Desai Swapna, Rajkovic Aleksandar
Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Semin Reprod Med. 2017 Mar;35(2):147-159. doi: 10.1055/s-0037-1599086. Epub 2017 Mar 9.
Reproduction is essential for the survival of the species and is influenced by external factors such as smoking and exposure to chemotherapy as well as chronic disorders such as obesity and autoimmunity. Reproductive senescence, such as menopause, is also dependent on multiple intrinsic genetic factors. Reproductive aging is not isolated from an overall aging process, and several studies strongly support the link between the early age of menopause and mortality. The extreme form of reproductive aging is primary ovarian insufficiency (POI) with prevalence ranging from 1 to 5% of the female population. POI has been shown to have long-term consequences on overall health. POI and age of menopause have a significant hereditary component. The population-based genome-wide association studies have identified 44 genomic loci to associate with age of menopause, and 29 of 44 loci harbor DNA damage response genes. Recent application of whole exome sequencing on carefully selected families with POI has also revealed a significant contribution of DNA damage response genes. The inability to repair the DNA damage in both somatic and germ cells might be a predisposing factor for the link between reproductive and overall aging in a subset of individuals with POI. The aim of this review is to characterize recent advances in the genetics of POI and its link with overall health.
生殖对于物种的生存至关重要，它受到吸烟、接触化疗等外部因素以及肥胖和自身免疫等慢性疾病的影响。生殖衰老，如更年期，也依赖于多种内在遗传因素。生殖衰老并非与整体衰老过程孤立存在，多项研究有力地支持了早发性更年期与死亡率之间的联系。生殖衰老的极端形式是原发性卵巢功能不全（POI），其在女性人群中的患病率为1%至5%。POI已被证明会对整体健康产生长期影响。POI和更年期年龄具有显著的遗传成分。基于人群的全基因组关联研究已确定44个基因组位点与更年期年龄相关，其中44个位点中的29个含有DNA损伤反应基因。最近对精心挑选的POI家族进行的全外显子组测序也揭示了DNA损伤反应基因的重要作用。在一部分POI个体中，体细胞和生殖细胞中DNA损伤无法修复可能是生殖衰老与整体衰老之间联系的一个易感因素。本综述的目的是阐述POI遗传学的最新进展及其与整体健康的联系。
