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Nat Rev Endocrinol. 2015 Dec;11(12):725-34. doi: 10.1038/nrendo.2015.167. Epub 2015 Oct 13.

Molecular insights into the aetiology of female reproductive ageing.

Author information

1
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
2
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon &Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK.

Abstract

As age at pubertal onset declines and age at first pregnancy increases, the mechanisms that regulate female reproductive lifespan become increasingly relevant to population health. The timing of menarche and menopause can have profound effects not only on fertility but also on the risk of diseases such as type 2 diabetes mellitus, cardiovascular disease and breast cancer. Genetic studies have identified dozens of highly penetrant rare mutations associated with reproductive disorders, and also ∼175 common genetic variants associated with the timing of puberty or menopause. These findings, alongside other functional studies, have highlighted a diverse range of mechanisms involved in reproductive ageing, implicating core biological processes such as cell cycle regulation and energy homeostasis. The aim of this article is to review the contribution of such genetic findings to our understanding of the molecular regulation of reproductive timing, as well as the biological basis of the epidemiological links between reproductive ageing and disease risk.

PMID:
26460341
DOI:
10.1038/nrendo.2015.167
[Indexed for MEDLINE]
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