How eggs protect chromosome connections during prolonged dormancy

How eggs protect chromosome connections during prolonged dormancy Sadie Harley Scientific Editor Robert Egan Senior Editor 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. 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. Searching for an egg maintenance protein 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, 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 doctoral 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. Missing OMC1 accelerates chromosome errors 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. 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," said Ishiguro. Links to reproductive aging in humans 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 insights into how oocytes maintain their chromosomes, with 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 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. Publication details Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life, Nature Aging (2026). DOI: 10.1038/s43587-026-01245-5 Journal information: Nature Aging Provided by Chiba University