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Maternal oxytocin treatment at birth increases epigenetic age in male offspring [array]

ABSTRACT: 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.

ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens Microtus ochrogaster

PROVIDER: GSE240833 | GEO | 2024/04/03

REPOSITORIES: GEO

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Project description:Background Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution of egocentric network sizes (characterized by number of different partners encountered per day). We then used RNA-seq to perform an unbiased assessment of neural differences in gene expression in the prefrontal cortex, the hippocampus and the hypothalamus between these mice with naturally occurring extreme differences in social network size. Results We found that the neurogenomic pathways associated with having extreme social network sizes differed between the sexes. In females, hundreds of genes were differentially expressed between animals with small and large social network sizes, whereas in males very few were. In males, X-chromosome inactivation pathways in the prefrontal cortex were the ones that better differentiated animals with small from those with large social network sizes animals. In females, animals with small network size showed up-regulation of dopaminergic production and transport pathways in the hypothalamus. Additionally, in females, extracellular matrix deposition on hippocampal neurons was higher in individuals with small relative to large social network size. Conclusions Studying neural substrates of natural variation in social behavior in traditional model organisms in their habitat can open new targets of research for understanding variation in social behavior in other taxa.

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Maternal oxytocin treatment at birth increases epigenetic age in male offspring [array]

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