Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Karolinska Institute, Stockholm, Sweden, Nova Southeastern University, Fort Lauderdale, FL, USA.
Trends Endocrinol Metab. 2018 Jun;29(6):400-419. doi: 10.1016/j.tem.2018.03.010. Epub 2018 Apr 26.
Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.
原发性卵巢功能不全（POI）影响了约 1%的 40 岁以下女性。下一代测序（NGS）和动物模型获得的最新基因知识飞跃进一步阐明了其分子发病机制，确定了新的基因/途径。超过 60 个基因的突变强调了高度的遗传异质性。全基因组关联研究揭示了 POI 和生殖衰老之间的共同遗传背景。NGS 将提供遗传诊断，从而进行遗传/治疗咨询：首先，减数分裂或 DNA 修复基因的缺陷可能导致肿瘤；其次，特定的基因缺陷可能预测持续卵巢储备迅速丧失的风险，这是生育力保存的一个重要决定因素。事实上，最近通过体外激活休眠卵泡对 POI 的创新性治疗已被证明是成功的。
