Y chromosome instability in the early mouse embryo

The Y chromosome lacks canonical centromeric repeats necessary for high-fidelity chromosome segregation. In adult tissues, this causes Y loss and predisposes to disease. However, its impact on embryogenesis is unknown. Here, we identify the first mouse embryonic mitoses as a window during which the Y centromere is unusually weak. This vulnerability impairs kinetochore strength and the Y becomes preferentially trapped at the spindle pole, resulting in missegregation. To study the impact of Y loss, we generate an aggregation model to track specific aneuploidies in mosaic embryos. Loss of the Y slows down cell division and compromises embryo size. Our findings reveal a developmental window during which the Y is especially vulnerable to loss, with implications for male sex determination and the origin of Turner syndrome (XO).