(-)-Epicatechin treatment modify the expression of genes related to atrophy in gastrocnemius muscle of male rats obese by programing.

The aim of this study is to determine if the offspring of mothers with obesity, present disorders in the expression of genes related to atrophy or protein synthesis in the muscle and if these disorders are modified with the (-)-epicatechin (Epi) treatment. Six male offspring per group were randomly assigned to the control groups [C and offspring of maternal obesity (MO)] or the Epi intervention groups, Epi treatment for 13 weeks (C + Epi long or MO + Epi long), or Epi administration for two weeks (C + Epi short or MO + Epi short). The effect of Epi in the gastrocnemius tissue was evaluated, analyzing mRNA and protein levels of Murf1, MAFbx, Foxo1, NFkB, and p70S6K-alpha. After the analysis by two-way ANOVA, we found an influence of the Epi long treatment over the model, by decreasing the Murf1 gene expression in both groups treated with the flavonoid (C + Epi long and MO + Epi long) (p = 0.036). Besides, Epi long treatment over the NFκB expression, by decreasing the fold increase in both groups treated with the flavonoid (C + Epi long and MO + Epi long) (p = 0.038). We not find any interaction between the variables or changes in the MAFbx, Foxo1 mRNA, neither in the phosphorylated/total protein ratio of NFκB, Foxo1, or p70S6K-alpha. In conclusions, treatment with a long protocol of Epi, reduces the mRNA of the muscle atrophy genes Murf 1 and NFkB, in the gastrocnemius muscle; however, these changes are not maintained at protein level.

Contribution of the seminal microbiome to paternal programming.

The field of Developmental Origins of Health and Disease has primarily focused on maternal programming of offspring health. However, emerging evidence suggests that paternal factors, including the seminal microbiome, could potentially play important roles in shaping the developmental trajectory and long-term offspring health outcomes. Historically, the microbes present in the semen were regarded as inherently pathogenic agents. However, this dogma has recently been challenged by the discovery of a diverse commensal microbial community within the semen of healthy males. In addition, recent studies suggest that the transmission of semen-associated microbes into the female reproductive tract during mating has potentials to not only influence female fertility and embryo development but could also contribute to paternal programming in the offspring. In this review, we summarize the current knowledge on the seminal microbiota in both humans and animals followed by discussing their potential involvement in paternal programming of offspring health. We also propose and discuss potential mechanisms through which paternal influences are transmitted to offspring via the seminal microbiome. Overall, this review provides insights into the seminal microbiome-based paternal programing, which will expand our understanding of the potential paternal programming mechanisms which are currently focused primarily on the epigenetic modifications, oxidative stresses, and cytokines.

Prenatal Exposure to Severe Stress and the Risk of Heart Failure Up to Middle-Age.

BACKGROUND: Prenatal stress is a potential risk factor for cardiovascular disease, but its association with heart failure (HF) is unknown. OBJECTIVES: The purpose of this study was to investigate whether prenatal stress, defined as maternal bereavement, was associated with HF risk up to middle-age. METHODS: This cohort study included 6,758,560 live singleton births from the Danish (1973-2016) and the Swedish (1973-2014) Medical Birth Registers. The authors retrieved information on death of the mothers' close family members (partner, older children, parents, and siblings) and offspring's HF (up to 2016 in Denmark and 2020 in Sweden) from nationwide registers. They estimated HRs and 95% CIs for HF in the offspring according to maternal bereavement. RESULTS: During up to 48 years of follow-up, 4,812 offspring (0.07%) had a diagnosis of HF. Maternal loss of any close family member was not associated with HF in the offspring (adjusted HR: 1.04; 95% CI: 0.88-1.23). However, the most severe forms of bereavement, ie, death of a partner or an older child (adjusted HR: 1.47; 95% CI: 1.06-2.04) and unnatural death of a relative (adjusted HR: 2.77; 95% CI: 1.49-5.17), were associated with increased risks of HF. Congenital heart disease and preterm birth contributed substantially to the association of maternal loss of a partner or older child with HF risk in the offspring. CONCLUSIONS: Maternal loss of a partner or older child and loss of a close relative caused by unnatural causes the year before or during pregnancy were associated with increased risk of HF in offspring.

