A previously unknown oocyte protein, OMC1, has been identified as a key factor in maintaining chromosome cohesion in eggs throughout the prolonged period of reproductive dormancy. The findings could provide new insights into age-related decline in oocyte quality and aneuploidy. Unlike sperm, which are continuously produced after puberty, female eggs are formed before birth and remain arrested in meiosis for years or decades until ovulation. During this prolonged dormant period, chromosome organization is maintained by the cohesin protein complex containing REC8, which acts as molecular glue to hold duplicated chromosome copies together. However, REC8 is not replenished during this period and progressively declines with age, contributing to chromosome-segregation errors and aneuploidy.
A study at Graduate School of Medicine, Chiba University, Japan, has now identified a previously uncharacterized protein that appears to help preserve REC8 cohesin in oocytes. Published in Nature Aging, the study identified the protein OMC1, encoded by the Omc1 gene, as a potential maintenance factor for chromosome cohesion during reproductive aging. The researchers initially compared gene-expression profiles of fetal oocytes with male germ cells using single-cell RNA sequencing. Combined with experiments involving mice with delayed meiotic progression, this analysis identified Omc1 as a gene specifically activated in oocytes shortly before they enter meiotic arrest. OMC1 was subsequently detected on oocyte chromosomes at sites overlapping with REC8 and was found to remain associated with chromosomes from the fetal stage through adulthood.
To determine its function, the researchers generated mice lacking Omc1. In these animals, REC8 cohesin was lost from chromosomes prematurely after oocytes entered the dormant state. Consequently, even young oocytes exhibited reduced chromosome cohesion and chromosome-segregation errors resembling those observed during normal reproductive aging. Restoring OMC1 in adult oocytes partially recovered chromosome-associated REC8 and reduced chromosome abnormalities. These findings indicate that OMC1 may actively preserve REC8 rather than simply preventing the general aging of the oocyte. According to Prof. Ishiguro, OMC1 may therefore be considered a maintenance factor that extends the chromosomal lifespan of eggs.
The study also provided a potential link between OMC1 function and human reproductive aging. Previous genetic studies have identified variants in CCDC201, the human counterpart of Omc1, in individuals with early menopause and impaired ovarian function. When the researchers tested a truncated mouse OMC1 protein corresponding to one such human variant, the protein failed to localize properly to oocyte chromosomes and was unable to restore chromosome cohesion. The findings suggest that defective OMC1/CCDC201 activity may influence the maintenance of chromosome integrity and contribute to differences in reproductive aging.
Age-related loss of chromosome cohesion is an important contributor to oocyte aneuploidy, which is associated with infertility, miscarriage and chromosomal disorders, including Down syndrome. The identification of OMC1 provides a new molecular perspective on how oocytes may preserve chromosome integrity over prolonged periods of meiotic arrest.
The researchers emphasize that OMC1 should not yet be viewed as a means of stopping ovarian aging. Rather, it appears to be part of a chromosome-maintenance system that helps preserve the integrity of the egg over time. Understanding this mechanism could eventually support approaches to assess or potentially mitigate age-related deterioration in oocyte quality, although clinical applications remain speculative and require substantial further investigation.
With increasing numbers of pregnancies occurring at older maternal ages, the findings highlight the importance of understanding the molecular mechanisms underlying reproductive aging. Further research will be needed to determine whether the OMC1/CCDC201 pathway can be safely targeted and whether preserving its function could ultimately influence human oocyte quality or reproductive outcomes.
References
- Iisaka S, Yoshida S, Shimada R, Mishina T, Fujimura S, Koshiguchi M, et al. Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life. Nat Aging. 2026. Published October 29, 2026.