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How does p53 mediate apoptosis of aneuploid cells in embryos?
Aneuploid cells elicit several cellular stress responses [Santaguida S. and Amon A. (2015)]
Aneuploidy
Oxidative Proteotoxicity Metabolic Genomic Stress kinase stress alterations Instability p38 activation
• Aneuploidy disrupts cellular redox homeostasis leading to accumulation of intracellular reactive oxygen species [Dephoure N., et al. (2014)]
• Excess of proteins produced by additional chromosomes disturbs the protein homeostasis in aneuploid cells
[Oromendia A. B., et al. (2012); Ohashi, A. et al., (2015)]
• Aneuploid cells display altered metabolic properties such as perturbations in amino acid metabolism
[Williams B. R., et al. (2008)]
• Chromosome mis-segregation can cause DNA damage [Ohashi, A. et al., (2015)]
• Aneuploidy can generate a p38 kinase–dependent stress response to delay cell cycle progression
[Thompson S. L. and Compton D. A. (2010)]
Increased protein misfolding in aneuploid cells
Members of the Heat shock protein70 (HSP70) family of molecular chaperones function in alleviating misfolded protein stress
Diploid Aneuploid
DAPI/DIC HSP70 DAPI/DIC HSP70
+/- Reversine
4 3 2 1 0
**
Diploid Aneuploid
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PRECONGRESS COURSE 10 I VIENNA, AUSTRIA – 23 JUNE 2019 37
Late Early
blastocyst blastocyst Morula Late 8 cell
Relative HSP70 intensity in EPI