Eggs follow a very different developmental path from sperm. Once a male hits puberty, sperm cells are produced continuously throughout his life. Eggs, however, are all produced during the fetal stage. Once formed, eggs enter a long dormant state called the dictyate stage, in which the process of cell division (meiosis) is paused partway through. This dormant period ends only when the egg is ovulated. During this time, the egg keeps its chromosomes properly organized due to the presence of a protein complex called REC8 cohesin. Working like a molecular glue, REC8 holds together the chromosome copies created before the cell division arrest.
Interestingly, REC8 is never replenished during the dormant period. Because REC8 cohesin weakens progressively with age, its decline is now thought to be a major reason why eggs from older women are more likely to end up with the wrong number of chromosomes. This condition, called aneuploidy, is a leading cause of miscarriage, infertility, and chromosomal disorders such as Down syndrome. It remains unclear whether egg cells have any active mechanism to protect this irreplaceable cohesin from breaking down, or whether the protein is simply left to degrade passively over time as the egg ages.
In a recent study, a research team led by Professor Kei-ichiro Ishiguro from the Graduate School of Medicine, Chiba University , Japan, set out to address this question. Their paper, which was published in the journal Nature Aging on October 29, 2026, describes the discovery of a previously unknown protein that helps preserve chromosome cohesion in eggs from before birth to adulthood. Co-authors of the study included Sakie Iisaka, a Ph D student, and Dr. Ryuki Shimada from Chiba University, as well as Dr. Tomoya S. Kitajima and Dr. Shuhei Yoshida from the RIKEN Center for Biosystems Dynamics Research (BDR), Japan.
The researchers first compared gene activity in fetal immature eggs (oocytes) and male germ cells, which do not undergo the same prolonged arrest, using single-cell RNA sequencing. This comparison, combined with data from mice with delayed meiosis, led them to identify a previously uncharacterized gene that is active specifically in oocytes shortly before they enter the dormant stage. The team named this gene Omc1 and its protein OMC1 for Oocyte-specific Meiotic Chromosome protein 1. Further experiments showed that OMC1 is present on chromosomes of the egg in the same locations as REC8 cohesin and remains there from the fetal stage throughout adulthood.
To investigate the function of OMC1, the team engineered mice lacking Omc1. Once eggs produced by these mice entered their long dormant period, REC8 cohesin began disappearing from chromosomes earlier than normal. As a result, even young eggs from these mice showed weakened chromosome cohesion and errors in chromosome separation similar to those frequently seen in aged eggs.
Notably, when the researchers restored OMC1 in adult oocytes, REC8 levels on chromosomes partly recovered and chromosome errors decreased, suggesting that OMC1 actively works to keep REC8 in place. "Based on these results, OMC1 should be regarded not as a factor that stops aging itself, but as a maintenance factor that extends the chromosomal lifespan of eggs," remarks Prof. Ishiguro.
Previous genetic studies have identified variants in the human OMC1 counterpart, CCDC201, that are associated with early menopause and loss of ovarian function. To explore the potential functional impact of such variants, the team tested a truncated mouse OMC1 protein corresponding to one of the human CCDC201 variants. The truncated protein failed to localize to oocyte chromosomes and could not restore chromosome cohesion. These findings suggest that impaired OMC1/CCDC201 function may contribute to variation in reproductive aging.
Overall, this study provides valuable insights into how oocytes maintain their chromosomes, with important implications for reproductive health in societies where the average age at childbirth is increasing. "We believe that revealing part of the mechanism that protects chromosome cohesion from age-related decline is highly significant in modern society, where people are increasingly having children later in life," concludes Prof. Ishiguro. "In the longer term, these findings may contribute to the development of approaches for understanding, assessing, or potentially mitigating the age-related decline in egg quality."
Within the next decade, scientists may be able to find safe ways to preserve or supplement OMC1 function before cohesin is irreversibly lost, establishing a new foundation for strategies aimed at maintaining oocyte quality and extending fertility.
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About Professor Kei-ichiro Ishiguro
Dr. Kei-ichiro Ishiguro obtained a PhD in Biophysics and Biochemistry from the University of Tokyo, Japan, in 2000. He currently serves as Professor at the Graduate School of Medicine, Chiba University. His research focuses on meiosis, chromosome dynamics, the cell cycle, and germ and stem cells. He has published over 100 peer-reviewed studies on these topics. He has authored over 53 indexed publications in the fields of chromosome biology and reproductive cell development. He has been affiliated with multiple academic societies such as The Society for Reproduction and Development, The Japanese Society for Epigenetics, and The Genetics Society of Japan.
Funding:
This work was supported in part by JSPS KAKENHI grant number JP22K15039 to Ryuki Shimada; RIKEN intramural grants, RIKEN Pioneering Project "Long-Timescale Molecular Chronobiology", JSPS KAKENHI 25H00981/23H04948/21H02407, and Naito Foundation Research Grant to Tomoya S. Kitajima; MEXT/JSPS KAKENHI grants JP22K19315, JP23H00379, JP24H02050, JP25H01297, 25H01304, JP22H04922 AdAMS to Kei-ichiro Ishiguro; Grant from AMED PRIME (21gm6310021h0003) to Kei-ichiro Ishiguro; Grants from The Mitsubishi Foundation; The Naito Foundation; Astellas Foundation for Research on Metabolic Disorders; The Uehara Memorial Foundation; Takeda Science Foundation to Kei-ichiro Ishiguro.
Reference:
Title of original paper: Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life
Authors: Sakie Iisaka1,2, Shuhei Yoshida3, Ryuki Shimada1,2, Tappei Mishina4, Sayoko Fujimura5, Manami Koshiguchi3, Ryuichi Kimura6, Shinya Oki6, Kimi Araki7, Tomoya S. Kitajima3, and Kei-ichiro Ishiguro1,2,8
Affiliations: (1) Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University; (2) Department of Biomedical Science, Graduate School of Medicine, Chiba University; (3) Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR); (4) Faculty of Agriculture, Kyushu University; (5) Liaison Laboratory Research Promotion Center, IMEG, Kumamoto University; (6) Institute of Resource Development and Analysis, Kumamoto University; (7) Institute of Resource Development and Analysis & Center for Metabolic Regulation of Healthy Aging, Kumamoto University; (8) Next Generation In Vivo Research Exploratory Center (cNIVR), Chiba University
Journal: Nature Aging
DOI: https://doi.org/10.1038/s43587-026-01245-5
