Perry John R B, Murray Anna, Day Felix R, Ong Ken K
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon &Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK.
Nat Rev Endocrinol. 2015 Dec;11(12):725-34. doi: 10.1038/nrendo.2015.167. Epub 2015 Oct 13.
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.
随着青春期开始年龄下降而首次怀孕年龄增加，调节女性生殖寿命的机制与人群健康的相关性日益增强。月经初潮和绝经的时间不仅会对生育能力产生深远影响，还会影响2型糖尿病、心血管疾病和乳腺癌等疾病的发病风险。基因研究已经确定了数十种与生殖障碍相关的高外显率罕见突变，以及约175种与青春期或绝经时间相关的常见基因变异。这些发现以及其他功能研究突出了参与生殖衰老的多种机制，涉及细胞周期调控和能量稳态等核心生物学过程。本文旨在综述这些基因研究结果对我们理解生殖时间分子调控的贡献，以及生殖衰老与疾病风险之间流行病学联系的生物学基础。
