Project description:Exogenous oxytocin (OT) is widely used to induce or augment labor with little understanding of the impact on offspring development. In rodent models, including the prairie vole (Microtus ochrogaster), it has been shown that oxytocin administered to mothers can affect the nervous system of the offspring with long lasting behavioral effects especially on sociality. Here, we examined the hypothesis that perinatal oxytocin exposure could have epigenetic and transcriptomic consequences. Prairie voles were exposed to exogenous oxytocin, through injections given to the mother just prior to birth, and were studied at the time of weaning. The outcome of this study revealed increased epigenetic age in oxytocin-exposed animals compared to the saline-exposed group. Oxytocin exposure led to 900 differentially methylated CpG sites (annotated to 589 genes), and 2 CpG sites (2 genes) remained significantly different after correction for multiple comparisons. Differentially methylated CpG sites were enriched in genes known to be involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we also found 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons 6 genes remained significantly differentially expressed. Finally, we found that maternal oxytocin administration led to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth may have long lasting epigenetic consequences. A need for further investigation of how oxytocin administration impacts development and behavior throughout the lifespan is supported by these outcomes.
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.
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.
Project description:PurposeInvestigate associations of maternal social experiences with offspring epigenetic age acceleration (EAA) from birth through mid-childhood among 205 mother-offspring dyads of minoritized racial and ethnic groups.MethodsWe used linear regression to examine associations of maternal experiences of racial bias or discrimination (0 = none, 1-2 = intermediate, or 3+ = high), social support (tertile 1 = low, 2 = intermediate, 3 = high), and socioeconomic status index (tertile 1 = low, 2 = intermediate, 3 = high) during the prenatal period with offspring EAA according to Horvath's Pan-Tissue, Horvath's Skin and Blood, and Intrinsic EAA clocks at birth, 3 years, and 7 years.ResultsIn comparison to children of women who did not experience any racial bias or discrimination, those whose mothers reported highest levels of racial bias or discrimination had lower Pan-Tissue clock EAA in early (-0.50 years; 90% CI: -0.91, -0.09) and mid-childhood (-0.75 years; -1.41, -0.08). We observed similar associations for the Skin and Blood clock and Intrinsic EAA. Maternal experiences of discrimination were not associated with Pan-Tissue EAA at birth. Neither maternal social support nor socioeconomic status predicted offspring EAA.ConclusionsChildren whose mothers experienced higher racial bias or discrimination exhibited slower EAA. Future studies are warranted to confirm these findings and establish associations of early-life EAA with long-term health outcomes.
Project description:Maternal pregnancy fatty acid status is associated with child health. Epigenetic gestational age acceleration, referring to a discrepancy between chronological and epigenetic gestational age, may underlie these associations. Previous research suggests that analysing fatty acid patterns rather than individual fatty acids may overcome the caveat of missing synergistic or additive effects. Among 1226 mother-newborn pairs from the population-based Generation R Study, we examined the associations of three maternal plasma mid-pregnancy fatty acid patterns, identified by principal component analysis, with offspring epigenetic gestational age acceleration. This was estimated from cord blood DNA methylation data using the method developed by Bohlin. As a secondary analysis, we used the method developed by Knight to estimate epigenetic gestational age. The identified 'high n-6 polyunsaturated fatty acid,' 'monounsaturated and saturated fatty acid' and 'high n-3 polyunsaturated fatty acid' patterns were not associated with epigenetic gestational age acceleration in the main analyses. In sensitivity analyses restricted to 337 children born to mothers with more accurate pregnancy dating based on a regular menstrual cycle, a one standard-deviation-score higher maternal plasma 'high n-3 polyunsaturated fatty acid' pattern was associated with an epigenetic gestational age acceleration of 0.20 weeks (95% CI 0.06, 0.33), but only when using the Knight method. Thus, we found some evidence that a maternal plasma fatty acid pattern characterized by higher concentrations of n-3 polyunsaturated fatty acids may be associated with accelerated epigenetic gestational ageing. These findings depended on the method used and the accuracy of pregnancy dating and therefore need confirmation.
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.
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.