Kinetochore deterioration concommitant with centromere weakening during aging in mouse oocyte meiosis-I.


Journal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484

Informations de publication

Date de publication:
05 2023
Historique:
revised: 18 03 2023
received: 11 01 2023
accepted: 03 04 2023
medline: 21 4 2023
pubmed: 20 4 2023
entrez: 20 04 2023
Statut: ppublish

Résumé

Age-related oocyte aneuploidy occurs as a result of chromosome segregation errors in female meiosis-I and meiosis-II, and is caused by a progressive age-related deterioration of the chromosome segregation machinery. Here, we assess the impact of age upon the kinetochore, the multi-protein structure that forms the link between the chromosome and spindle microtubules. We find that in meiosis-I the outer kinetochore assembles at germinal vesicle breakdown, but that a substantially smaller outer kinetochore is assembled in oocytes from aged mice. We show this correlates with a weaker centromere in aged oocytes and, using nuclear transfer approaches to generate young-aged hybrid oocytes, we show that outer kinetochore assembly always mirrors the status of the centromere, regardless of cytoplasmic age. Finally, we show that weaker kinetochores in aged oocytes are associated with thinner microtubule bundles, that are more likely to be mis-attached. We conclude that progressive loss of the centromere with advancing maternal age underpins a loss of the outer kinetochore in meiosis-I, which likely contributes to chromosome segregation fallibility in oocytes from older females.

Identifiants

pubmed: 37078553
doi: 10.1096/fj.202300062R
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e22922

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

© 2023 Federation of American Societies for Experimental Biology.

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Auteurs

Lin Yin (L)

College of Animal Science and Technology, Northwest A&F University, Yangling, PR China.
Centre de recherche du Centre Hospitalier de I'Université de Montréal (CRCHUM), Montréal, Québec, Canada.

Aleksandar I Mihajlović (AI)

Centre de recherche du Centre Hospitalier de I'Université de Montréal (CRCHUM), Montréal, Québec, Canada.

Gongshe Yang (G)

College of Animal Science and Technology, Northwest A&F University, Yangling, PR China.

Greg FitzHarris (G)

Centre de recherche du Centre Hospitalier de I'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
Department of Obstetrics and Gynaecology, Université de Montréal, Montréal, Québec, Canada.

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