Prenatal maternal stress, child internalizing and externalizing symptoms, and the moderating role of parenting: findings from the Norwegian mother, father, and child cohort study.

BACKGROUND: Few studies have examined how parenting influences the associations between prenatal maternal stress and children's mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations. METHODS: This study is based on 15 963 mother-child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques. RESULTS: Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased. CONCLUSIONS: This study confirms associations between prenatal maternal stress and children's mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats.

Fetal undernutrition predisposes to hypertension development. Since nitric oxide (NO) is a key factor in blood pressure control, we aimed to investigate the role of NO alterations in hypertension induced by fetal undernutrition in rats. Male and female offspring from dams exposed to undernutrition during the second half of gestation (MUN) were studied at 21 days (normotensive) and 6 months of age (hypertension developed only in males). In aorta, we analyzed total and phosphorylated endothelial NO synthase (eNOS, p-eNOS), 3-nitrotyrosine (3-NT), and Nrf2 (Western blot). In plasma we assessed L-arginine, asymmetric and symmetric dimethylarginine (ADMA, SDMA; LC-MS/MS), nitrates (NOx, Griess reaction), carbonyl groups, and lipid peroxidation (spectrophotometry). In iliac arteries, we studied superoxide anion production (DHE staining, confocal microscopy) and vasodilatation to acetylcholine (isometric tension). Twenty-one-day-old MUN offspring did not show alterations in vascular e-NOS or 3NT expression, plasma L-Arg/ADMA ratio, or NOx. Compared to control group, 6-month-old MUN rats showed increased aortic expression of p-eNOS/eNOS and 3-NT, being Nrf2 expression lower, elevated plasma L-arginine/ADMA, NOx and carbonyl levels, increased iliac artery DHE staining and reduced acetylcholine-mediated relaxations. These alterations in MUN rats were sex-dependent, affecting males. However, females showed some signs of endothelial dysfunction. We conclude that increased NO production in the context of a pro-oxidative environment, leads to vascular nitrosative damage and dysfunction, which can participate in hypertension development in MUN males. Females show a better adaptation, but signs of endothelial dysfunction, which can explain hypertension in ageing.

Maternal iron status in early pregnancy and childhood body fat measures and cardiometabolic risk factors: A population-based prospective cohort.

BACKGROUND: Whether maternal iron status during pregnancy is associated with cardiometabolic health in the offspring is poorly known. OBJECTIVES: We aimed to assess the associations of maternal iron status during early pregnancy with body fat measures and cardiometabolic risk factors in children aged 10 y. METHODS: In a population-based cohort study among 3718 mother-child pairs, we measured ferritin, transferrin, and transferrin saturation during early pregnancy. We obtained child BMI, fat mass index, and android/gynoid fat mass ratio by DXA, subcutaneous fat index, visceral fat index, pericardial fat index, and liver fat fraction by magnetic resonance imaging and assessed systolic and diastolic blood pressure, serum lipids, glucose, insulin, and CRP at 10 y. RESULTS: A one-standard deviation score (SDS) higher maternal ferritin was associated with lower fat mass index [difference -0.05 (95% CI: -0.08, -0.02) SDS] and subcutaneous fat index [difference -0.06 (95% CI: -0.10, -0.02) SDS] in children. One-SDS higher maternal transferrin was associated with higher fat mass index [difference 0.04 (95% CI: 0.01, 0.07) SDS], android/gynoid fat mass ratio [difference 0.05 (95% CI: 0.02, 0.08) SDS], and subcutaneous fat index [difference 0.06 (95% CI: 0.02, 0.10) SDS] in children. Iron status during pregnancy was not consistently associated with organ fat and cardiometabolic risk factors at 10 y. CONCLUSIONS: Maternal lower ferritin and higher transferrin in early pregnancy are associated with body fat accumulation and distribution but are not associated with cardiometabolic risk factors in childhood. Underlying mechanisms and long-term consequences warrant further study.

Fetal glycated albumin levels in offspring of obese women.

