Understanding and preventing age-associated chromosome segregation errors in oocytes

Tomoya Kitajima

RIKEN Center for Biosystems Dynamics Research, Kobe, JAPAN

Egg aneuploidy is a leading cause of miscarriage and congenital disorders such as Down syndrome. It arises from chromosome segregation errors during oocyte meiosis, with incidence increasing markedly with maternal age. However, the oocyte-intrinsic features and age-associated defects that promote these errors remain incompletely understood.

Using mouse oocytes as a model, we investigate chromosome dynamics and the cellular machinery driving meiotic chromosome segregation, including the spindle and kinetochores. We have identified multiple oocyte-intrinsic factors that predispose oocytes to segregation errors, including (1) mechanisms governing spindle bipolarization and (2) regulation of kinetochore–microtubule attachments. In addition, we have found that (3) premature chromosome separation represents a major age-associated defect. In this talk, I will present our recent findings on the cell biological basis of chromosome segregation errors in oocytes and discuss emerging error-prevention strategies using synthetic tools currently under development.

Kyogoku H, Tarama M, Matsuwaka M, Mishina T, Harada A, Nakagawa R, Kumon M, Shimizu Y, Ohkawa Y, Shibata T, Inoue A, Kitajima TS
Cytoplasmic competition between separate parental pronuclei in zygotes
Nature (2026) doi:10.1038/s41586-026-10417-7.

Zhou Y, Asai K, Kyogoku H, Kitajima TS.
Designing protein-based artificial kinetochores as decoys to prevent meiotic errors in oocytes.
Nature Cell Biology 27(11), 2007-2018(2025) doi: 10.1038/s41556-025-01792-w.

Yoshida S, Nakagawa R, Asai K, Kitajima TS.
MPS1 promotes timely spindle bipolarization to prevent kinetochore-microtubule attachment errors in oocytes .
The EMBO Journal 44(13), 3794-3823(2025) doi: 10.1038/s44318-025-00461-w.

Asai K, Zhou Y, Takenouchi O, Kitajima TS.
Artificial kinetochore beads establish a biorientation-like state in the spindle.
Science 385(6715), 1366-1375 (2024) doi: 10.1126/science.adn5428.

Takenouchi O, Sakakibara Y, Kitajima TS.
Live chromosome identifying and tracking reveals size-based spatial pathway of meiotic errors in oocytes.
Science 385(6706), eadn5529 (2024) doi: 10.1126/science.adn5529.