Huang Chengzi, Guo Ting, Qin Yingying
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China.
Front Cell Dev Biol. 2021 Mar 8;9:652407. doi: 10.3389/fcell.2021.652407. eCollection 2021.
Premature ovarian insufficiency (POI) is the depletion of ovarian function before 40 years of age due to insufficient oocyte formation or accelerated follicle atresia. Approximately 1-5% of women below 40 years old are affected by POI. The etiology of POI is heterogeneous, including genetic disorders, autoimmune diseases, infection, iatrogenic factors, and environmental toxins. Genetic factors account for 20-25% of patients. However, more than half of the patients were idiopathic. With the widespread application of next-generation sequencing (NGS), the genetic spectrum of POI has been expanded, especially the latest identification in meiosis and DNA repair-related genes. During meiotic prophase I, the key processes include DNA double-strand break (DSB) formation and subsequent homologous recombination (HR), which are essential for chromosome segregation at the first meiotic division and genome diversity of oocytes. Many animal models with defective meiotic recombination present with meiotic arrest, DSB accumulation, and oocyte apoptosis, which are similar to human POI phenotype. In the article, based on different stages of meiotic recombination, including DSB formation, DSB end processing, single-strand invasion, intermediate processing, recombination, and resolution and essential proteins involved in synaptonemal complex (SC), cohesion complex, and fanconi anemia (FA) pathway, we reviewed the individual gene mutations identified in POI patients and the potential candidate genes for POI pathogenesis, which will shed new light on the genetic architecture of POI and facilitate risk prediction, ovarian protection, and early intervention for POI women.
卵巢早衰（POI）是指由于卵母细胞形成不足或卵泡闭锁加速，导致40岁之前卵巢功能衰竭。约1-5%的40岁以下女性受POI影响。POI的病因具有异质性，包括遗传疾病、自身免疫性疾病、感染、医源性因素和环境毒素。遗传因素占患者的20-25%。然而，超过一半的患者病因不明。随着下一代测序（NGS）的广泛应用，POI的遗传谱得到了扩展，尤其是在减数分裂和DNA修复相关基因方面的最新发现。在减数分裂前期I，关键过程包括DNA双链断裂（DSB）形成及随后的同源重组（HR），这对于第一次减数分裂时的染色体分离和卵母细胞的基因组多样性至关重要。许多减数分裂重组缺陷的动物模型表现出减数分裂停滞、DSB积累和卵母细胞凋亡，这与人类POI表型相似。在本文中，基于减数分裂重组的不同阶段，包括DSB形成、DSB末端处理、单链侵入、中间处理、重组和分辨率，以及参与联会复合体（SC）、黏连复合体和范可尼贫血（FA）途径的必需蛋白质，我们综述了在POI患者中鉴定出的个体基因突变以及POI发病机制的潜在候选基因，这将为POI的遗传结构提供新的线索，并有助于对POI女性进行风险预测、卵巢保护和早期干预。
