 25- and 35-day conceptuses from gilts supplemented (ARG) or not (CON) with 1.0 % l -arginine during early gestation. At 25 days, there were no significant differences in phenotypic markers between CON and ARG embryos (P > 0.05). Similarly, no differences were found between CON and ARG fetuses at 35 days (P > 0.05). Maternal supplementation with l -arginine did not influence the expression of the evaluated key epigenetic genes in pig embryos or fetuses, nor DNMT3A protein abundance (P > 0.05); on the other hand, DNMT1 protein abundance was lower in ARG fetuses (P = 0.002). It is concluded that supplementation of l -arginine in pregnant gilts affects epigenetic mechanisms, such as DNA methylation, in 35-day fetuses through regulation of DNMT1 levels. Further studies using transcriptomic and proteomic analysis could reveal additional epigenetic modifications in embryos and fetuses following maternal supplementation with l -arginine. • Effects of L-arginine supplementation of sows were evaluated on pig conceptuses. • Genes associated with epigenetic modifications in swine conceptuses were evaluated. • Proteins related to epigenetic modifications in swine conceptuses were quantified. • Sows L-arginine supplementation affected the abundance of DNMT1 protein in fetuses. [ABSTRACT FROM AUTHOR]

This study evaluated different herbage allowances from mid to late pregnancy on pre- and postpartum physiological responses, milk production, and the performance of Nellore cows and the preweaning growth of their female offspring. Sixty multiparous Nellore cows were blocked by their body weight (BW; 425 ± 36 kg) and body condition score (BCS; 3.67 ± 0.23, scale 1–5) and randomly allocated to twelve pastures. Treatments consisted of two different herbage allowances (HA) during pregnancy: low HA (LHA; 2.80 kg DM/kg of BW) and high HA (HHA; 7.60 kg DM/kg of BW). Both treatment groups were fed 1 g/kg BW of a protein supplement. After calving, all cow–calf pairs were combined in a single group. The effects of maternal treatment × day of the study were detected for herbage mass and allowance, the stocking rate and forage crude protein, and for cow BW, BCS, and carcass measures (p < 0.01). Milk yield corrected to 4% fat, while the levels of fat total solids and cow plasma IGF-1 and urea were different (p ≤ 0.04) between treatments. HHA offspring was heavier (p ≤ 0.05) at 120 days and at weaning. A high herbage allowance can be implemented from mid-gestation until calving to increase cow prepartum performance, post-partum milk yield and composition, and positively modulate female offspring preweaning growth.

ScopeThe fetal programming paradigm posits that the origins of obesity can be traced, in part, to the intrauterine period of life. However, the mechanisms underlying fetal programming are not well understood, and few studies have measured offspring adiposity in the neonatal period. The aim of this study is to identify maternal metabolites, and their determinants, that are associated with neonatal adiposity.Methods and resultsA targeted metabolomics approach is applied to analyze plasma samples collected across gestation from a well-characterized cohort of 253 pregnant women participating in a prospective study at the University of California, Irvine. Whole-body dual X-ray absorptiometry (DXA) imaging of body composition is obtained in N = 121 newborns. Statistical models are adjusted for potential confounders and multiple testing. The authors identify six alkyl-linked phosphatidylcholines (PCae), containing fatty acid 20:4, that are significantly and negatively associated with neonatal body fat percentage. Factors indicating higher socioeconomic status, non-Hispanic ethnicity, and higher nonesterified fatty acid percentages are positively associated with these PCae.ConclusionsThe polyunsaturated fatty acid 20:4 contained in PCae may exert a beneficial effect with respect to future propensity for obesity development. Prepregnancy and early pregnancy factors are determinants of these PCae, highlighting the importance of addressing preconceptional conditions for fetal programming of newborn adiposity.

Growing evidence supports an important role for the intrauterine environment in shaping fetal development and subsequent child health and disease risk. The fetal brain is particularly plastic, whereby even subtle changes in structure and function produced by in utero conditions can have long-term implications. Based on the consideration that conditions related to energy substrate and likelihood of survival to reproductive age are particularly salient drivers of fetal programming, maternal nutrition and stress represent the most commonly, but independently, studied factors in this context. However, the effects of maternal nutrition and stress are context dependent and may be moderated by one another. Studies examining the effects of the bidirectional nutrition-stress interplay in pregnancy on fetal programming of brain development are beginning to emerge in the literature. This review incorporates all currently available animal and human studies of this interplay and provides a synthesis and critical discussion of findings. Nine of the 10 studies included here assessed nutrition-stress interactions and offspring neurodevelopmental or brain development outcomes. Despite significant heterogeneity in study design and methodology, two broad patterns of results emerge to suggest that the effects of prenatal stress on various aspects of brain development may be mitigated by 1) higher fat diets or increased intake and/or status of specific dietary fats and 2) higher dietary intake or supplementation of targeted nutrients. The limitations of these studies are discussed, and recommendations are provided for future research to expand on this important area of fetal programming of brain development.

IntroductionBoars are often housed in stressful environments on commercial farms, experiencing poor welfare. These conditions may cause epigenetic changes in the boars' gametes, which could potentially be transmitted to their offspring. We aimed to investigate the effect of three different boars housing environments on the survival, aggression, and nociceptive responses of their offspring.MethodsFor four weeks, 18 boars were housed in three different systems: crates (C;n=6), pens (P;n=6), and enriched pens (E;n=6). The environmental enrichment was provided twice daily (brushing, shower, and hay). Thirteen gilts were housed in outdoor paddocks and inseminated with pooled semen from the boars kept in the three treatments. We evaluated the number of live-born, stillborn, and weaned piglets, sex, and mortality rate. Weaning was performed at 29 days of age. For each piglet, six body photographs were taken for five days postweaning to measure skin lesions (n=138). On Day 34, the nociceptive pressure threshold was assessed using an analgesimeter (n=138). DNA paternity tests were carried out at the end of the study (n=181). A generalized linear model with a negative binomial distribution was used to compare the number of live-born/weaned piglets and skin lesions among the treatment groups. We used a Kruskal‒Wallis test to analyze nociceptive data.ResultsMore live-born and weaned piglets were fathered from boars kept in the E group than the P group (p=0.002;p=0.001, respectively). A trend was observed in the number of skin lesions on the left side of piglets (PE>C;p

IntroductionExcessive maternal lipid mobilization in late gestation may impact the immune function of the newborn. However, the long-term effects remain unknown. The objective was to explore associations between excessive maternal lipid mobilization in the last 2 weeks of gestation with offspring health and performance.MethodsA retrospective study was performed including 1,511 calves (heifer = 692, bull = 819) born between 2015 and 2020 in one MI farm. Plasma non-esterified fatty acids (NEFA) was measured from cows 7 to 14 d before calving. Calves were categorized in 2 groups based NEFA concentration: physiological lipid mobilization (PLM = 1,373; NEFA