OBJECTIVE: To determine the association between maternal obesity and fetal glycated albumin (GA) levels among pregnant women. METHODS: A comparative, cross-sectional study of 59 consenting, normoglycemic, pregnant women, who met the criteria for maternal obesity, attending the antenatal clinic of the University College Hospital, Nigeria, from June 2019 to December 2019. They were recruited at 36 weeks of gestation, followed up until delivery, and compared with 58 nonobese, normoglycemic pregnant controls. At delivery, blood samples were taken from the mothers and from the umbilical cords of their newborns for serum GA assay. Maternal and newborn variables were recorded, and comparisons were made using χ2 tests, independent t tests, odds ratios, analysis of variance, and Pearson correlates. Statistical significance was set at P < 0.05. RESULTS: The odds of elevated newborn GA were 3.21 times higher in obese women compared with nonobese women (P = 0.005) and 5-min APGAR scores were higher in the newborns of nonobese women (P = 0.039). There was a significant correlation between maternal and neonatal GA for all participants (r = 0.346, P = 0.000). CONCLUSION: These findings suggest that maternal obesity is associated with elevated fetal GA and low APGAR scores at 5 min in normoglycemic women.

Long-term effects of prenatal undernutrition on female rat hypothalamic KNDy neurons.

The nutritional environment during development periods induces metabolic programming, leading to metabolic disorders and detrimental influences on human reproductive health. This study aimed to determine the long-term adverse effect of intrauterine malnutrition on the reproductive center kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) of female offspring. Twelve pregnant rats were divided into ad-lib-fed (control, n = 6) and 50% undernutrition (UN, n = 6) groups. The UN group was restricted to 50% daily food intake of the control dams from gestation day 9 until term delivery. Differences between the two groups in terms of various maternal parameters, including body weight (BW), pregnancy duration, and litter size, as well as birth weight, puberty onset, estrous cyclicity, pulsatile luteinizing hormone (LH) secretion, and hypothalamic gene expression of offspring, were determined. Female offspring of UN dams exhibited low BW from birth to 3 weeks, whereas UN offspring showed signs of precocious puberty; hypothalamic Tac3 (a neurokinin B gene) expression was increased in prepubertal UN offspring, and the BW at the virginal opening was lower in UN offspring than that in the control group. Interestingly, the UN offspring showed significant decreases in the number of KNDy gene-expressing cells after 29 weeks of age, but the number of ARC kisspeptin-immunoreactive cells, pulsatile LH secretions, and estrous cyclicity were comparable between the groups. In conclusion, intrauterine undernutrition induced various changes in KNDy gene expression depending on the life stage. Thus, intrauterine undernutrition affected hypothalamic developmental programming in female rats.

Clinical aspects of decidualization / A decidualizáció klinikai vonatkozásai

An essential component of successful conception and pregnancy is decidualization, which involves structural and functional transformation of the endometrium. The process involves structural changes in the uterine mucosa, transformation of spiral arterioles, numerical and functional adaptation of leukocytes in the endometrium and their subsequent migration, and functional and morphological changes in decidual stromal cells. As part of decidualization, trophoblast cells of embryonic origin perform a physiological invasion of maternal tissue to create the placenta. The success of the process is due to the special antigenicity of the trophoblast cells and the immune communication between the graft (fetus) and the host (mother) through hormones, cytokines and multiple receptorligand connections. Disorders of these processes are the basis of several diseases that threaten conception, implantation, and successful pregnancy, such as recurrent miscarriage, preeclampsia, intrauterine retardation, or preterm birth. In this article, we review the anatomical, immunological, and molecular basis of physiological decidualization to address common disorders in the clinical practice of obstetrics that are related to a dysfunctional decidualization.

Prenatal disruption of blood-brain barrier formation via cyclooxygenase activation leads to lifelong brain inflammation.

