Reduced ability to recover from spindle disruption and loss of kinetochore spindle assembly checkpoint proteins in oocytes from aged mice.
Currently, maternal aging in women, based on mouse models, is thought to raise oocyte aneuploidy rates, because chromosome cohesion deteriorates during prophase arrest, and Sgo2, a protector of centromeric cohesion, is lost. Here we show that the most common mouse strain, C57Bl6/J, is resistant to maternal aging, showing little increase in aneuploidy or Sgo2 loss. Instead it demonstrates significant kinetochore-associated loss in the spindle assembly checkpoint protein Mad2 and phosphorylated Aurora C, which is involved in microtubule-kinetochore error correction. Their loss affects the fidelity of bivalent segregation but only when spindle organization is impaired during oocyte maturation. These findings have an impact clinically regarding the handling of human oocytes ex vivo during assisted reproductive techniques and suggest there is a genetic basis to aneuploidy susceptibility.
School of Biomedical Sciences & Pharmacy; University of Newcastle; Callaghan, NSW, Australia.
Yan
Y
Yun
School of Biomedical Sciences & Pharmacy; University of Newcastle; Callaghan, NSW, Australia.
Janet E
JE
Holt
School of Biomedical Sciences & Pharmacy; University of Newcastle; Callaghan, NSW, Australia; Centre for Biological Sciences; Faculty of Natural and Environmental Sciences; University of Southampton; Southampton, UK.
Simon I R
SI
Lane
School of Environmental and Life Sciences; University of Newcastle; Callaghan, NSW, Australia.
Eileen A
EA
McLaughlin
School of Biomedical Sciences & Pharmacy; University of Newcastle; Callaghan, NSW, Australia; Centre for Biological Sciences; Faculty of Natural and Environmental Sciences; University of Southampton; Southampton, UK.
Julie A
JA
Merriman
School of Biomedical Sciences & Pharmacy; University of Newcastle; Callaghan, NSW, Australia; Centre for Biological Sciences; Faculty of Natural and Environmental Sciences; University of Southampton; Southampton, UK.
Keith T
KT
Jones
D000375:Aging / Q000378:metabolism*; D000782:Aneuploidy; D000818:Animals; D064108:Aurora Kinase C / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D005260:Female; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D064246:Mad2 Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015739:Nocodazole / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity; D008941:Spindle Apparatus / Q000378:metabolism*
D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C532340:SGOL2 protein, mouse; D064108:Aurora Kinase C; D015739:Nocodazole
aging; aneuploidy; cell cycle; error correction; meiosis; oocyte; spindle assembly checkpoint