The function of spindle checkpoint in mouse oocytes

抄録

Chromosome segregation errors are highly frequent in mammalian female meiosis and their incidence increases with maternal age. The fate of aneuploid eggs is dependent on stringency of mechanisms detecting unattached or repairing incorrectly attached kinetochores. In case of their failure, the newly forming embryo will inherit the impaired set of chromosomes, which has severe consequences for its further development. It was debated for long time whether SAC in oocytes is capable of arresting cell cycle progression in response to unaligned kinetochores. From what we know, it is clear that abolishing SAC is forcing oocytes to segregate their chromosomes randomly during precocious entry into anaphase. However, it was also reported that for the Anaphase Promoting Complex (APC) activation, which is a prerequisite to anaphase entry, alignment only of a critical mass of kinetochores on equatorial plane is sufficient. This indicates that the function of SAC in oocytes is different from somatic cells. To analyze this phenomenon we have used live cell confocal microscopy to monitor chromosome movements, spindle formation, APC activation and polar body extrusion (PBE) simultaneously in individual oocytes at various time points during first meiotic division. Our results are demonstrating that multiple unaligned kinetochores and severe congression defects are tolerated at metaphase to anaphase transition. This indicates that checkpoint mechanisms operating in oocytes at this point are essential for accurate timing of APC activation in meiosis I, but they are insufficient in detection or correction of unaligned chromosomes, preparing thus conditions for propagating the aneuploidy to the embryo.