Clinica Valle Giulia, G.EN.E.R.A. Center for Reproductive Medicine, via G. De Notaris 2b, 00197 Rome, Italy.
GENETYX, molecular biology laboratory, via Fermi 1, 36063 Marostica (VI), Italy.
Hum Reprod Update. 2017 Nov 1;23(6):706-722. doi: 10.1093/humupd/dmx026.
The unbalanced transmission of chromosomes in human gametes and early preimplantation embryos causes aneuploidy, which is a major cause of infertility and pregnancy failure. A baseline of 20% of human oocytes are estimated to be aneuploid and this increases exponentially from 30 to 35 years, reaching on average 80% by 42 years. As a result, reproductive senescence in human females is predominantly determined by the accelerated decline in genetic quality of oocytes from 30 years of age.
Understanding mechanisms of chromosome segregation and aneuploidies in the female germline is a crucial step towards the development of new diagnostic approaches and, possibly, for the development of therapeutic targets and molecules. Here, we have reviewed emerging mechanisms that may drive human aneuploidy, in particular the maternal age effect.
We conducted a systematic search in PubMed Central of the primary literature from 1990 through 2016 following the PRISMA guidelines, using MeSH terms related to human aneuploidy. For model organism research, we conducted a literature review based on references in human oocytes manuscripts and general reviews related to chromosome segregation in meiosis and mitosis.
Advances in genomic and imaging technologies are allowing unprecedented insight into chromosome segregation in human oocytes. This includes the identification of a novel chromosome segregation error, termed reverse segregation, as well as sister kinetochore configurations that were not predicted based on murine models.
Elucidation of mechanisms that result in errors in chromosome segregation in meiosis may lead to therapeutic developments that could improve reproductive outcomes by reducing aneuploidy.
人类配子和早期胚胎中染色体的不平衡传递导致非整倍体，这是非不孕和妊娠失败的主要原因。据估计，有 20%的人类卵子存在非整倍体，从 30 岁到 35 岁呈指数增长，到 42 岁时平均达到 80%。因此，女性生殖衰老主要取决于 30 岁以后卵母细胞遗传质量的加速下降。
了解染色体分离和女性生殖系非整倍体的机制是开发新的诊断方法的关键步骤，并且可能是开发治疗靶点和分子的关键步骤。在这里，我们综述了可能导致人类非整倍体的新出现的机制，特别是母体年龄效应。
我们按照 PRISMA 指南，在 PubMed Central 中使用与人类非整倍体相关的 MeSH 术语，对 1990 年至 2016 年的主要文献进行了系统搜索。对于模式生物研究，我们根据人类卵母细胞文献中的参考文献以及与减数分裂和有丝分裂中的染色体分离相关的一般综述进行了文献综述。
基因组和成像技术的进步使我们能够以前所未有的方式深入了解人类卵母细胞中的染色体分离。这包括鉴定一种新的染色体分离错误，称为反向分离，以及基于鼠模型未预测到的姐妹动粒构型。
阐明导致减数分裂中染色体分离错误的机制可能会导致治疗方法的发展，通过减少非整倍体来改善生殖结局。
