Maternal oxytocin treatment at birth increases epigenetic age in male offspring
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens Microtus ochrogaster
PROVIDER: GSE240856 | GEO | 2024/04/03
REPOSITORIES: GEO
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Project description:Rates of oxytocin use to induce or augment labor are increasing in the United States with little understanding of the impact on offspring development. Using a prairie vole animal model, we have shown that oxytocin administered to mothers can reach offspring brains with long lasting impacts on the development of social behaviors. Here, we examine the epigenetic and transcriptomic consequences of oxytocin exposure during birth in juvenile male offspring. First, we show that male offspring exposed to oxytocin at birth have increased epigenetic age compared to the saline exposed group. We also find 900 differentially methylated CpG sites (annotated to 589 genes), with 2 CpG sites (2 genes) remaining significant after correction for multiple comparisons. Differentially methylated CpG sites are involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we find 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior, including 6 genes that remain significantly differentially expressed after corrections for multiple comparisons. Finally, we show that maternal oxytocin administration leads to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth has long lasting epigenetic consequences in the brain and warrant further investigation of how oxytocin administration impacts development and behavior throughout the lifespan.
2024-04-03 | GSE240833 | GEO
Project description:Rates of oxytocin use to induce or augment labor are increasing in the United States with little understanding of the impact on offspring development. Using a prairie vole animal model, we have shown that oxytocin administered to mothers can reach offspring brains with long lasting impacts on the development of social behaviors. Here, we examine the epigenetic and transcriptomic consequences of oxytocin exposure during birth in juvenile male offspring. First, we show that male offspring exposed to oxytocin at birth have increased epigenetic age compared to the saline exposed group. We also find 900 differentially methylated CpG sites (annotated to 589 genes), with 2 CpG sites (2 genes) remaining significant after correction for multiple comparisons. Differentially methylated CpG sites are involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we find 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior, including 6 genes that remain significantly differentially expressed after corrections for multiple comparisons. Finally, we show that maternal oxytocin administration leads to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth has long lasting epigenetic consequences in the brain and warrant further investigation of how oxytocin administration impacts development and behavior throughout the lifespan.
2024-04-03 | GSE240832 | GEO
Project description:Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism.
| S-EPMC6494504 | biostudies-literature
Project description:The mechanisms controlling genome methylation during human embryogenesis remain largely unknown. Here we provide evidence that maternal age at pregnancy permanently alters the epigenetic profile of offspring. We measured DNA methylation in blood at over 450,000 CpGs across the epigenome in 890 newborns.
2016-06-08 | GSE82273 | GEO
Project description:Vitamin D could be beneficial for healthy ageing in humans. We previously found that vitamin D supplementation may slow down epigenetic ageing in young African American adults. We tested new epigenetic clocks developed for neonates among a multiethnic population, and tested the hypothesis that maternal vitamin D supplementation would slow down the epigenetic gestational age acceleration (GAA) in newborn babies. Ninety-two pregnant women (aged 29.6 ± 4.8 y; 21% African Americans, 28% Hispanics) were randomized to receive 4000 IU/day vitamin D3 or placebo, plus prenatal vitamins containing 400 IU vitamin D3 during pregnancy in a randomized controlled trial (RCT). Cord blood genome-wide methylation analysis was performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age was calculated based on two calculations developed by Knight and Bohlin. DNA methylation gestational ages calculated by Knight's clock and Bohlin' clock were highly correlated with the gestational age in the placebo group (correlation coefficients = 0.88, p s< 0.001, respectively). GAA was associated with higher birth weight (p = 0.039). In the entire cohort, vitamin D3 supplementation was not associated with GAA (p > 0.05). However, vitamin D3 supplementation decreased GAA by both Knight's clock (β = -0.89, p = 0.047) and Bohlin's clock (β = -0.71, p = 0.005) in the African American participants. Maternal vitamin D3 supplementation may slow down the epigenetic gestational ageing process in African American neonates. Long-term follow-up studies are warranted to determine the role of epigenetic age acceleration in the growth and development of offspring.
| S-EPMC7518698 | biostudies-literature
Project description:Adverse birth outcomes, such as early gestational age and low birth weight, can have lasting effects on morbidity and mortality, with impacts that persist into adulthood. Identifying the maternal factors that contribute to adverse birth outcomes in the next generation is thus a priority. Epigenetic clocks, which have emerged as powerful tools for quantifying biological aging and various dimensions of physiological dysregulation, hold promise for clarifying relationships between maternal biology and infant health, including the maternal factors or states that predict birth outcomes. Nevertheless, studies exploring the relationship between maternal epigenetic age and birth outcomes remain few. Here, we attempt to replicate a series of analyses previously reported in a US-based sample, using a larger similarly aged sample (n = 296) of participants of a long-running study in the Philippines. New pregnancies were identified prospectively, dried blood spot samples were collected during the third trimester, and information was obtained on gestational age at delivery and offspring weight after birth. Genome-wide DNA methylation was assessed with the Infinium EPIC array. Using a suite of 15 epigenetic clocks, we only found one significant relationship: advanced age on the epigenetic clock trained on leptin predicted a significantly earlier gestational age at delivery (β = - 0.15, p = 0.009). Of the other 29 relationships tested predicting gestational age and offspring birth weight, none were statistically significant. In this sample of Filipino women, epigenetic clocks capturing multiple dimensions of biology and health do not predict birth outcomes in offspring.