Growing evidence identifies maternal adiposity as a potentially modifiable risk factor for adverse neurodevelopment. This retrospective cohort analysis examined whether maternal prepregnancy adiposity and gestational weight gain were associated with behavioral outcomes in 173 rhesus macaque infants at the California National Primate Research Center. Dams conceived indoors, had uncomplicated pregnancies, delivered vaginally, and reared infants indoors. Infants underwent standardized biobehavioral analysis at 90-120 days of age from 3/2001-5/2015. Offspring of mothers with greater baseline adiposity or gestational weight gain exhibited a pattern of poor adaptability characterized by greater emotionality as the assessments proceeded, blunted affective response to a human intruder challenge, and reduced interest in novel stimuli which is associated with poorer social functioning later in life. They also had lower cortisol levels following dexamethasone suppression, perhaps a response to cortisol excess during gestation. These results amplify growing public health concerns implicating maternal adiposity in impaired fetal neurobehavioral programming.

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

Over the past few decades, genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock. However, the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnormalities, impairing meat quality and processing functionality. Early stages of animal development set the long-term growth trajectory of offspring. However, due to the seasonal reproductive cycles of ruminant livestock, gestational nutrient deficiencies caused by seasonal variations, frequent droughts, and unfavorable geological locations negatively affect fetal development and their subsequent production efficiency and meat quality. Therefore, enrolling livestock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest. These crucial early developmental stages include embryonic, fetal, and postnatal stages, which have stage-specific effects on subsequent offspring development, body composition, and meat quality. This review summarizes contemporary research in the embryonic, fetal, and neonatal development, and the impacts of maternal nutrition on the early development and programming effects on the long-term growth performance of livestock. Understanding the developmental and metabolic characteristics of skeletal muscle, adipose, and fibrotic tissues will facilitate the development of stage-specific nutritional management strategies to optimize production efficiency and meat quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Ewe nutrition during gestation, either in excess or in deficit, may influence fetal development and the postnatal life of the lamb. The objective of this study was to evaluate the effects of use the of energy (ME) and energy/protein (MECP) supplementation in the ewe's diet in the last third of gestation on maternal placental and endocrine characteristics, as well as on the behavior of neonatal lambs and productive performance. ME and MECP ewes had higher serum concentrations of triiodothyronine and cortisol on the day of lambing. However, only ME ewes had higher placental efficiency and lower total cotyledon weight. The ME and MECP diets increased birth weight at weaning and reduced the time to kneel, to try to stand, and the latency to stand of the lambs. It is concluded that overnutrition in the last third of gestation was positive for the sheep production system, with improved production rates, hormonal profile, placental characteristics and neonatal behavior. These results are valuable to society because they indicate a management strategy during the reproductive season that can be adopted by sheep producers to increase the productivity of their flocks. The objective of the study was to evaluate energy or energy/protein supplementation in the ewe diet, in the last third of gestation, on maternal placental and endocrine characteristics, as well as its effects on the behavior of neonatal lambs and productive performance until weaning. A total of 128 ewes were used, and the experimental diet was fed from 100 days gestation until lambing, with the birth of 172 lambs. The ewes were distributed into three treatments: CTL (control, n = 43) with metabolizable energy (ME) and crude protein (CP) intake according to NRC (1985); ME (energy supplementation, n = 44) plus 21% ME; and MECP (energy/protein supplementation, n = 41) plus 26% ME and CP. Body weight, body condition score, serum hormone concentrations, placental characteristics, lamb performance and behavior, and production efficiency of the ewe from lambing to weaning were measured. ME and MECP ewes were heavier before (p = 0.006) and just after lambing (p = 0.002) and had higher serum triiodothyronine (p = 0.001) and cortisol (p = 0.004) concentrations on the day of lambing. ME ewes had higher placental efficiency (p = 0.036) and lower total cotyledon weight (p = 0.011). ME and MECP diets increased both lamb birth weight (p = 0.015) and weaning weight (p = 0.009). Production efficiency at birth and at weaning was not influenced (p > 0.05) by treatments. Lamb behavior was influenced by the ME and MECP diets, reducing the time to kneel (p ≤ 0.05), to try to stand (p ≤ 0.05), and the latency to stand (p ≤ 0.005). It is concluded that overnutrition in the last third of gestation was positive for the ovine production system, with improved production rates, hormonal profile, placental characteristics, and neonatal behavior. [ABSTRACT FROM AUTHOR]

Background: Nutritional status and maternal feeding during the perinatal and postnatal periods can program the offspring to develop long-term health alterations. Epidemiologic studies have demonstrated an association between maternal obesity and intellectual disability/cognitive deficits like autism spectrum disorders (ASDs) in offspring. Experimental findings have consistently been indicating that maternal supplementation with methyl donors, attenuated the social alterations and repetitive behavior in offspring. Objective: This study aims to analyze the effect of maternal cafeteria diet and methyl donor-supplemented diets on social, anxiety-like, and repetitive behavior in male offspring, besides evaluating weight gain and food intake in both dams and male offspring. Design: C57BL/6 female mice were randomized into four dietary formulas: control Chow (CT), cafeteria (CAF), control + methyl donor (CT+M), and cafeteria + methyl donor (CAF+M) during the pre-gestational, gestational, and lactation period. Behavioral phenotyping in the offspring was performed by 2-month-old using Three-Chamber Test, Open Field Test, and Marble Burying Test. Results: We found that offspring prenatally exposed to CAF diet displayed less social interaction index when compared with subjects exposed to Chow diet (CT group). Notably, offspring exposed to CAF+M diet recovered social interaction when compared to the CAF group. Discussion: These findings suggest that maternal CAF diet is efficient in promoting reduced social interaction in murine models. In our study, we hypothesized that a maternal methyl donor supplementation could improve the behavioral alterations expected in maternal CAF diet offspring. Conclusions: The CAF diet also contributed to a social deficit and anxiety-like behavior in the offspring. On the other hand, a maternal methyl donor-supplemented CAF diet normalized the social interaction in the offspring although it led to an increase in anxiety-like behaviors. These findings suggest that a methyl donor supplementation could protect against aberrant social behavior probably targeting key genes related to neurotransmitter pathways. [ABSTRACT FROM AUTHOR]

