Spindle assembly checkpoint insensitivity allows meiosis-II despite chromosomal defects in aged eggs.
KIF18A
ageing
aneuploidy
oocyte meiosis
spindle assembly checkpoint
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 11 2023
06 11 2023
Historique:
revised:
07
09
2023
received:
22
03
2023
accepted:
19
09
2023
pmc-release:
05
10
2024
medline:
7
11
2023
pubmed:
5
10
2023
entrez:
5
10
2023
Statut:
ppublish
Résumé
Chromosome segregation errors in mammalian oocyte meiosis lead to developmentally compromised aneuploid embryos and become more common with advancing maternal age. Known contributors include age-related chromosome cohesion loss and spindle assembly checkpoint (SAC) fallibility in meiosis-I. But how effective the SAC is in meiosis-II and how this might contribute to age-related aneuploidy is unknown. Here, we developed genetic and pharmacological approaches to directly address the function of the SAC in meiosis-II. We show that the SAC is insensitive in meiosis-II oocytes and that as a result misaligned chromosomes are randomly segregated. Whilst SAC ineffectiveness in meiosis-II is not age-related, it becomes most prejudicial in oocytes from older females because chromosomes that prematurely separate by age-related cohesion loss become misaligned in meiosis-II. We show that in the absence of a robust SAC in meiosis-II these age-related misaligned chromatids are missegregated and lead to aneuploidy. Our data demonstrate that the SAC fails to prevent cell division in the presence of misaligned chromosomes in oocyte meiosis-II, which explains how age-related cohesion loss can give rise to aneuploid embryos.
Identifiants
pubmed: 37795949
doi: 10.15252/embr.202357227
pmc: PMC10626445
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57227Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2023 The Authors.
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