Ageing is accompanied by aneuploidy in mammalian eggs, which underlies common pregnancy failures in reproductively older females. This is consistent with gradual, ageing-related depletion of centromeric cohesion proteins leading to premature separation of sister chromatids. However, such progressive cohesion loss does not satisfactorily explain the sharp rise in egg aneuploidy near the end of female reproductive life. Here we show that F-actin helps to keep most sister chromatids together after centromeric cohesion has deteriorated in ageing mammalian eggs. By combining targeted protein degradation with advanced microscopy of chromosomal dynamics in eggs of young and aged females, we demonstrate that actin mitigates premature sister chromatid separation arising from centromeric cohesion loss by limiting microtubule-dependent chromatid disengagement. We propose that impairment of this function underlies ageing-related exponential rise in egg aneuploidy.

中文翻译：

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O-162 卵母细胞基因组完整性的新兴机制

衰老伴随着哺乳动物卵子的非整倍性，这是生殖年龄较大的女性常见妊娠失败的基础。这与衰老相关的着丝粒内聚蛋白逐渐耗尽导致姐妹染色单体过早分离是一致的。然而，这种进行性内聚力的丧失并不能令人满意地解释卵子非整倍体在接近雌性生殖生命末期时的急剧上升。在这里，我们展示了在衰老的哺乳动物卵子中着丝粒凝聚力恶化后，F-肌动蛋白有助于将大多数姐妹染色单体保持在一起。通过将靶向蛋白质降解与年轻和老年女性卵子中染色体动力学的先进显微镜相结合，我们证明肌动蛋白通过限制微管依赖性染色单体脱离来减轻由着丝粒内聚力丧失引起的过早姐妹染色单体分离。我们提出这一功能的损害是与衰老相关的卵子非整倍性指数上升的基础。