Developmental programming is the concept that 'stressors' during development (i.e. pregnancy, the perinatal period and infancy) can cause long-term changes in gene expression, leading to altered organ structure and function. Such long-term changes are associated with an increased risk of a host of chronic pathologies, or non-communicable diseases including abnormal growth and body composition, behavioural or cognitive dysfunction, metabolic abnormalities, and cardiovascular, gastro-intestinal, immune, musculoskeletal and reproductive dysfunction. Maternal nutrition during the periconceptual period, pregnancy and postnatally can have profound influences on the developmental program. Animal models, including domestic livestock species, have been important for defining the mechanisms and consequences of developmental programming. One of the important observations is that maternal nutritional status and other maternal stressors (e.g. environmental temperature, high altitude, maternal age and breed, multiple fetuses, etc.) early in pregnancy and even periconceptually can affect not only embryonic/fetal development but also placental development. Indeed, altered placental function may underlie the effects of many maternal stressors on fetal growth and development. We suggest that future directions should focus on the consequences of developmental programming during the offspring's life course and for subsequent generations. Other important future directions include evaluating interventions, such as strategic dietary supplementation, and also determining how we can take advantage of the positive, adaptive aspects of developmental programming. Developmental programming, sometimes called fetal programming, is the concept that insults to the embryo/fetus during development can have long-term consequences throughout the lifetime of the offspring, including a host of chronic health problems. One of the most obvious and well-studied insults is poor maternal nutrition. This review discusses our current understanding of how developmental programming occurs, strategies to minimise its negative consequences (and, perhaps, take advantage of its positive consequences), as well as future directions for research. [ABSTRACT FROM AUTHOR]

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their offspring, focusing on the influence of age and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of glyphosate herbicide-based (O-GHB) and controls (O-CON) rats at 3, 6, and 12 months of age. O-GHB groups showed no changes in arterial blood pressure or aorta histological analysis. Relaxation to acetylcholine was reduced in O-GHB than O-CON. Acute TEMPOL increased relaxation to acetylcholine in O-GHB at 6 and 12 months of age. The aorta from O-GHB was hyperactive to phenylephrine only at 6 months of age. Preincubation with N-nitro- L -arginine methyl ester (L -NAME) increased contraction to phenylephrine more in O-CON than O-GHB. TEMPOL similarly reduced phenylephrine response. This effect was prevented by L -NAME. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that although no changes in cardiac or histological parameters have been demonstrated, the current levels considered safe for exposure to glyphosate deserve further investigation, especially during pregnancy. [ABSTRACT FROM AUTHOR]

Oxidative stress arises when the generation of reactive oxygen species or reactive nitrogen species overwhelms antioxidant systems. Developing kidneys are vulnerable to oxidative stress, resulting in adult kidney disease. Oxidative stress in fetuses and neonates can be evaluated by assessing various biomarkers. Using animal models, our knowledge of oxidative-stress-related renal programming, the molecular mechanisms underlying renal programming, and preventive interventions to avert kidney disease has grown enormously. This comprehensive review provides an overview of the impact of perinatal oxidative stress on renal programming, the implications of antioxidant strategies on the prevention of kidney disease, and the gap between animal models and clinical reality. [ABSTRACT FROM AUTHOR]

Environmental effects on gene expression and offspring development can be mediated by epigenetic modifications. It is well established that maternal diet influences DNA methylation patterns and phenotypes in the offspring; however, the epigenetic effects of paternal diet on developing offspring warrants further investigation. Here, we examined how a prepubertal methionine-enriched paternal diet affected sperm DNA methylation and its subsequent effects on embryo gene expression. Three treatment and three control rams were bred to seven ewes, and blastocysts were flushed for RNA extraction. Semen was collected from all rams and submitted for reduced representation bisulfite sequencing analysis. In total, 166 differentially methylated cytosines were identified in the sperm from treatment versus control rams. Nine genes were found to be differentially expressed in embryos produced from treatment versus control rams, and seven differentially methylated cytosines in the sperm were found to be highly correlated with gene expression in the embryos. Our results demonstrate that sperm methylation differences induced by diet may influence fetal programming. [ABSTRACT FROM AUTHOR]

Nutritional restriction during developmental periods impairs organ physiology. Female rats were subjected to protein restriction during pregnancy and lactation to analyze dental and maxillary development. Four exposure groups were considered: normal‐protein diet during pregnancy and lactation (NP, 17% casein), low‐protein diet during lactation (LP‐L, 6% casein), low‐protein diet during pregnancy and lactation (LP), and low‐protein diet during pregnancy (LP‐G). Maxillae from 15‐day‐old male pups were collected. All protein‐restricted groups presented increased dentin thickness and reduced alveolar bone area. When protein restriction was applied during both gestation and lactation (LP), harmful effects were observed in the form of loss of protective OPG (osteoprotegerin) in tooth epithelium‐mesenchyme, due to higher RANKL expression, delay in odontoblast maturation, less dental pulp vascularity, reduction in amount of alveolar bone, and less matrix mineralization. In the LP‐L group, effects of protein restriction seemed less harmful, and despite less alveolar bone, the enhancement in BMP‐7, VEGF, and RANKL seems a compensatory signal to maintain maxillary osteogenesis. In LP‐G animals, Dspp expression was higher, suggesting a delay in odontoblast maturation or expression recuperation. In conclusion, maternal protein restriction affects dental and maxillary development. A low‐protein diet only in gestation allows for normal development. A low‐protein diet during gestation‐lactation results in impaired odontogenesis that may increase susceptibility of dental anomalies. [ABSTRACT FROM AUTHOR]

Altered fetal growth, which can occur due to environmental stressors during pregnancy, may program a susceptibility to metabolic disease. Gestational exposure to the air pollutant ozone is associated with fetal growth restriction in humans and rodents. However, the impact of this early life ozone exposure on offspring metabolic risk has not yet been investigated. In this study, fetal growth restriction was induced by maternal inhalation of 0.8 ppm ozone on gestation days 5 and 6 (4 hr/day) in Long Evans rats. To uncover any metabolic inflexibility, or an impaired ability to respond to a high‐fat diet (HFD), a subset of peri‐adolescent male and female offspring from filtered air or ozone exposed dams were fed HFD (45% kcal from fat) for 3 days. By 6 weeks of age, male and female offspring from ozone‐exposed dams were heavier than offspring from air controls. Furthermore, offspring from ozone‐exposed dams had greater daily caloric consumption and reduced metabolic rate when fed HFD. In addition to energy imbalance, HFD‐fed male offspring from ozone‐exposed dams had dyslipidemia and increased adiposity, which was not evident in females. HFD consumption in males resulted in the activation of the protective 5'AMP‐activated protein kinase (AMPKα) and sirtuin 1 (SIRT1) pathways in the liver, regardless of maternal exposure. Unlike males, ozone‐exposed female offspring failed to activate these pathways, retaining hepatic triglycerides following HFD consumption that resulted in increased inflammatory gene expression and reduced insulin signaling genes. Taken together, maternal ozone exposure in early pregnancy programs impaired metabolic flexibility in offspring, which may increase susceptibility to obesity in males and hepatic dysfunction in females. [ABSTRACT FROM AUTHOR]

