Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.

Authors

Tom Lemonnier, Marie Dumont, Jiyeon Leem, Aysia Khan, Hossein Yazdkhasti, Vitaly Zimyanin, Ani Khutsaidze, Stefanie Redemann, Daniele Fachinetti, Binyam Mogessie

Published in

The Journal of cell biology. Volume 225. Issue 11. Nov 02, 2026. Epub Oct 19, 2026.

Abstract

Maternal age is the primary risk factor for aneuploidy in mammalian oocytes, but the molecular mechanisms that preserve meiotic chromosome segregation fidelity during aging remain incompletely understood. Using ultrastructural analysis, we observe that spindle microtubules in aged mouse oocytes tend to exhibit increased misorientation and shorter interaction lengths, whereas microtubule number and density remain largely unchanged. We demonstrate that the levels of the key centromeric components CENP-A and CENP-C are reduced in oocytes from aged mice. Acute degradation of CENP-A during meiosis I affects CENP-C stability at centromeres and causes chromosome segregation errors in young oocytes, a phenotype not observed in mitosis. The expression of exogenous CENP-C rescues these defects via CENP-B-dependent centromere binding, supporting a link between centromere weakening and meiotic errors. This intervention also partially improves chromosome alignment in oocytes from older animals. Together, these findings implicate centromere weakening, alongside cytoskeletal disorganization, in the age-related decline in chromosome segregation fidelity in oocytes.

PMID:
42895520
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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