Actin limits egg aneuploidies associated with female reproductive aging.

Abstract

Aging-related centromeric cohesion loss underlies premature separation of sister chromatids (PSSC) and egg aneuploidy in reproductively older females. Here we show that F-actin maintains chromatid association after cohesion deterioration in aged eggs. F-actin disruption in aged mouse eggs exacerbated PSSC, while its removal in young eggs induced extensive chromatid separation events generally only seen in advanced reproductive ages. In young eggs containing experimentally reduced cohesion, F-actin removal accelerated PSSC in a microtubule dynamics-dependent manner, suggesting that actin counteracts chromatid-pulling spindle forces. Consistently, F-actin stabilization restricted PSSC even when cohesion was acutely depleted by targeted protein degradation. We conclude that actin mitigates PSSCs arising from age-related cohesion depletion by limiting microtubule-driven chromatid separation. This is supported by a spindle-specific disruption of F-actin in aged mammalian eggs. One-Sentence SummaryActin counteracts microtubule-based pulling forces to reduce the effects of chromosome cohesion loss in aged mammalian eggs.