The worldwide epidemic of obesity is associated with numerous comorbid conditions, including metabolic diseases such as insulin resistance and diabetes, in particular. The situation is likely to worsen, as the increase in obesity rates among children will probably lead to an earlier onset and more severe course for metabolic diseases. The origin of this earlier development of obesity may lie in both behavior (changes in nutrition, physical activity, etc.) and in children's history, as it appears to be at least partly programmed by the fetal/neonatal environment. The concept of the developmental origin of health and diseases (DOHaD), involving both organogenesis and epigenetic mechanisms, encompasses such programming. Epigenetic mechanisms include the action of microRNAs, which seem to play an important role in adipocyte functions. Interestingly, microRNAs seem to play a particular role in propagating local insulin resistance to other key organs, thereby inducing global insulin resistance and type 2 diabetes. This propagation involves the active secretion of exosomes containing microRNAs by adipocytes and adipose tissue-resident macrophages, as well as long-distance communication targeting the muscles and liver, for example. Circulating microRNAs may also be useful as biomarkers for the identification of populations at risk of subsequently developing obesity and metabolic diseases. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of gestational supplementation strategy on nitrogen isotopic signature in blood plasma of beef cows and their progeny. The study comprised 15 pregnant Nellore cows divided into three different supplementation protocols: NP) non-programmed group; PP) cows receiving protein–energy supplement in the last third of pregnancy; and FP) cows receiving protein–energy supplement throughout the gestational period. Blood plasma from cows was sampled at the beginning of gestation, in the prepartum, and postpartum periods as well as from their calves at 30 and 180 days of age, for the analysis of stable isotope ratios 15 N/14 N. At pre- and postpartum periods, cows fed PP and FP presented greater abundance of δ15 N compared to NP (p < 0.05) at pre- and postpartum. All three groups showed significant differences (p < 0.05) in the postpartum period. The δ15 N values of calves at 30 days of age differed between the NP group and PP and FP groups (p < 0.05), with no difference (p > 0.05) at 180 days of age. The different gestational supplementation strategies influenced isotopic fractionation of nutrients of cows and their calves after birth, indicating effects on nutritional metabolism and cumulative behavior on isotope abundance related to consumption during gestation. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine–metabolic disorder of unknown etiology. Hyperandrogenism (HA) is the main diagnostic criteria for PCOS, in addition to being a risk factor for developing several disorders throughout the patient's life, including pregnancy. However, the impact on offspring is little known. Therefore, the aim of this work was to evaluate the effect of maternal HA on glucose metabolism and hepatic lipid accumulation in adult offspring. We used Balb/c mice treated with dehydroepiandrosterone (DHEA) for 20 consecutive days. The ovary of DHEA-treated mice showed hemorrhagic bodies, an increased number of atretic follicles, and greater expression of genes related to meiotic cell cycle and DNA repair. The DHEA offspring (O-DHEA) had low birth weight, and some pups showed malformations. However, O-DHEA individuals gained weight rapidly, and the differences between them and the control group became significantly greater in adulthood. Moreover, O-DHEA presented higher serum glucose after a 6 h fast and a larger area under glucose, insulin, and pyruvate tolerance test curves. Oil Red O staining showed a more significant accumulation of fat in the liver but no changes in serum cholesterol and triacylglycerol levels. In summary, our results show that HA, induced by DHEA, affects gene expression in oocyte, which in turn generates defects in embryonic development, insulin resistance, and alteration in hepatic gluconeogenesis and lipid metabolism in O-DHEA, thereby increasing the risk of developing metabolic diseases. [ABSTRACT FROM AUTHOR]

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here, we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, altered glucose tolerance, and coagulopathy; whereas male F1 offspring exhibited altered glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity (indicative of macrophage presence) and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in the offspring, and that the effects of inflammation may cross generations. Our findings provide evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Autism spectrum disorder (ASD) is considered a significant behavioral problem that is characterized by impairment in social interaction and communication. It is believed that some cases of ASD originate in the intrauterine maternal environment. Therefore, we hypothesized that there might be qualitative changes in the interaction between the mother and fetus in ASD during the prenatal period, hence, we investigated the similarity patterns between maternal and fetal heart rate (HR). Methods: In this study, we first demonstrate the presence and formation of similarities between maternal and fetal RR interval (RRI) collected from typical developmental mice at different embryonic days (EDs), ED13.5, ED15.5, ED17.5, and ED18.5. The similarities were quantified by means of cross-correlation (CC) and magnitude-squared coherence (MSC) analyses. Correlation analysis between the CC coefficients and EDs and between MSC coefficients and EDs showed that the same coefficients increase with EDs, suggesting that similarities between maternal and fetal RRI are associated with typical fetal development. Next, because maternal and fetal similarities were indicative of development, a comparison analysis between the autism mouse model (injected with valproic acid (VPA)), and the control group (injected with saline) was performed for ED15.5 and ED18.5. Results: The results of the comparison showed that the CC and MSC coefficients of VPA fetuses were significantly lower than that of the control group. The lower coefficients in VPA-treated mice suggest that they could beone of the features of ASD symptoms. The findings of this study can assist in identifying potential ASD causes during the prenatal period. [ABSTRACT FROM AUTHOR]

Research on maternal-fetal epigenetic programming argues that adverse exposures to the intrauterine environment can have long-term effects on adult morbidity and mortality. However, causal research on epigenetic programming in humans at a population level is rare and is often unable to separate intrauterine effects from conditions in the postnatal period that may continue to impact child development. In this study, we used a quasi-natural experiment that leverages state-year variation in economic shocks during the Great Depression to examine the causal effect of environmental exposures in early life on late-life accelerated epigenetic aging for 832 participants in the US Health and Retirement Study (HRS). HRS is the first population-representative study to collect epigenome-wide DNA methylation data that has the sample size and geographic variation necessary to exploit quasi-random variation in state environments, which expands possibilities for causal research in epigenetics. Our findings suggest that exposure to changing economic conditions in the 1930s had lasting impacts on next-generation epigenetic aging signatures that were developed to predict mortality risk (GrimAge) and physiological decline (DunedinPoAm). We show that these effects are localized to the in utero period specifically as opposed to the preconception, postnatal, childhood, or early adolescent periods. After evaluating endogenous shifts in mortality and fertility related to Depression-era birth cohorts, we conclude that these effects likely represent lower bound estimates of the true impacts of the economic shock on long-term epigenetic aging. [ABSTRACT FROM AUTHOR]

