Establishing the baseline: understanding follicle activation morphometrics in multiple mammalian species†

Folliculogenesis encompasses many stages as the somatic granulosa and theca cells support oocytes through growth and maturation. A novel follicle stage, between primordial and transitional stages, was identified in mice and defined as "zip." Like all other follicle stages, the "zip" stage is characterized by its granulosa cell morphology. The "wedge" GC morphology in zip follicles is predicted to be the first granulosa cell division, marking the transition from squamous to cuboidal morphology. Here, zip and transitional stages were identified in histological sections of porcine, bovine, rhesus monkey, and human ovaries. Several growth dynamics characterized at these follicle stages were conserved between species. Oocyte diameter and area increased between the primordial and transitional stages in the porcine ovary and between the primordial and primary stages in the rhesus monkey ovary but appeared unchanged in bovine and human ovaries. In all species except for pigs, granulosa cell number and height increased at stages earlier than observed changes in the oocyte. Furthermore, there were differences in the percentage of zip and transitional follicle stages present in the cortical region across species. This implies that there may be species-dependent activation and growth mechanisms that require further study. The parameters defined here for identifying and characterizing the zip and transitional follicle stages across species can act as a tool for measuring factors that perturb or induce primordial follicle activation or effect follicle morphometric parameters in support of future innovations for fertility preservation and restoration.