Gestational maternal immune activation (MIA) in mice induces persistent brain microglial activation and a range of neuropathologies in the adult offspring. Although long-term phenotypes are well documented, how MIA in utero leads to persistent brain inflammation is not well understood. Here, we found that offspring of mothers treated with polyriboinosinic­polyribocytidylic acid [poly(I:C)] to induce MIA at gestational day 13 exhibit blood­brain barrier (BBB) dysfunction throughout life. Live MRI in utero revealed fetal BBB hyperpermeability 2 d after MIA. Decreased pericyte­endothelium coupling in cerebral blood vessels and increased microglial activation were found in fetal and 1- and 6-mo-old offspring brains. The long-lasting disruptions result from abnormal prenatal BBB formation, driven by increased proliferation of cyclooxygenase-2 (COX2; Ptgs2)-expressing microglia in fetal brain parenchyma and perivascular spaces. Targeted deletion of the Ptgs2 gene in fetal myeloid cells or treatment with the inhibitor celecoxib 24 h after immune activation prevented microglial proliferation and disruption of BBB formation and function, showing that prenatal COX2 activation is a causal pathway of MIA effects. Thus, gestational MIA disrupts fetal BBB formation, inducing persistent BBB dysfunction, which promotes microglial overactivation and behavioral alterations across the offspring life span. Taken together, the data suggest that gestational MIA disruption of BBB formation could be an etiological contributor to neuropsychiatric disorders.

Prenatal exposure to maternal psychological distress and telomere length in childhood.

Telomere length (TL) is a biological marker of cellular aging, and shorter TL in adulthood is associated with increased morbidity and mortality risk. It is likely that these differences in TL are established long before adulthood, and there is growing evidence that TL can reflect prenatal experiences. Although maternal prenatal distress predicts newborn TL, it is unknown whether the relation between prenatal exposure to maternal distress and child TL persists through childhood. The purpose of the current longitudinal, prospective study is to examine the relation between prenatal exposure to maternal distress (perceived stress, depressive symptoms, pregnancy-related anxiety) and TL in childhood. Participants included 102 children (54 girls) and their mothers. Mothers' distress was assessed five times during pregnancy, at 12 weeks postpartum, and at the time of child telomere measurement between 6 and 16 years of age. Maternal distress during pregnancy predicted shorter offspring TL in childhood, even after accounting for postnatal exposure to maternal distress and other covariates. These findings indicate that maternal mental health predicts offspring TL biology later in childhood than previously observed. This study bolsters claims that telomere biology is subject to fetal programming and highlights the importance of supporting maternal mental health during pregnancy.

Sources of heterogeneity when studying the cardiovascular effects of fetal growth restriction: an overview of the issues.

Intrauterine growth restriction (IUGR) has been repeatedly identified as a risk factor for cardiovascular disease (CVD). A possible explanation for this association is the effect of IUGR on cardiovascular structure and function. However, the specific changes observed are not consistent among studies. In this paper, we analyze several sources of heterogeneity within and between studies related to exposure, outcome and co-variables. A broad IUGR definition might include different phenotypes, expressing heterogeneity as an outcome. Outcome heterogeneity may also be the result of the postnatal effect modification that can be explored within studies. In order to do so, it is important to move beyond mean differences between groups, for example using unsupervised, stratified or interaction analysis. Different definitions of IUGR and the inclusion of different postnatal variables as confounders are potential sources of heterogeneity between studies. Researchers should be aware that postnatal variables may play different roles throughout a person's life and are not limited to behave as confounders. Therefore, their inclusion in the statistical model needs to be carefully considered. We discuss when sources of heterogeneity need to be controlled, and when they need to be identified and shown as a result.

In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels.

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6-7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

Early Appearance of Epicardial Adipose Tissue through Human Development.