Objective: Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year. Methods: We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included. Results: A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0–4 months vs. > 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown. Conclusion: Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children. [ABSTRACT FROM AUTHOR]

Maternal overnutrition during pregnancy leads to metabolic and immune alterations, including obesity, hyperphagia, and central and peripheral inflammation in offspring. Exposure to high-energy diets during pregnancy primes ghrelin sensitivity to overfeeding in the offspring at early stages of life. Overfeeding has also been partially related to the early stages of chronic stress. We hypothesized that maternal programming sensitizes ghrelin-induced overfeeding following a chronic stress schedule in the offspring. We used a nutritional programming model exposing female Wistar rats to a cafeteria (CAF) or control diet from prepregnancy to weaning. Male offspring were injected with ghrelin and then subjected to a chronic immobilization stress (CIS) schedule, after which food intake was determined. Hypothalamic and plasma accumulation of cytokines and cortisol were evaluated using BioPlex analysis and enzyme-linked immunosorbent assay, respectively. We found that rats exposed to the CAF diet exhibited overfeeding after fasting and peripheral ghrelin administration, which was exacerbated in rats exposed to chronic stress. Offspring exposed to the CAF diet accumulated pro-inflammatory interleukin-6 (IL-6), interferon-γ, and monocyte chemoattractant protein-1 cytokines in plasma, and IL-6 cytokine in the hypothalamus. Ghrelin-sensitive overfeeding in rats exposed to CAF diet + CIS display increased cortisol levels and decreased IL-6 accumulation in plasma. Together, our results suggest that maternal nutritional programming primes susceptibility to ghrelin response for overfeeding after a CIS schedule that mirrors plasma cortisol accumulation in male offspring. [Display omitted] Exposure to high-energy diets during pregnancy primes ghrelin sensitivity to palatable cafeteria diet overfeeding in male offspring. Chronic immobilization stress sensitizes ghrelin-induced overfeeding of palatable cafeteria diet in male offspring. [ABSTRACT FROM AUTHOR]

The role of folate, in its synthetic and bioactive form, as an in utero modifier of metabolic outcomes in mothers and offspring is examined in this review. During pregnancy, a continuum of adaptive changes occurs to support maternal and fetal requirements. However, an unfavorable in utero environment may lead to permanent changes in cellular and physiological functions, adversely affecting the development of the child and postpartum health of the mother. In North American countries, synthetic folic acid (FA) is overconsumed by pregnant women, and uncertainty exists about its potential unintended health effects. Because the metabolism of FA is different than that of other folate forms, it may modulate disease risk differently. The bioactive form of folate, 5-methyltetrahydrofolic acid, has emerged as a popular alternative to FA, but clinical studies comparing their effects during pregnancy are limited. Current evidence points to the need for caution when maternal intake of either folate form exceed recommended amounts. Research directed toward defining an optimal folate dose and form for healthy pregnancy and long-term metabolic outcomes in mothers and children is urgently needed. [ABSTRACT FROM AUTHOR]

Seventy-two non-lactating, pregnant Angus cows (initial body weight (BW) = 637 ± 13 kg; body condition score (BCS) = 5.5 ± 0.07 yr; and age = 6.1 ± 0.57; exposed to AI = 54 and Bull = 18) were ranked by pregnancy type, BW, and BCS and assigned to receive a supplement containing: 1) Cu, Mn, and Zn sulfate source (INR; n = 24), or 2) Cu, Mn, and Zn organic-complexed source (ORG; n = 24), or 3) Cu, Mn, and Zn hydroxychloride source (HDX; n = 24). From d -11 (d of gestation 195 ± 5.1) to calving, cows were allocated to rangeland pasture. From d 0 until calving, cows were gathered and fed the treatments thrice a week. Cow BW and BCS were recorded, and blood was collected on d -11 and -10, upon calving, and at weaning. Liver biopsies were performed in all cows on d -10 and upon calving (cows and calves). Longissimus muscle (LM) biopsies were performed, and blood was collected in all calves upon calving. Calves were weaned on d 260, backgrounded for 99 d, and then sent to a commercial feedyard. Calves blood samples were collected on days 245, 260, 264, 268, 275, 280, and 288. No differences were detected (P ≥ 0.31) for cow BW and BCS changes among treatments during gestation, and mineral sources did not improve (P ≥ 0.16) mineral liver concentrations of Zn, Mn, Se, and Co at parturition. However, there was a tendency (P = 0.07) for HDX to have improved liver Cu concentration vs. ORG and INR cows. Cows fed HDX and ORG had improved (P ≤ 0.03) BCS at weaning, and BCS changed from parturition to weaning vs. INR cows. No treatment differences were detected (P ≥ 0.21) for calf birth measurements, IgG levels, mRNA expression of hepatic enzymes, or LM genes associated with muscle and adipose tissue development. At weaning and during the backgrounding, no treatment differences were detected (P ≥ 0.21) for offspring performance, health outcomes, plasma cortisol, serum nonesterified fatty acids (NEFA), and serum beta-hydroxybutyrate (BHBA). However, a tendency for a treatment × d interaction was detected (P = 0.07) for haptoglobin concentrations, which was reduced (P < 0.01) in calves from cows supplemented with HDX vs. calves from cows supplemented with ORG and INR 15 d after weaning. No treatment effects were noted (P ≥ 0.35) for final BW, feedyard ADG, and carcass traits between treatment groups. Overall, different sources of Cu, Mn, and Zn supplemented to late-gestating beef cows yielded similar cow-calf productive responses from birth to finishing., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In tropical beef cattle production systems, animals are commonly raised on pastures, exposing them to potential stressors. The end of gestation typically overlaps with a dry period characterized by limited food availability. Late gestation is pivotal for fetal development, making it an ideal scenario for inter- and transgenerational effects of the maternal gestational environment. Intergenerational effects occur due to exposure during gestation, impacting the development of the embryo and its future germline. Transgenerational effects, however, extend beyond direct exposure to the subsequent generations. The objective of the present study was to verify these effects on the post-natal performance of zebu beef cattle. We extended the use of a reaction norm model to identify genetic variation in the animals' responses to transgenerational effects. The inter- and transgenerational effects were predominantly positive (-0.09% to 19.74%) for growth and reproductive traits, indicating improved animal performance on the phenotypic scale in more favourable maternal gestational environments. Additionally, these effects were more pronounced in the reproductive performance of females. On average, the ratio of direct additive genetic variances of the slope and intercept of the reaction norm ranged from 1.23% to 3.60% for direct and from 10.17% to 11.42% for maternal effects. Despite its relatively modest magnitude, this variation proved sufficient to prompt modifications in parameter estimates. The average percentage variation of direct heritability estimates ranged from 19.3% for scrotal circumference to 33.2% for yearling weight across the environmental descriptors evaluated. Genetic correlations between distant environments for the studied traits were generally high for direct effects and far from unity for maternal effects. Changes in EBV rankings of sires across different gestational environments were also observed. Due to the multifaceted nature of inter- and transgenerational effects of the maternal gestational environment on various traits of beef cattle raised under tropical pasture conditions, they should not be overlooked by producers and breeders. There were differences in the specific response of beef cattle to variations in the quality of the maternal gestational environment, which can be partially explained by transgenerational epigenetic inheritance. Adopting a reaction norm model to capture a portion of the additive variance induced by inter- or transgenerational effects could be an alternative for future research and animal genetic evaluations., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Growing evidence suggests intergenerational effects of paternal pre-conceptional smoking through the germ line, but its specific impact on offspring semen quality remains uncertain because of challenges in isolating paternal exposure from maternal passive smoking or underreporting., Methods: We reran previous analyses estimating differences in semen parameters and testicular size according to paternal smoking in 867 young adult men, adding first-trimester maternal plasma cotinine to the original adjustment for maternal self-reported smoking. We also estimated differences in sperm DNA fragmentation. Paternal smoking was reported by the pregnant women around gestational week 16. Analyses were additionally adjusted for household occupational status, parental ages at birth, maternal pre-pregnancy body mass index and alcohol consumption, and abstinence time, and accounted for spillage, minutes from ejaculation to analysis, and son's own smoking., Results: We found no association between paternal preconceptional smoking and any of the semen parameters or testicular size. Adjustment for son's own smoking did not change results., Discussion: While maternal plasma cotinine offers an objective measure of tobacco exposure and allows for a more thorough adjustment of maternal smoking, the high correlation between paternal pre-conceptional smoking and maternal cotinine exposure may, have resulted in overadjustment removing some paternal effect. Inability to distinguish between paternal never smokers and former smokers, may have led to misclassification of paternal pre-conceptional smoking and underestimation of associations., Conclusion: We found no support for an independent association between paternal pre-conceptional smoking and semen quality in young adult sons, but studies with more detailed paternal smoking history are needed before firm conclusions can be drawn., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: The term "fetal programming" refers to the effects of endogenous and exogenous corticosteroids, whether received from the mother or the fetus, on brain development and the hypothalamic-pituitary-adrenal axis reset. The authors of this narrative review examine the WHO's guidelines for prenatal corticosteroids in pregnant women who are at high risk of premature delivery. These guidelines are regarded as the best available for preventing late-life problems resulting from preterm., Methods: In order to find full-text publications published in peer-reviewed journals between 1990 and 2023 that were written in English, the authors searched PubMed, Scopus, Cochrane Library, and Web of Science., Results: The authors highlight the possible adverse long-term effects of prenatal corticosteroid medication on human brain development and function. This pharmacological feature is therapeutically significant because there is less evidence in the scientific literature regarding the potential role that the timing, mode, and dosage of exogenous steroid treatment may have in neurological illnesses down the road., Conclusions: The authors expect that these studies will shed light on the relationship between specially designed prenatal corticosteroid therapy and the molecular mechanisms underlying the prenatal programming of neurodevelopment in childhood and adulthood.

