Maternal Oxytocin Treatment at Birth Increases Epigenetic Age in Male Offspring

We are thrilled to announce a successful collaboration between VUGENE team – Juozas Gordevičius, Milda Milčiūtė, the Clock Foundation, and the University of Virginia, uncovering the long-lasting effects of exogenous oxytocin on infant development.

Exogenous oxytocin, commonly used during labor, has been a topic of debate regarding its influence on offspring development. This study, centered on prairie voles (Microtus ochrogaster), sheds light on the complex interplay between perinatal oxytocin exposure and its potential epigenetic and transcriptomic outcomes. The study revealed that oxytocin exposure during birth led to increased epigenetic age in the exposed animals compared to the control group that received saline.

These findings highlight the necessity for further exploration into oxytocin’s effects on development and behavior throughout life. The implications stretch beyond rodent models, urging a deeper understanding of oxytocin’s role in human development and health.

Abstract

Exogenous oxytocin 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 two CpG sites (two 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 < .05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons, six 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 life span is supported by these outcomes.

Danoff, J. S., Carter, C. S., Gordevičius, J., Milčiūtė, M., Brooke, R. T., Connelly, J. J., & Perkeybile, A. M. (2024). Maternal oxytocin treatment at birth increases epigenetic age in male offspring. Developmental Psychobiology, 66, e22452. 

Read full article: Link
Written by: Milda Milčiūtė
Cover image credits: sushytska / Adobe Stock

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