The proapoptotic protein BID is dispensable for establishment of the ovarian reserve and overall fertility in mice

The size of the ovarian reserve established during early life is a key determinant of female reproductive lifespan, and is shaped by tightly regulated processes of follicle activation and apoptosis. However, the molecular pathways governing these events remain incompletely defined. BID is a pro-apoptotic BH3-only protein that links extrinsic death receptor signalling to the intrinsic mitochondrial apoptotic pathway, and has been implicated in cell death regulation in multiple tissues. Here, we investigated the role of BID in follicle dynamics and female fertility using Bid −/− mice. Ovaries from wild-type and Bid −/− mice were examined at postnatal day 1 (PN1) PN5, PN10 and PN50. Establishment of the ovarian reserve was not altered by loss of BID, as total germ cell numbers and ovarian morphology were comparable between genotypes. However, Bid −/− mice displayed a transient increase in primordial follicle activation at PN5, characterised by reduced primordial follicle numbers and increased primary follicles, with a corresponding rise in secondary follicles at PN10. This phenotype was not sustained at later stages. In adult ovaries, loss of BID resulted in a reduction in follicular atresia, with decreased numbers of atretic growing follicles and reduced granulosa cell apoptosis as assessed by TUNEL staining. Consistent with altered follicle dynamics, Bid −/− mice exhibited reduced numbers of corpora lutea in vivo. However, exogenous gonadotrophin stimulation revealed no difference in ovulatory capacity between genotypes. Despite these changes, Bid −/− females remained fully fertile, with only slight alterations in time to first litter and litter size, and no difference in cumulative pup output. Together, these findings demonstrate that BID is dispensable for establishment of the ovarian reserve and overall fertility, but contributes to the regulation of follicle activation and survival during postnatal ovarian development.