Background: Maternal obesity and excessive weight gain during pregnancy are associated with higher birth weight and increased risk of childhood obesity., Objective: This study investigated the effect of a high-protein and low-glycaemic-index (HPLGI) diet during pregnancy on offspring body composition and metabolic health., Methods: We conducted a dietary intervention study in pregnant women with a pre-pregnancy BMI of 28-45 kg/m 2 who were randomly assigned to an HPLGI diet or a moderate-protein moderate-glycaemic-index (MPMGI) diet. A total of 208 offspring born to these women were followed-up from birth to 5 years of age., Results: No differences were found on BMI z-scores at different ages; however, offspring born to women on the HPLGI diet exhibited 0.43 mmol/L higher glucose levels (p = 0.017) at birth compared with the MPMGI diet. At 3 years of age, HPLGI offspring had 0.09 mmol/L lower levels of HDL-cholesterol (p = 0.018) and 16% higher levels of triglycerides (p = 0.044). At 5 years of age, they had 0.25 mmol/L higher total cholesterol levels (p = 0.027) and 0.27 mmol/L higher LDL-cholesterol levels (p = 0.003) compared with the MPMGI diet., Conclusion: An HPLGI diet during pregnancy may lead to adverse metabolic outcomes in the offspring, necessitating further investigation into long-term health implications., (© 2024 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

This review summarizes recent findings on stress-related programming of brain development in utero , with an emphasis on situating findings within the mothers' broader psychosocial experiences. Meta-analyses of observational studies on prenatal stress exposure indicate the direction and size of effects on child neurodevelopment are heterogeneous across studies. Inspired by lifespan and topological frameworks of adversity, we conceptualize individual variation in mothers' lived experience during and prior to pregnancy as a key determinant of these heterogeneous effects across populations. We structure our review to discuss experiential categories that may uniquely shape the psychological and biological influence of stress on pregnant mothers and their developing children, including current socioeconomic resources, exposure to chronic and traumatic stressors, culture and historical trauma, and the contours of prenatal stress itself. We conclude by identifying next steps that hold potential to meaningfully advance the field of fetal programming.

Fetal growth restriction (FGR) is a risk factor for obesity in adult life. Importantly, growth-restricted females are more prone to obesity than males. The mechanisms involved in this sexually dimorphic programming are not known. Previously, we have demonstrated that ambient hyperthermia (40°C) led to placental insufficiency and significant FGR, and the perirenal adipose tissue undergoes sexually dimorphic gene expression. We demonstrated that males undergo significant changes in gene expression with growth restriction. This was not the case in females. We have also demonstrated that the isolated preadipocytes from male FGR (MFGR) have reduced differentiation potential compared to control males & females and female FGR (FFGR). Thus, we hypothesized that growth restriction differentially programs gene expression and genetic pathways in perirenal preadipocytes, which reduces their differentiation potential in male fetuses in a sexually dimorphic manner. We created FGR by exposing pregnant sheep to ambient hyperthermia. After isolating preadipocytes from perirenal adipose tissue, we differentiated them following published protocols. We examined the gene expression before and after differentiation from control male, control female, MFGR, and FFGR female. We also compared our data with other published studies in mouse and human preadipocytes. Our results demonstrate that a set of 21 genes altered with preadipocyte differentiation to mature adipocytes is common in adipose tissue from both sexes, humans, mice, and sheep, at different organismal ages (embryonic, fetal, and adult) and different sites (subcutaneous inguinal, pancreatic, perirenal). We also demonstrate that female FFGR fetuses demonstrate all these 21 genes altered similar to control males and females; however, MFGR fetuses have six genes (Dgat2, Fabp4, Lipe, Lrrfip1, Spred3, and Thrsp) that are not changed with preadipocyte differentiation to mature adipocyte. These genes may be responsible for reduced differentiation potential and obesity in FGR males compared to FGR females. Another important finding of the present study is that Lrrfip1, known to be associated with obesity, was upregulated with FGR and requires further investigation. Overall, our studies provide several target genes that may play a crucial role in reducing the risk of MFGR for obesity., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

