The impact of the early environment on oxytocin receptor epigenetics and potential therapeutic implications.

Abstract

Oxytocin research is rapidly evolving and increasingly reveals that epigenetic modifications to the oxytocin receptor gene (OXTR) are functional, plastic, and reliable components of oxytocinergic system function.

This review outlines how OXTR epigenetics are shaped by the early life environment, impact social-developmental outcomes, and have strong potential to serve as therapeutic targets.

We first establish the malleability of OXTR epigenetics in infancy in both animal models and humans through research demonstrating the impact of the early life environment on OXTR DNA methylation (OXTRm) and subsequent social behavior.

Next, we detail how OXTRm serves as a predictive mechanism for neurodevelopmental outcomes in animal models of social behavior such as the prairie vole, and summarize the role of OXTRm in psychiatric disorders, emotional processing, and attachment behavior in humans.

We discuss the potential of further OXTRm research to improve oxytocin therapeutics by highlighting how a deeper knowledge of OXTRm could improve the therapeutic potential of exogenous oxytocin, how OXTRm may impact additional cellular mechanisms with therapeutic potential including control of the perinatal GABA switch, and how early life therapies may target the tuning of endogenous OXTRm.

Finally, we review limitations of previous oxytocin research and make recommendations for future research.

IMPACT: Previous research into oxytocin therapeutics has been hampered by methodological difficulties that may be improved by assay of the oxytocin receptor gene (OXTR) and its methylation (OXTRm) Key sites of OXTRm modification link early life exposures to developmental and behavioral outcomes OXTRm appears to have a critical period of development in early life Epigenetic modification of the oxytocin receptor gene could serve as a powerful target for therapeutic interventions.

References:

Gimpl, G. & Fahrenholz, F. The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 81, 629–683 (2001).
Kendrick, Keith. M. Oxytocin, motherhood and bonding. Exp. Physiol. 85, 111S–124S (2000).
Uvnäs-Moberg, K. et al. Maternal plasma levels of oxytocin during physiological childbirth—a systematic review with implications for uterine contractions and central actions of oxytocin. BMC Pregnancy Childbirth 19, 285 (2019).
DeMayo, M. M., Song, Y. J. C., Hickie, I. B. & Guastella, A. J. A review of the safety, efficacy and mechanisms of delivery of nasal oxytocin in children: therapeutic potential for autism and Prader-Willi syndrome, and recommendations for future research. Paediatr. Drugs 19, 391–410 (2017).
Anagnostou, E. et al. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth. Brain Res. 1580, 188–198 (2014).

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10.1038/s41390-024-03563-z

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The impact of the early environment on oxytocin receptor epigenetics and potential therapeutic implications.

Abstract

This review outlines how OXTR epigenetics are shaped by the early life environment, impact social-developmental outcomes, and have strong potential to serve as therapeutic targets.

Finally, we review limitations of previous oxytocin research and make recommendations for future research.

References:

Gimpl, G. & Fahrenholz, F. The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 81, 629–683 (2001).
Kendrick, Keith. M. Oxytocin, motherhood and bonding. Exp. Physiol. 85, 111S–124S (2000).
Uvnäs-Moberg, K. et al. Maternal plasma levels of oxytocin during physiological childbirth—a systematic review with implications for uterine contractions and central actions of oxytocin. BMC Pregnancy Childbirth 19, 285 (2019).
DeMayo, M. M., Song, Y. J. C., Hickie, I. B. & Guastella, A. J. A review of the safety, efficacy and mechanisms of delivery of nasal oxytocin in children: therapeutic potential for autism and Prader-Willi syndrome, and recommendations for future research. Paediatr. Drugs 19, 391–410 (2017).
Anagnostou, E. et al. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth. Brain Res. 1580, 188–198 (2014).