| S-EPMC9219190 | biostudies-literature
Project description:Obesity during pregnancy increases the risk of cardiovascular problems, diabetes, asthma, and cognitive impairments, affecting the offspring. It is important to reduce the negative effects of obesity and high-fat (HF) diet during pregnancy. We employed a rat model of maternal HF diet to evaluate the possible de-programming effects of resveratrol in rodent male offspring with maternal HF diet/obesity. Male rat offspring were randomized into four groups: maternal control diet/postnatal control diet, maternal HF diet/postnatal control diet, maternal control diet plus maternal resveratrol treatment/postnatal control diet, and maternal HF diet plus maternal resveratrol treatment/postnatal control diet. Maternal HF diet during pregnancy plus lactation resulted in retroperitoneal adiposity in the male offspring. Maternal resveratrol treatment re-programmed maternal HF exposure-induced visceral adiposity. Offspring that received prenatal HF diet showed higher leptin/soluble leptin receptor (sOB-R) ratio than offspring that received prenatal control diet. Maternal resveratrol treatment ameliorated maternal HF exposure-induced increase in leptin/sOB-R ratio and altered the expression of genes for crucial fatty acid synthesis enzymes in the offspring. Thus, maternal resveratrol administration reduces retroperitoneal adiposity in rat offspring exposed to prenatal HF diet/obesity and could be used to ameliorate negative effects of maternal HF diet in the offspring.
| S-EPMC7215689 | biostudies-literature
Project description:BackgroundMaternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms.ObjectivesThe aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring.MethodsWistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet during pregnancy and lactation, and their male offspring were studied at 30 d of age. Direct measurements of baseline arterial blood pressure (ABP), heart rate (HR), and respiratory frequency (Rf) as well as peripheral chemoreflex activation (potassium cyanide: 0.04%) were recorded in pups while they were awake. In addition, recordings of the phrenic nerve (PN) and thoracic sympathetic nerve (tSN) activities were obtained from the in situ preparations. Hypoxia-inducible factor 1α (HIF-1α) expression was also evaluated in carotid bifurcation through a Western blotting assay.ResultsAt 30 d of age, unanesthetized LP rats exhibited enhanced resting Rf (P = 0.001) and similar ABP and HR compared with the NP rats. Despite their similar baseline ABP values, LP rats exhibited augmented low-frequency variability (∼91%; P = 0.01). In addition, the unanesthetized LP rats showed enhanced pressor (P = 0.01) and tachypnoeic (P = 0.03) responses to peripheral chemoreflex activation. The LP rats displayed elevated baseline tSN activity (∼86%; P = 0.02) and PN burst frequency (45%; P = 0.01) and amplitude (53%; P = 0.001) as well as augmented sympathetic (P = 0.01) and phrenic (P = 0.04) excitatory responses to peripheral chemoreflex activation compared with the NP group. Furthermore, LP rats showed an increase of ∼100% in HIF-1α protein density in carotid bifurcation compared with NP rats.ConclusionSympathetic-respiratory overactivity and amplified peripheral chemoreceptor responses, potentially through HIF-1α-dependent mechanisms, precede the onset of hypertension in juvenile rats exposed to protein undernutrition during gestation and lactation.
| S-EPMC6619683 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-31 | GSE242189 | GEO
Project description:ObjectiveMaternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposure induces changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period on neuronal plasticity and cardiometabolic health in adult offspring.MethodsC57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months resulting in 4 treatment groups that underwent cardiometabolic assessments. DNA and RNA were extracted from the hypothalamus to perform whole genome methylation, mRNA, and miRNA sequencing followed by bioinformatic analyses.ResultsMaternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed HCD in adulthood exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA, while genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. These data were supported by our findings of astrogliosis, microgliosis and increased microglial activation in programmed males in the paraventricular nucleus (PVN). Programming induced a protective effect in male mice fed HCD in adulthood, resulting in lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed males. Although TGFβ2 was upregulated in male mice exposed to HCD pre- or post-natally, only blockade of the brain TGFβ receptor in RD-HCD mice improved glucose tolerance and a trend to weight loss.ConclusionsOur study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia associated with hypothalamic inflammation in mechanisms and pathways distinct from post-natal HCD exposure. Together, our data unmask a compensatory role of HCD programming, likely via priming of metabolic pathways to handle excess nutrients in a more efficient way.
| S-EPMC10806294 | biostudies-literature