NanoCT-confocal mapping of mouse ovaries reveals lifespan-persistent symmetric organizational rules of primary-to-preovulatory follicles

Abstract

Mammalian ovaries are organized into follicles integrated with the surrounding tissue, collectively shaping an architecture continuously remodeled through cycles of growth and elimination. Combining nano-Computed Tomography with 3D digital modeling, we deciphered spatial rules governing follicle organization in the mouse ovary across lifespan. We find that primary to preovulatory follicles adopt a quantitatively symmetric arrangement along the anterior-posterior and dorsal-ventral axes, established during prepuberty before secondary follicle vascularization and preserved through adulthood and aging, regardless of follicle health or atresia. A novel nanoCT-confocal pipeline revealed that follicles enclosing oocytes with transcriptionally-active or transcriptionally-inactive chromatin states follow divergent fates of growth, atresia, or developmental competence, yet retaining a symmetric distribution. Mathematical modeling of follicle growth and elimination from prepuberty to adulthood identified transition rates between follicle stages that support gonadal symmetry. These findings suggest an evolutionarily optimized developmental program ensuring follicle recruitment and high ovulatory output, a hallmark of polytocous species.