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Peer-reviewedCC BYThe Journal of cell biology

Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.

  • Tom Lemonnier1
  • Marie Dumont2
  • Jiyeon Leem1
  • Aysia Khan3,4,5
  • Hossein Yazdkhasti3,4,5
  • Vitaly Zimyanin3,4,5
  • Ani Khutsaidze1
  • Stefanie Redemann3,4,5
  • Daniele Fachinetti2
  • Binyam Mogessie1,6,7
7 affiliations
  1. 1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
  2. 2Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR144 & 3664 , Paris, France.
  3. 3Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  4. 4Center for Membrane and Cell Physiology, University of Virginia School of Medicine , Charlottesville, VA, USA.
  5. 5Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  6. 6Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
  7. 7Yale Center for Research on Aging, Yale School of Medicine , New Haven, CT, USA.
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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.

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Cite

BibTeXRIS
BibTeX
@article{lemonnier2026declining,
  title = {{Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.}},
  author = {Tom Lemonnier and Marie Dumont and Jiyeon Leem and Aysia Khan and Hossein Yazdkhasti and Vitaly Zimyanin and Ani Khutsaidze and Stefanie Redemann and Daniele Fachinetti and Binyam Mogessie},
  journal = {The Journal of cell biology},
  year = {2026},
  month = oct,
  doi = {10.1083/jcb.202606132},
  url = {https://europepmc.org/article/MED/42895520},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.
AU  - Tom Lemonnier
AU  - Marie Dumont
AU  - Jiyeon Leem
AU  - Aysia Khan
AU  - Hossein Yazdkhasti
AU  - Vitaly Zimyanin
AU  - Ani Khutsaidze
AU  - Stefanie Redemann
AU  - Daniele Fachinetti
AU  - Binyam Mogessie
PY  - 2026
DA  - 2026/10/19
JO  - The Journal of cell biology
DO  - 10.1083/jcb.202606132
UR  - https://europepmc.org/article/MED/42895520
AB  - 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.
SN  - 0021-9525
SN  - 1540-8140
ER  -