Spindle assembly checkpoint insensitivity allows meiosis-II despite chromosomal defects in aged eggs.
EMBO Rep
; 24(11): e57227, 2023 11 06.
Article
em En
| MEDLINE
| ID: mdl-37795949
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Pontos de Checagem da Fase M do Ciclo Celular
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Fuso Acromático
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article