卵巢衰老对生殖的影响:从端粒和小鼠模型到卵巢 rejuvenation。
Impact of Ovarian Aging in Reproduction: From Telomeres and Mice Models to Ovarian Rejuvenation.
机构信息
IVI Foundation, Valencia, Spain.
Instituto de Investigación Sanitaria La Fe., Valencia, Spain.
出版信息
Yale J Biol Med. 2020 Sep 30;93(4):561-569. eCollection 2020 Sep.
The trend in our society to delay procreation increases the difficulty to conceive spontaneously. Thus, there is a growing need to use assisted reproduction technologies (ART) to form a family. With advanced maternal age, ovaries not only produce a lower number of oocytes after ovarian stimulation but also a lower quality-mainly aneuploidies-requiring further complex analysis to avoid complications during implantation and pregnancy. Although there are different options to have a child at advanced maternal age (like donor eggs), this is not the preferred choice for most patients. Unless women had cryopreserved their eggs at a younger age, reproductive medicine should try to optimize their opportunities to become pregnant with their own oocytes, when chances of success are reasonable. Aging has many causes, but telomere attrition is ultimately one of the main pathways involved in this process. Several reports link telomere biology and reproduction, but the molecular reasons for the rapid loss of ovarian function at middle age are still elusive. This review will focus on the knowledge acquired during the last years about ovarian aging and disease, both in mouse models of reproductive senescence and in humans with ovarian failure, and the implication of telomeres in this process. In addition, the review will discuss recent results on ovarian rejuvenation, achieved with stem cell therapies that are currently under study, or ovarian reactivation by tissue fragmentation and the attempts to generate oocytes .
由于社会上普遍存在的晚育趋势,自然受孕的难度增加了。因此,人们越来越需要使用辅助生殖技术(ART)来组建家庭。随着女性年龄的增长,卵巢不仅在促排卵后产生的卵子数量减少,而且卵子质量也下降,主要表现为非整倍体增加,这需要进一步进行复杂的分析,以避免胚胎着床和妊娠过程中的并发症。尽管高龄产妇有多种选择(如使用捐赠卵子),但这并不是大多数患者的首选。除非女性在年轻时就冷冻了自己的卵子,否则生殖医学应尝试优化其使用自身卵子受孕的机会,只要成功的机会合理。衰老是由多种原因引起的,但端粒磨损是导致衰老的主要途径之一。有几项研究报告将端粒生物学与生殖联系起来,但导致中年时卵巢功能迅速衰退的分子原因仍难以捉摸。本文将重点介绍过去几年在生殖衰老的小鼠模型和卵巢功能衰竭的人类中获得的关于卵巢衰老和疾病的知识,以及端粒在这个过程中的作用。此外,本文还将讨论目前正在研究的干细胞疗法实现卵巢年轻化的最新成果,以及通过组织碎片化实现卵巢激活和产生卵子的尝试。