Three-dimensional mapping of intact ovaries reveals the aging dynamics of the ovarian reserve.
basic_science · Level V
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- Record sourced from PubMed, PMID 42587142.
- Also identified by DOI 10.1038/s43587-026-01178-z.
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Abstract
Female fertility depends on a finite pool of oocytes that depletes during aging<sup>1,2</sup>, yet the spatiotemporal dynamics of this depletion remain poorly understood. Traditional methods obscure the three-dimensional architecture of the ovary, limiting quantitative insights. Here we combine light-sheet microscopy, artificial intelligence-driven segmentation and mathematical modeling to map over 85,000 oocytes in whole ovaries across the reproductive lifespan in mouse. We find that newly activated oocytes represent a fixed fraction of the total oocyte pool despite an age-related decline in oocyte numbers. Spatial analysis revealed that oocytes are enriched along the lateral ovarian axis, and local oocyte density positively correlates with activation. We also uncover a bimodal distribution of oocyte sizes, suggesting a bottleneck during oogenesis. Finally, a differential equation-based model captures the kinetics of oocyte activation and loss. Our findings establish a quantitative framework for understanding ovarian aging and suggest that an organ-scale regulatory mechanism coordinates the age-related decline in oocyte numbers.