Oral Presentation ESA-SRB-APEG-NZSE 2022

Dominant follicle selection in mice (#258)

Sharon Richard 1 , Yiran Zhou 1 , Michael W Pankhurst 1
  1. Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

Mono-ovulatory dominant follicle selection is well-characterised through ultrasound studies tracking daily changes in follicle size during the ovarian cycle follicular phase. Poly-ovulatory dominant follicle selection is less clear due to difficulty tracking each antral from day-to-day with certainty. This study aimed to examine dominant follicle development in mouse ovaries to determine if the preovulatory follicles are recruited as a single, large cohort or if preovulatory follicles are recruited progressively across the estrous cycle. Mice were injected with of bromodeoxyuridine (BrdU) at estrus, metestrus and were euthanised 2 hours later. Incorporation of BrdU into the DNA of proliferating granulosa cells was detected by immunohistochemistry and mitotic indexes for 622 growing follicles were quantified using machine-learning image-analysis. Preantral follicles exhibited the lowest mitotic index but follicles underwent a growth spurt in the early antral stage, reaching their maximal rate of proliferation. Declining mitotic indexes were seen as follicles developed to the preovulatory stage. Few atretic follicles were observed at estrus but large numbers were present at estrus and diestrus. Interestingly, the atresia occurred in follicles beyond 170 µm indicating that this represents the onset of gonadotropin-dependent phase, which is substantially larger in vitro estimates. Preovulatory-sized follicles were rare at estrus but increasingly present at metestrus. Full preovulatory cohorts were established by diestrus, indicating that this phase is similar to follicle deviation (selection) in mono-ovulatory species. These data indicate that preovulatory cohorts accumulate progressively during the estrus cycle. Mathematical models of follicle growth established that there are two possible classes of follicles that can become preovulatory; (1) medium antral follicles that survived under low-FSH conditions at the end of the previous cycle and (2) small antral follicles with high mitotic indexes that can theoretically overtake slow-growing medium antral follicles. Future studies will examine how follicles can acquire the characteristics of future preovulatory follicles.