2026-10-23 イェール大学
Super-resolution image of the intricate chromosome division machinery in a young mouse oocyte. At metaphase I, homologous chromosomes (green) are positioned within the spindle’s network of microtubules (orange). Centromeres (magenta) mark the sites where chromosomes connect to this machinery, helping ensure that the egg receives the correct number of chromosomes.Image courtesy of Binyam Mogessie
＜関連情報＞
- https://news.yale.edu/2026/10/23/new-study-reveals-how-egg-quality-declines-reproductive-age
- https://rupress.org/jcb/article/225/11/e202606132/283083/Declining-centromere-strength-compromises-meiotic
加齢卵母細胞におけるセントロメア強度の低下は、減数分裂時の染色体分離を損なう
Declining centromere strength compromises meiotic chromosome segregation in aging oocytes
Tom Lemonnier , Marie Dumont , Jiyeon Leem , Aysia Khan , Hossein Yazdkhasti , Vitaly Zimyanin , Ani Khutsaidze, Stefanie Redemann , Daniele Fachinetti , Binyam Mogessie
Journal of Cell Biology Publised:October 19 2026
DOI:https://doi.org/10.1083/jcb.202606132
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.
