Fig. 8: Model for the elimination of aneuploid cells in the mouse embryo.

a Aneuploid cells generated at the four- to eight-cell stage are progressively depleted from the epiblast of the mosaic embryo from the early blastocyst stage to the early post-implantation via apoptosis. Diploid cells in the same embryo over-proliferate to compensate for the reduction in overall epiblast cell number thereby allowing for successful development. b In a normal (diploid) cell, cellular protein quality control mechanisms, involving the proteasome machinery and autophagy, degrade misfolded/unfolded proteins to prevent cytotoxicity and promote healthy cell survival²⁶. We hypothesise that in an aneuploid cell in the epiblast, gene aberrations are translated into protein aberrations. Chronic protein misfolding after several mitotic divisions upregulates autophagy to an extent where instead of protecting the cell, it mediates cell death. This prevents the aneuploid cell from continuing further in the development of the epiblast.