Background: Epicardial adipose tissue (EAT) is a visceral fat depot with unique anatomic, biomolecular and genetic features. Due to its proximity to the coronary arteries and myocardium, dysfunctional EAT may contribute to the development and progression of cardiovascular and metabolic-related adiposity-based chronic diseases. The aim of this work was to describe, by morphological techniques, the early origin of EAT. Methods: EAT adipogenesis was studied in 41 embryos from 32 gestational days (GD) to 8 gestational weeks (GW) and in 23 fetuses until full term (from 9 to 36 GW). Results: This process comprises five stages. Stage 1 appears as mesenchyme at 33-35 GD. Stage 2 is characterized by angiogenesis at 42-45 GD. Stage 3 covers up to 34 GW with the appearance of small fibers in the extracellular matrix. Stage 4 is visible around the coronary arteries, as multilocular adipocytes in primitive fat lobules, and Stage 5 is present with unilocular adipocytes in the definitive fat lobules. EAT precursor tissue appears as early as the end of the first gestational month in the atrioventricular grooves. Unilocular adipocytes appear at the eighth gestational month. Conclusions: Due to its early origin, plasticity and clinical implications, factors such as maternal health and nutrition might influence EAT early development in consequence.

Programming by Methyl Donor Deficiency during Pregnancy and Lactation Produces Cardiomyopathy in Adult Rats Subjected to High Fat Diet.

SCOPE: Vitamin B12 and folate (methyl donors) deficiency is frequent during pregnancy. Experimental rat models with methyl donor deficit during pregnancy and lactation (Initial methyl donor deficit (iMDD)) produce impaired myocardium fatty acid oxidation and mitochondrial energy metabolism at weaning. METHODS AND RESULTS: The consequences of iMDD on heart of rat pups under normal diet after weaning and high fat diet (HF) between day (D) 50 and D185 are investigated. iMDD/HF induces increased histological fibrosis and increased B-type natriuretic peptide blood level. Inflammation is evidenced by increased protein expression of NFkB, Caspase1, and IL1ß and fibrosis by increased expression of αSMA, col1a1, and col1a2 in females, but not in males. Fibrosis is related to increased angiotensin at D50 and D185 and increased protein expression of TGFB1 and AT1 angiotensin receptors at D185. The limited fibrosis in males is consistent with increased expression of AT2, the antagonist receptor of AT1. The increased expression of GLUT4 and decreased expression of PGC1α and PPARα reflect a shift from fatty acid oxidation to glycolysis. CONCLUSION: Developmental programming by iMDD produces cardiomyopathy in female offspring exposed to HF. The cardiomyopathy is linked to inflammation and fibrosis through angiotensin-AT2 and TGFB1 pathways and alteration of energy metabolism.

Maternal selenium deficiency in mice promotes sex-specific changes to urine flow and renal expression of mitochondrial proteins in adult offspring.

Selenium deficiency during pregnancy can impair fetal development and predispose offspring to thyroid dysfunction. Given that key selenoproteins are highly expressed in the kidney and that poor thyroid health can lead to kidney disease, it is likely that kidney function may be impaired in offspring of selenium-deficient mothers. This study utilized a mouse model of maternal selenium deficiency to investigate kidney protein glycation, mitochondrial adaptations, and urinary excretion in offspring. Female C57BL/6 mice were fed control (>190 µg selenium/kg) or low selenium (<50 µg selenium/kg) diets four weeks prior to mating, throughout gestation, and lactation. At postnatal day (PN) 170, offspring were placed in metabolic cages for 24 hr prior to tissue collection at PN180. Maternal selenium deficiency did not impact selenoprotein antioxidant activity, but increased advanced glycation end products in female kidneys. Male offspring had reduced renal Complex II and Complex IV protein levels and lower 24 hr urine flow. Although renal aquaporin 2 (Aqp2) and arginine vasopressin receptor 2 (Avpr2) mRNA were not altered by maternal selenium deficiency, a correlation between urine flow and plasma free T4 concentrations in male but not female offspring suggests that programed thyroid dysfunction may be mediating impaired urine flow. This study demonstrates that maternal selenium deficiency can lead to long-term deficits in kidney parameters that may be secondary to impaired thyroid dysfunction. Considering the significant burden of renal dysfunction as a comorbidity to metabolic diseases, improving maternal selenium intake in pregnancy may be one simple measure to prevent lifelong disease.

Effects of maternal and fetal choline concentrations on the fetal growth and placental DNA methylation of 12 target genes related to fetal growth, adipogenesis, and energy metabolism.