The performance of an adult dairy cow may be influenced by heat stress that occurs during her gestation. The present study investigated potential effects of temperature-humidity index (THI) experienced by a cow during pregnancy on the gestated daughter's performance on her first lactation, for the French Holstein and Montbéliarde dairy cattle populations. We analyzed 14 traits, all measured on genotyped cows: 305-d milk, fat, and protein yields; 305-d SCS; clinical mastitis (both occurrence and number of events); body conformation traits; and heifer and cow conception rate. To study the effect of heat stress, we considered the THI experienced by the gestating cow, averaged for each month of her pregnancy and then categorized in 7 classes (≤40, [40,45], [45,50], [50,55], [55,60], [60,65], and >65). These average THI classes were then fitted as categorical covariates in the regression models used for this study, which included other fixed effects, and the GEBV as a covariate, both specific to each trait, the latter being previously obtained from the official French evaluations. The THI effect was therefore estimated as the deviation between the observed and predicted performances. In general, the estimated heat stress effects were small, presenting limited practical impact on the studied traits, and particularly for fertility and udder health, the estimated heat stress effects were not statistically significant. For the production traits (i.e., milk, fat, and protein yields), the estimated effect associated with high THI experienced at the beginning of the gestation was negative, and slightly positive when associated with high THI experienced by the dam at the end of her pregnancy. Finally, our results suggest that under the current French climate conditions, heat stress experienced by cows during any stage of their pregnancy has limited impact on the future performance of their gestated daughters; however, we cannot exclude that a significant in utero heat stress effect may be present in climate conditions warmer than the French., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

A prenatal low-protein (LP) diet disrupts glucose homeostasis in adult offspring. Skeletal muscles are one of the main sites of glucose clearance, and mitochondria residing in the muscle fibers are central to glucose homeostasis. Our previous studies indicated that impaired mitochondrial health is central to dysregulated glucose metabolism in the gastrocnemius muscle of the LP-programmed female rats. In addition, dysfunctional mitochondria are often an indicator of underlying irregularities in energy metabolism and metabolic inflexibility. Therefore, this study examined the mitochondrial function and metabolic flexibility in the skeletal muscles of prenatal LP-programmed adult male rats. Pregnant Wistar rats were randomly allotted to a control diet (20% protein) or an isocaloric LP diet (6% protein). Standard laboratory rat chow was given to the dams and the pups after delivery and weaning. Gene and protein expressions, mtDNA copy number, and electron microscopy were assessed in gastrocnemius (GS) muscle, and the mitochondrial oxygen consumption rate was determined using isolated flexor digitorum brevis muscle fibers. The genes associated with mitochondrial outer membrane fusion, mitofusin1 and 2 (Mfn1 and Mfn2), fission (Fis1), and biogenesis (Pgc1B, Nrf1, and Esrra) were lower in the LP group. Further, our functional studies showed that the ATP-linked oxygen consumption rate (OCR), maximal, spare respiratory, and non-mitochondrial respiration-associated OCRs were lower in the LP rats. Further, the mRNA and protein expressions of Ndufb8, a key factor involved in the complex-I catalytic activity, were downregulated in the LP group. In addition, the expression of genes linked to mitochondrial pyruvate transport (Mpc1) and metabolism (Pdha1) was lower in the LP group. In contrast, the expression of mitochondrial fatty acid transporters (Cpt1a and Cpt2) was higher in the LP when compared to the control group. However, electron microscopic analysis exhibited no difference in the mitochondrial ultrastructure in the LP muscle compared to the control. Altogether, our results indicate that the LP diet affects the mitochondrial complex-I integrity and dynamics and leads to altered expression of genes associated with substrate oxidation and mitochondrial dysfunction in the skeletal muscle of the male LP offspring.

Background/Objectives : Childhood obesity is a global health problem that affects at least 41 million children under the age of five. Increased BMI in children is associated with serious long-term health consequences, such as type 2 diabetes, cardiovascular disease, and psychological problems, including depression and low self-esteem. Although the etiology of obesity is complex, research suggests that the diet and lifestyle of pregnant women play a key role in shaping metabolic and epigenetic changes that can increase the risk of obesity in their children. Excessive gestational weight gain, unhealthy dietary patterns (including the Western diet), and pregnancy complications (such as gestational diabetes) are some of the modifiable factors that contribute to childhood obesity. The purpose of this narrative review is to summarize the most important and recent information on the impact of the diet and lifestyle of pregnant women on the risk of childhood obesity. Methods : This article is a narrative review that aims to summarize the available literature on the impact of pregnant women's diet and lifestyle on the risk of obesity in their offspring, with a focus on metabolic and epigenetic mechanisms. Results / Conclusions : Current evidence suggests that a pregnant woman's lifestyle and diet can significantly contribute to lowering the risk of obesity in their offspring. However, further high-quality research is needed to understand better the metabolic and epigenetic relationships concerning maternal factors that predispose offspring to obesity.

