For decades, biology textbooks have described ovaries as passive vaults of eggs. It gradually depletes with age until menopause. But a new study paints a far more dynamic picture: ovaries appear to monitor their egg supply actively, awakening a fixed fraction of eggs at any age.
Researchers at the Center for Genomic Regulation (CRG) in Barcelona built the first complete three-dimensional map of how a mammalian ovary changes across its lifespan. By combining high-resolution microscopy with artificial intelligence, they tracked more than 85,000 egg cells (oocytes) in over 100 intact mouse ovaries. The result is a dataset of unprecedented scale and precision, and a series of discoveries that overturn long-held assumptions.
As mice age, their total egg reserve collapses about tenfold. Yet the proportion of eggs in the critical transition from dormancy to growth stays steady at 14%.
“The same percentage of oocytes are being activated regardless of how old the mouse is. That means the ovary has a sensing mechanism which knows how many oocytes are in there and only awakens a fixed proportion. No one has ever known that before. It is completely new biology,” said Dr. Elvan Böke, senior author of the study.
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This suggests the ovary isn’t just a storage organ; it may be counting its eggs, possibly through a hormone or neuronal signal that scientists have yet to identify.
Another surprise: genetically identical mice raised in the same conditions ended up with wildly different ovarian reserves. By puberty, one mouse could have three times as many eggs as another.
“These mice are essentially identical twins of the same age with the same living conditions yet have completely different ovaries. We found huge variability, and it’s not genetic. It means there’s something else going on that we don’t understand yet,” said Böke.
This variability appears early in life, perhaps during embryonic development, and shapes ovarian function for the rest of the animal’s lifespan.
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For years, scientists suspected that densely packed dormant eggs might suppress one another, limiting activation. The CRG team found the opposite: areas with the highest density of dormant eggs were also the most active in awakening new ones.
“This idea has always floated around, but this is the first time there’s actual data,” said Arturo D’Angelo, first author of the study.
The researchers also discovered a developmental checkpoint: many follicles pause at around 60 micrometers in diameter, just before becoming hormonally responsive. Understanding this bottleneck could be crucial for future efforts to extend reproductive lifespan or delay menopause.
“We have thousands and thousands of oocytes in our bodies that we don’t need. If we figure out why they’re being lost without ever being ovulated, then we could tune the system. It could help keep the hormonal cycle going and help delay menopause, which half the world’s population must go through. The health and economic implications are enormous,” Böke explained.
Humans are born with about one million eggs, which dwindle to 400,000 by puberty and just 1,000 by menopause. Only about 400 are ever ovulated. Mice follow similar depletion patterns but on a smaller scale. Despite differences in timing- mice ovulate every few days, humans every month- the discovery that ovaries keep a fixed fraction of eggs primed may be a universal mammalian trait.
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The team has already shown their method works on human ovarian tissue, though a full lifespan study in humans would be far more challenging.
The team used cutting-edge tools like tissue clearing and whole-organ imaging at EMBL Barcelona’s Mesoscopic Imaging Facility, AI-driven image segmentation developed with collaborators at the Donostia International Physics Center, University of the Basque Country, and the Biofisika Institute, and an open-source platform, BiaPy, which makes the workflow, images, and trained AI model freely available to other labs.
“We wanted this tool to be useful to other scientists, not just for our own study. The complete workflow is freely available through BiaPy… That means other labs can check our work, or point the same method at their own images without having to build it from scratch,” said Ignacio Arganda-Carreras, co-developer of BiaPy.
This study reframes the ovary as an active, self-monitoring system rather than a passive egg bank. It also highlights how much variability exists even among genetically identical individuals, pointing to unknown developmental influences.
As Böke put it: “In my mind, this data should have been out there 20 years ago, so we could have started building on it. It really changes how experiments should be planned.”
Journal Reference:
- D’Angelo, A., Franco-Barranco, D., Musy, M. et al. Three-dimensional mapping of intact ovaries reveals the aging dynamics of the ovarian reserve. Nat Aging (2026). DOI: 10.1038/s43587-026-01178-z
