Aneuploidy (having an abnormal number of chromosomes) is a common defect in embryos and often leads to their developmental arrest. Most research has focused on meiotic errors during gametogenesis, but chromosome segregation errors are equally likely to arise during the first zygotic mitotic cleavages. Now, Shawn Chavez and colleagues use bovine embryos to dissect the molecular origins of aneuploidy during early cleavage divisions. The researchers find that 37.7% of embryos contain micronuclei, which are encapsulated chromosomes that failed to segregate properly during cell division. Most of the micronuclei arise during bipolar divisions and subsequently undergo unilateral inheritance or fuse back with the primary nucleus. In contrast, multipolar divisions often give rise to cells that are uniparental following failed fusion of the parental nuclei. By sequencing individual blastomeres, they find that only 16% of embryos are fully euploid and the rest are aneuploid or mosaic. In BUB1B-depleted embryos, which lack a serine/threonine kinase component of the mitotic checkpoint complex (MCC), most blastomeres display aneuploidy, while other checkpoint protein kinases are downregulated. This demonstrates an important role for MCC in ensuring chromosome fidelity. Collectively, these data provide new insight into the relationship between checkpoints, cell division and aneuploidy in bovine embryos, which display many common characteristics with human embryos.
A new look at aneuploidy
A new look at aneuploidy. Development 1 April 2022; 149 (7): e149_e0704. doi:
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