2025-11-03 イェール大学
Web要約 の発言:
<関連情報>
- https://news.yale.edu/2025/11/03/new-tool-understanding-chromosome-abnormalities-eggs-older-women
- https://www.nature.com/articles/s43587-025-00997-w
多目的凝集操作システムにより、女性の生殖年齢に関連した卵子の異数性を調べる A versatile cohesion manipulation system probes female reproductive age-related egg aneuploidy
Jiyeon Leem,Tom Lemonnier,Ani Khutsaidze,Lei Tian,Xiaojun Xing,Suxia Bai,Timothy Nottoli & Binyam Mogessie
Nature Aging Published:03 November 2025
DOI:https://doi.org/10.1038/s43587-025-00997-w
Abstract
Female reproductive aging is accompanied by a sharp increase in egg aneuploidy rates. Premature loss of chromosome cohesion proteins and early separation of chromosomes are thought to cause high aneuploidy rates during maternal aging. However, because cohesion loss occurs gradually throughout a woman’s reproductive lifespan, and because cytoskeletal defects alone can lead to chromosomal abnormalities, the main causes of the rapid rise in aneuploidy at older reproductive ages are still unclear. In this study, we created a versatile and tunable cohesion manipulation system that enables rapid, dose-dependent degradation of the meiotic cohesin REC8 in live mouse oocytes. By coupling this system with quantitative high-resolution live imaging, we directly observed cohesion protein behavior during meiosis and tested the longstanding threshold model of aneuploidy development. Our results show that premature sister chromatid separation sharply increases only when REC8 levels drop below a critical threshold, supporting the idea of a nonlinear, vulnerability-triggering cohesion limit. We also used our system to examine how other age-related issues, such as cytoskeletal disruption and partial centromere dysfunction, can exacerbate chromatid separation in the context of weakened cohesion. This work provides a tractable oocyte platform for modeling and dissecting the multifactorial mechanisms driving female reproductive age-related egg aneuploidy.
