Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Nat Rev Mol Cell Biol. 2023 Jan;24(1):27-44. doi: 10.1038/s41580-022-00517-3. Epub 2022 Sep 6.
During fertilization, the egg and the sperm are supposed to contribute precisely one copy of each chromosome to the embryo. However, human eggs frequently contain an incorrect number of chromosomes - a condition termed aneuploidy, which is much more prevalent in eggs than in either sperm or in most somatic cells. In turn, aneuploidy in eggs is a leading cause of infertility, miscarriage and congenital syndromes. Aneuploidy arises as a consequence of aberrant meiosis during egg development from its progenitor cell, the oocyte. In human oocytes, chromosomes often segregate incorrectly. Chromosome segregation errors increase in women from their mid-thirties, leading to even higher levels of aneuploidy in eggs from women of advanced maternal age, ultimately causing age-related infertility. Here, we cover the two main areas that contribute to aneuploidy: (1) factors that influence the fidelity of chromosome segregation in eggs of women from all ages and (2) factors that change in response to reproductive ageing. Recent discoveries reveal new error-causing pathways and present a framework for therapeutic strategies to extend the span of female fertility.
在受精过程中，卵子和精子应该各自向胚胎提供一套准确的染色体。然而，人类卵子经常含有错误数量的染色体——这种情况被称为非整倍体，它在卵子中比在精子或大多数体细胞中更为普遍。反过来，卵子中的非整倍体是不孕、流产和先天性综合征的主要原因。非整倍体是卵子从其前体细胞卵母细胞发育过程中减数分裂异常的结果。在人类卵母细胞中，染色体经常错误地分离。染色体分离错误在女性从 35 岁中期开始增加，导致高龄产妇卵子的非整倍体水平更高，最终导致与年龄相关的不孕。在这里，我们涵盖了导致非整倍体的两个主要方面：（1）影响所有年龄段女性卵子中染色体分离保真度的因素，以及（2）对生殖衰老做出反应的因素。最近的发现揭示了新的导致错误的途径，并为延长女性生育能力的治疗策略提供了一个框架。
