BACKGROUND Meiotic chromosome segregation in human oocytes is notoriously error-prone, especially with ageing. Such errors markedly reduce the reproductive chances of increasing numbers of women embarking on pregnancy later in life. However, understanding the basis for these errors is hampered by limited access to human oocytes. OBJECTIVE AND RATIONALE Important new discoveries have arisen from molecular analyses of human female recombination and aneuploidy along with high-resolution analyses of human oocyte maturation and mouse models. Here, we review these findings to provide a contemporary picture of the key players choreographing chromosome segregation in mammalian oocytes and the cellular basis for errors. SEARCH METHODS A search of PubMed was conducted using keywords including meiosis, oocytes, recombination, cohesion, cohesin complex, chromosome segregation, kinetochores, spindle, aneuploidy, meiotic cell cycle, spindle assembly checkpoint, anaphase-promoting complex, DNA damage, telomeres, mitochondria, female ageing and female fertility. We extracted papers focusing on mouse and human oocytes that best aligned with the themes of this review and that reported transformative and novel discoveries. OUTCOMES Meiosis incorporates two sequential rounds of chromosome segregation executed by a spindle whose component microtubules bind chromosomes via kinetochores. Cohesion mediated by the cohesin complex holds chromosomes together and should be resolved at the appropriate time, in a specific step-wise manner and in conjunction with meiotically programmed kinetochore behaviour. In women, the stage is set for meiotic error even before birth when female-specific crossover maturation inefficiency leads to the formation of at-risk recombination patterns. In adult life, multiple co-conspiring factors interact with at-risk crossovers to increase the likelihood of mis-segregation. Available evidence support that these factors include, but are not limited to, cohesion deterioration, uncoordinated sister kinetochore behaviour, erroneous microtubule attachments, spindle instability and structural chromosomal defects that impact centromeres and telomeres. Data from mice indicate that cohesin and centromere-specific histones are long-lived proteins in oocytes. Since these proteins are pivotal for chromosome segregation, but lack any obvious renewal pathway, their deterioration with age provides an appealing explanation for at least some of the problems in older oocytes. WIDER IMPLICATIONS Research in the mouse model has identified a number of candidate genes and pathways that are important for chromosome segregation in this species. However, many of these have not yet been investigated in human oocytes so it is uncertain at this stage to what extent they apply to women. The challenge for the future involves applying emerging knowledge of female meiotic molecular regulation towards improving clinical fertility management.

中文翻译：

---

卵母细胞染色体分离的调节和女性减数分裂错误的细胞基础。

背景技术人类卵母细胞中的减数分裂染色体分离是出了名的容易出错，尤其是随着年龄的增长。这些错误显着降低了越来越多的女性在晚年开始怀孕的生育机会。然而，了解这些错误的基础受到对人类卵母细胞的有限访问的阻碍。目标和基本原理 重要的新发现来自人类女性重组和非整倍体的分子分析以及人类卵母细胞成熟和小鼠模型的高分辨率分析。在这里，我们回顾了这些发现，以提供当代设计哺乳动物卵母细胞染色体分离的关键参与者和错误的细胞基础。搜索方法 使用包括减数分裂、卵母细胞、重组、凝聚、凝聚素复合物、染色体分离、动粒、纺锤体、非整倍体、减数分裂细胞周期、纺锤体组装检查点、后期促进复合物、DNA 损伤、端粒、线粒体、女性衰老和女性生育能力。我们提取了重点关注小鼠和人类卵母细胞的论文，这些论文最符合本综述的主题，并报告了变革性和新颖的发现。结果 减数分裂包含两轮连续的染色体分离，由纺锤体执行，纺锤体的组成微管通过动粒结合染色体。由内聚素复合物介导的内聚力将染色体保持在一起，应该在适当的时间以特定的逐步方式并结合减数分裂程序的动粒行为来解决。在女性中，甚至在出生前，当女性特异性交叉成熟效率低下导致风险重组模式的形成时，这个阶段就已经为减数分裂错误做好了准备。在成年生活中，多种共谋因素与有风险的交叉相互作用，以增加错误分离的可能性。现有证据支持这些因素包括但不限于内聚力退化、不协调的姐妹动粒行为、错误的微管附着、纺锤体不稳定性和影响着丝粒和端粒的结构染色体缺陷。来自小鼠的数据表明，cohesin 和着丝粒特异性组蛋白是卵母细胞中的长寿命蛋白质。由于这些蛋白质对染色体分离至关重要，但缺乏任何明显的更新途径，它们随着年龄的增长而恶化，至少为老年卵母细胞的一些问题提供了一个有吸引力的解释。更广泛的影响 对小鼠模型的研究已经确定了许多对该物种染色体分离很重要的候选基因和途径。然而，其中许多尚未在人类卵母细胞中进行研究，因此现阶段尚不确定它们在多大程度上适用于女性。未来的挑战包括将新兴的女性减数分裂分子调控知识应用于改善临床生育管理。其中许多尚未在人类卵母细胞中进行研究，因此现阶段尚不确定它们在多大程度上适用于女性。未来的挑战包括将新兴的女性减数分裂分子调控知识应用于改善临床生育管理。其中许多尚未在人类卵母细胞中进行研究，因此现阶段尚不确定它们在多大程度上适用于女性。未来的挑战包括将新兴的女性减数分裂分子调控知识应用于改善临床生育管理。