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O-162 Emerging mechanisms of oocyte genome integrity


 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.