AIM: We performed a birth cohort study involving 124 mother-infant pairs to investigate whether placental DNA methylation is associated with maternal choline status and fetal development. METHODS: Plasma choline concentration was assayed longitudinally in the 1st and 3rd trimesters and at term-pregnancy in mothers and cord blood. Placental DNA methylation was measured for 12 target candidate genes that are related to fetal growth, adipogenesis, lipid and energy metabolism, or long interspersed nuclear elements. RESULTS: Higher maternal plasma and cord blood choline levels at term tended to associate with lower birthweight (r = -0.246, P < 0.013; r = -0.290, P < 0.002) and body mass index (BMI) at birth (r = 0.344, P < 1E-3; r = -0.360, P < 1E-3). The correlation between maternal plasma choline level and cord blood choline level was relatively modest (r = 0.049, P = 0.639). There was an inverse correlation between placental DNA methylation at the retinoid X receptor alpha (RXRA) gene and maternal plasma choline level (r = -0.188 to r = -0.452, P = 0.043 to P < 1E-3 at three points). RXRA methylation level was positively associated with birthweight and BMI at birth (r = 0.306, P = 0.001; r = 0.390, P < 1E-3). Further, RXRA methylation was inversely correlated with RXRA gene expression level (r = 0.333, P < 1E-3). CONCLUSION: Our results suggest that the association between maternal choline status and placental RXRA methylation represents a potential fetal programing mechanism contributing to fetal growth.

Maternal Choline Intake Programs Hypothalamic Energy Regulation and Later-Life Phenotype of Male Wistar Rat Offspring.

SCOPE: High-folic-acid diets during pregnancy result in obesity in the offspring, associated with altered DNA-methylation of hypothalamic food intake neurons. Like folic acid, the methyl-donor choline modulates foetal brain development, but its long-term programing effects on energy regulation remain undefined. This study aims to describe the effect of choline intake during pregnancy on offspring phenotype and hypothalamic energy-regulatory mechanisms. METHODS AND RESULTS: Wistar rat dams are fed an AIN-93G diet with recommended choline (RC, 1 g kg-1 diet), low choline (LC, 0.5-fold), or high choline (HC, 2.5-fold) during pregnancy. Male pups are terminated at birth and 17 weeks post-weaning. Brain 1-carbon metabolites, body weight, food intake, energy expenditure, plasma hormones, and protein expression of hypothalamic neuropeptides are measured. HC pups have higher expression of the orexigenic neuropeptide-Y neurons at birth, consistent with higher cumulative food intake and body weight gain post-weaning compared to RC and LC offspring. LC pups have lower leptin receptor expression at birth and lower energy expenditure and activity during adulthood. CONCLUSION: Choline content of diets that are consumed by rats during pregnancy affects the later-life phenotype of offspring, associated with altered in utero programing of hypothalamic food intake regulation.

Maternal and gestational influences on childhood blood pressure.

Exposures that contribute to a sub-optimal intrauterine environment can have an effect on the developing fetus. Impaired fetal growth that results in low birth weight is an established risk factor for cardio-metabolic disorders later in life. Recent epidemiologic and prospective cohort studies that include the maternal and gestational period have identified maternal and gestational conditions that confer increased risk for subsequent cardio-metabolic disorders in the absence of low birth weight. Maternal pre-conception health status, including chronic obesity and type 2 diabetes, increase risk for childhood obesity and obesity-related higher blood pressure (BP) in child offspring. Maternal gestational exposures, including gestational diabetes, gestational hypertension, and preeclampsia, are associated with higher BP in offspring. Other maternal exposures such as cigarette smoke and air pollution also increase risk for higher BP in child offspring. Recent, but limited, data indicate that assisted reproductive technologies can be associated with hypertension in childhood, despite otherwise normal gestation and healthy newborn. Gestational exposures associated with higher BP in childhood can be related to familial lifestyle factors, genetics, or epigenetic modification of fetal deoxyribonucleic acid (DNA). These factors, or combination of factors, as well as other adverse intrauterine conditions, could induce fetal programing leading to health consequences in later life. Current and developing research will provide additional insights on gestational exposures and fetal adjustments that increase risk for higher BP levels in childhood.