Loss of the Pro-Apoptotic BH3-Only Protein BCL-2 Modifying Factor (BMF) Prolongs the Fertile Lifespan in Female Mice

Liew, SH; Vaithiyanathan, K; Cook, M; Bouillet, P; Scott, CL; Kerr, JB; Strasser, A; Findlay, JK; Hutt, KJ

Author(s): Liew, SH; Vaithiyanathan, K; Cook, M; Bouillet, P; Scott, CL; Kerr, JB; Strasser, A; Findlay, JK; Hutt, KJ;
Details: Publication Year 2014-04-10,Volume 90,Issue #4,Page 77
Journal Title: Biology of Reproduction
Publication Type: Journal Article
Abstract: 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.
Publisher: The Society for the Study of Reproduction
Keywords: Apoptosis, Atresia, Fertility, Follicle, Ovary
Research Division(s): Molecular Genetics Of Cancer; Stem Cells And Cancer
Publisher's Version: https://doi.org/10.1095/biolreprod.113.116947

Creation Date: 2014-03-19 09:37:26