Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: Loss of the Pro-Apoptotic BH3-Only Protein BCL-2 Modifying Factor (BMF) Prolongs the Fertile Lifespan in Female Mice. Liew SH 2014 et al. The duration of the female fertile lifespan is influenced by the number of oocytes stored in the ovary as primordial follicles. Cell death, both during ovarian development in the embryo and in the postnatal ovary, plays a critical role in determining how many primordial follicles are established and maintained within the ovary. However, the roles of individual apoptotic regulators in mediating cell death within the ovary have not yet been characterized. In this study, gene targeted mice were used to investigate the role of BCL-2-modifying factor (BMF), a pro-apoptotic protein belonging to the BH3-only subgroup of the BCL-2 family, in determining the number of primordial follicles maintained in the adult ovary and the length of the fertile lifespan. Stereological analysis of ovaries showed that Bmf(-/-) mice had significantly more primordial follicles than wild-type (WT) control animals at Postnatal Days 100, 200, 300 and 400, but not at Day 20. No differences were observed between WT and Bmf(-/-) mice in the number of ova shed following ovulatory stimulation with exogenous gonadotropins. Bmf(-/-) females were fertile and produced the same number pups/litter as WT females, but Bmf(-/-) females produced litters more frequently, and consequently more offspring, than WT females over a 6 mo period. Furthermore, the fertile lifespan of Bmf(-/-) females was significantly extended compared to WT females. Our findings support an important role for BMF in determining the number of primordial follicles maintained in the ovary throughout adult reproductive life and thus indicate that the length of female fertility may be extended by increasing the number of primordial follicles maintained within the ovary through inhibition of BMF. /////////////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: fertile
Comment: BCL-2 modifying factor promotes germ cell loss during murine oogenesis. Vaithiyanathan K et al. (2016) Apoptosis plays a prominent role during ovarian development by eliminating large numbers of germ cells from the female germ line. However, the precise mechanisms and regulatory proteins involved in germ cell death are yet to be determined. In this study we characterised the role of the pro-apoptotic BH3-only protein, BCL-2 modifying factor (BMF), in germ cell apoptosis in embryonic and neonatal mouse ovaries. BMF protein was immunohistochemically localised to germ cells at embryonic days (E) 15.5, 17.5 and postnatal day (PN) 1, coincident with entry into the meiotic prophase, but was undetectable at E13.5, and only present at low levels at PN3 and PN5. Consistent with this expression pattern, loss of BMF in female mice was associated with a decrease in apoptosis at E15.5 and E17.5. Furthermore, increased numbers of germ cells were found in ovaries from Bmf-/- mice compared to wild-type (WT) animals at (E) 15.5 and PN1. However, germ cell numbers were comparable between Bmf-/- and WT ovaries at PN3, PN5 and PN10. Collectively, these data indicate that BMF mediates fetal oocyte loss and its action limits the maximal number of germ cells attained in the developing ovary, but does not influence the number of primordial follicles initially established in ovarian reserve.//////////////////