Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life

Abstract

In mammals, oocytes initiate meiosis during fetal development and then enter a prolonged meiotic arrest. During this female-specific long-term arrest, chromosome cohesion mediated by nonrenewable REC8 cohesin gradually deteriorates, predisposing oocytes to age-associated chromosome segregation errors when meiosis resumes for maturation in adulthood. Female-specific factors that counteract this deterioration remain unknown. Here we identify OMC1 as an oocyte-specific chromosomal protein required for the maintenance of chromosome cohesion through reproductive life. OMC1 associates with REC8-cohesin-containing chromosome axes from fetal stages through adult meiotic maturation. Using Omc1 knockout mice, we show that OMC1 is required for cohesin maintenance until completion of meiotic maturation, thereby suppressing age-associated chromosome segregation errors. These findings provide insight into the female germ-cell-intrinsic molecular basis that supports reproductive longevity by suppressing age-associated chromosome cohesion loss, which leads to egg aneuploidy, a major cause of infertility and congenital disorders. Mammalian oocytes undergo prolonged meiotic arrest during which sister chromatids are linked by cohesin complexes. Cohesion deterioration during aging results in aneuploidy. Here, Iisaka, Yoshida et al. identify OMC1 as an oocyte-specific protein that preserves chromosome cohesion throughout reproductive life. The loss of OMC1 accelerates age-related aneuploidy.

The authors' abstract, as published at the source. Nature Aging, 2026 · DOI ↗