Three-dimensional mapping of intact ovaries reveals the aging dynamics of the ovarian reserve
The spatiotemporal dynamics of the depletion of the ovarian reserve remain incompletely understood. Combining whole-ovary imaging, AI and modeling, the authors mapped over 85,000 mouse oocytes and found that ovaries main
Female fertility depends on a finite pool of oocytes that depletes during aging. Traditional methods obscure the three-dimensional architecture of the ovary, limiting quantitative insights. To address this, researchers employed light-sheet microscopy and artificial intelligence-driven segmentation to map over 85,000 mouse oocytes in whole ovaries across the reproductive lifespan. This approach enabled the authors to quantify the dynamics of ovarian reserve depletion and uncover underlying mechanisms. The study reveals that newly activated oocytes represent a fixed fraction of the total oocyte pool despite an age-related decline in oocyte numbers. Spatial analysis showed that oocytes are enriched along the lateral ovarian axis, and local oocyte density positively correlates with activation. Furthermore, a bimodal distribution of oocyte sizes was observed, suggesting a bottleneck during oogenesis. The findings also led to the development of a differential equation-based model capturing the kinetics of oocyte activation and loss. This quantitative framework provides new insights into ovarian aging and suggests that an organ-scale regulatory mechanism coordinates the age-related decline in oocyte numbers.