Introduction: Maternal diabetes increases the risk of adverse maternal, perinatal and offspring outcomes. This study aimed to address whether alterations in uterine decidualization are programmed in the prepubertal offspring from diabetic rats fed diets enriched or not in extra virgin olive oil (EVOO)., Methods: Control and mild pregestational diabetic female rats (F0) were mated with control males and fed diets enriched or not with 6 % EVOO during pregnancy. Offspring (F1) were evaluated on postnatal day 30, after induction of uterine decidualization (PMSG 50 IU- hCG 50 IU). Signaling pathways involved in decidualization, including prolactin, PPAR and mTOR pathways as well as microRNAs (miRs) regulating these pathways were evaluated by Western blot or qPCR in the decidualized uteri., Results: The offspring from diabetic rats evidenced reduced prolactin and prolactin receptor levels in the decidualized uteri. Additionally, these tissues showed increased PPARγ levels and reduced levels of its negative regulators miR-19b and miR-155. MiR-21, a microRNA that targets both PPARα and mTOR pathway regulators was reduced, whereas PPARα, PTEN and FOXO1 mRNA levels were increased in the decidualized uteri of the offspring from diabetic rats. The mTOR pathway activity was reduced in the decidualized uteri of the offspring from diabetic rats. Most of the observed alterations were prevented by the EVOO-enriched maternal diet., Discussion: Impaired pathways relevant to decidualization are programmed in the uteri of prepubertal offspring from diabetic dams, alterations capable of being prevented by maternal diets enriched in EVOO., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Extending the voluntary waiting period (VWP) for insemination in dairy cows is of interest as a strategy to reduce the frequency of calving events and inseminate at a moment with fewer fertility problems. Little is known about the calves born from dams with a different VWP followed by a different calving interval (CInt). The objective of the current study was to identify the effect of dam's CInt on body condition, metabolic status, and milk production of their offspring from birth until 100 DIM of the offspring's first lactation. Holstein-Friesian dairy cows (n = 154, 41 primiparous, 113 multiparous) were blocked according to parity, milk yield, and SCC and randomly assigned to a VWP of 50, 125, or 200 d. Female calves (n = 62) from cows with different CInt were monitored from birth until their first calving event as heifer. Certain dams were not successfully inseminated soon after the planned VWP, resulting in differences between the intended VWP and the actual CInt. Calves were regrouped according to their dam's actual CInt (CInt&#95;1: 324-408 d; CInt&#95;2: 409-468 d; CInt&#95;3: 469-586 d). The dam's CInt did not affect calf birth weight. From birth to weaning, the calves born to dams in CInt&#95;1 had a higher plasma nonesterified fatty acids (NEFA) concentration (0.34 mmol/L; CI: 0.30, 0.37) than CInt&#95;2 (0.28 mmol/L; CI: 0.26, 0.31) and CInt&#95;3 (0.26 mmol/L; CI: 0.24, 0.29) calves. Calves born to dams with a shorter CInt (CInt&#95;1) had greater IgG and IgM against keyhole limpet hemocyanin (KLH) than CInt&#95;3 (IgG: 6.05 ± 0.30 vs. 4.64 ± 0.30; IgM: 6.45 ± 0.17 vs. 5.89 ± 0.16, respectively; mean ± SE) before weaning. After weaning till calving, CInt&#95;1 calves tended to have greater plasma NEFA concentration than CInt&#95;3-calves. During the first 100 DIM, a longer CInt of the dams resulted in lower plasma IGF&#95;1 (CInt&#95;2), lower milk lactose (CInt&#95;3), and lower fat- and protein-corrected milk (FPCM; CInt&#95;2) in offspring, compared with shorter CInt of the dams (CInt&#95;1). Collectively, a longer CInt in dams did not affect birth weight of their calves or BW during the weaning or rearing phase. From birth till weaning, a longer CInt in dams resulted in less anti-KLH IgG and lower plasma NEFA concentration in plasma of the calves. During the first lactation of their offspring, a longer CInt in dams can result in a lower plasma IGF&#95;1 and FPCM during the first 100 DIM, although effects were not present in all CInt categories., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This study aimed to assess the impact of protein supplementation and its interaction with calf sex (CS) on the performance, metabolism and physiology of pregnant beef cows. Fifty-two multiparous Zebu beef cows carrying female (n = 22) and male (n = 30) fetuses were used. Cows were individually housed from day 100 to 200 of gestation and randomly assigned to restricted (RES, n = 26) or supplemented (SUP, n = 26) groups. The RES cows were ad libitum fed a basal diet (corn silage + sugarcane bagasse + mineral mixture), achieving 5.5% crude protein (CP), while SUP cows received the same basal diet plus a protein supplement (40% CP, at 3.5 g/kg of body weight). All cows were fed the same diet during late gestation. Differences were declared at p < 0.05. No significant interaction between maternal nutrition and calf sex was found for maternal outcomes (p ≥ 0.34). The SUP treatment increased the total dry matter (DM) intake (p ≤ 0.01) by 32% and 19% at mid- and late-gestation respectively. The total tract digestibility of all diet components was improved by SUP treatment at day 200 of gestation (p ≤ 0.02), as well as the ruminal microbial CP production (p ≤ 0.01). The SUP treatment increased (p ≤ 0.03) the cows' body score condition, ribeye area, the average daily gain (ADG) of pregnant components (PREG; i.e., weight accretion of cows caused by pregnancy) and the ADG of maternal tissues (i.e., weight accretion discounting the gain related to gestation) in the mid-gestation. The SUP cows exhibited a lower maternal ADG (p < 0.01) compared to RES cows in late pregnancy. There was a 24% additional gain (p < 0.01) in the PREG components for SUP cows during late gestation, which in turn improved the calf birthweight (p = 0.05). The uterine arterial resistance and pulsatility indexes (p ≤ 0.01) at mid-gestation were greater for RES cows. In conclusion, protein supplementation during mid-gestation is an effective practice for improving maternal performance, growth of the gravid uterus and the offspring's birth weight., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Hormonal imbalance during pregnancy is a risk factor for neuropsychiatric impairment in the offspring. It has been suggested that hypothyroidism leads to dysfunction of cortical GABAergic interneurons and inhibitory system development that in turn underlies impairment of the central nervous system. Here we investigated how gestational hypothyroidism affected offspring GABAergic system development as well as redox regulation parameters, because of previous links identified between the two. Experimental Gestational Hypothyroidism (EGH) was induced in CD-1 mice with 0.02% methimazole (MMI) in drinking water from embryonic day 9 (E9) until tissue collection at embryonic day 14 (E14) or E18. We examined GABAergic cell distribution and inhibitory system development gene expression as well as redox relevant gene expression and direct measures across all embryos regardless of sex. Intrauterine restriction of maternal thyroid hormones significantly impacted both of these outcomes in brain, as well as altering redox regulation in the placenta. GAD67+ neuronal migration was reduced, accompanied by a disruption in gene expression influencing GABAergic cell migration and cortical inhibitory neural system development. EGH also altered embryonic brain gene expression of Gpx1, Nfe2l2, Cat levels in the dorsal E14 brains. Additionally, EGH resulted in elevated TBARS, Gpx1 and Nfe2l2 in the ventral E18 brains. Furthermore, EGH downregulated placental Gpx1 gene expression at E14 and increased protein oxidation at E18. These findings support the hypothesis that sufficient maternal thyroid hormone supply to the fetus influences central nervous system development, including processes of GABAergic system development and redox equilibrium., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear., Aim: The present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring., Methods: Dams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography., Results: Serum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blot analysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes.

Purpose: There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life., Methods: Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20 years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons., Results: There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18), P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1)., Conclusion: The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)