Unravelling the role of epigenetics in reproductive adaptations to early-life environment

Melamed, Philippa; Bar-Sadeh, Ben; Rudnizky, Sergei; Pnueli, Lilach; Bentley, Gillian; Stoger, Reinhard; Kaplan, Ariel

Abstract

Reproductive function adjusts in response to environmental conditions in order to optimize success. In humans, this plasticity includes age of pubertal onset, hormone levels and age at menopause. These reproductive characteristics vary across populations with distinct lifestyles and following specific childhood events, and point to a role for the early-life environment in shaping adult reproductive trajectories. Epigenetic mechanisms respond to external signals, exert long-term effects on gene expression and have been shown in animal and cellular studies to regulate normal reproductive function, strongly implicating their role in these adaptations. Moreover, human cohort data have revealed differential DNA methylation signatures in proxy tissues that are associated with reproductive phenotypic variation, although the cause–effect relationships are difficult to discern, calling for additional complementary approaches to establish functionality. In this Review, we summarize how adult reproductive function can be shaped by childhood events. We discuss why the influence of the childhood environment on adult reproductive function is an important consideration in understanding how reproduction is regulated and necessitates consideration by clinicians treating women with diverse life histories. The resolution of the molecular mechanisms responsible for human reproductive plasticity could also lead to new approaches for intervention by targeting these epigenetic modifications.

Citation

Melamed, P., Bar-Sadeh, B., Rudnizky, S., Pnueli, L., Bentley, G., Stoger, R., & Kaplan, A. (2020). Unravelling the role of epigenetics in reproductive adaptations to early-life environment. Nature Reviews Endocrinology, 16, 519-533. https://doi.org/10.1038/s41574-020-0370-8

• Journal Article Type: Article
• Acceptance Date: May 11, 2020
• Online Publication Date: Jul 11, 2020
• Publication Date: 2020
• Deposit Date: May 13, 2020
• Publicly Available Date: Jan 3, 2021
• Journal: Nature Reviews Endocrinology
• Print ISSN: 1759-5029
• Electronic ISSN: 1759-5037
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Pages: 519-533
• DOI: https://doi.org/10.1038/s41574-020-0370-8
• Public URL: https://durham-repository.worktribe.com/output/1270932