Poster Presentation ESA-SRB Conference 2015

BMF regulates primordial follicle loss during adolescence (#301)

Seng H Liew 1 , Nadeen Zerafa 1 , Jeffrey Kerr 1 , Michele Cook 2 , Philippe Bouillet 2 , Clare L Scott 2 , Andreas Strasser 2 , Jock K Findlay 3 , Karla J Hutt 1
  1. Department of Anatomy & Developmental Biology, Monash University, Clayton, Victoria, Australia
  2. Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  3. Hudson Institute of Medical Research, Clayton, Victoria, Australia

In mammalian ovaries, the primordial follicle pool, known as the ovarian reserve, determines female fertility and reproductive lifespan. Cell death during ovarian development in the embryo plays a critical role in determining how many primordial follicles are established within the ovary. While much attention has focussed on the apoptotic elimination of germ cells prior to and during primordial follicle assembly, the precise mechanisms that govern the steady postnatal depletion of primordial follicles after their initial endowment remain uncharacterised. In particular, there are few studies that address follicular dynamics and primordial follicle loss during adolescence. In this study we investigated the role of Bcl-2 modifying factor (BMF), a pro-apoptotic BH3-only protein belonging to the BCL-2 superfamily, in regulating primordial follicle loss in prepubertal, adolescent and adult mice (postnatal (PN) 20-100). Primordial follicle numbers were comparable in ovaries from WT and Bmf-/- at PN20, 30 and 40 (WT 4641.0 ± 404.7 vs Bmf-/- 4146.8 ± 420.5 follicles/ovary, P=0.42; WT 3899.1 ± 249.3 vs Bmf-/- 3943.6 ± 339.2 follicles/ovary, P=0.92; WT 3804.5 ± 286.9 vs Bmf-/- 5254.0 ± 1082.7 follicles/ovary, P=0.15). However, a 50% reduction in the number of primordial follicles was observed in ovaries from WT mice between PN40 and PN50 (WT PN40 3804.5 ± 286.9 vs WT PN50 2058.8 ± 277.1 follicles/ovary, P<0.002), while a reduction in 25% of primordial follicles was observed in ovaries from Bmf-/- mice during this same time period (Bmf-/- PN40 5254.0 ± 1082.7 vs Bmf-/- PN50 3316.3 ± 428.4 follicles/ovary, P<0.05). Collectively, these data indicate that primordial follicles are lost in significant numbers during the transition to adulthood and that BMF is required for this process. The reason for the elimination for such large numbers of primordial follicles immediately prior to the establishment of adult ovarian reserve is unknown and will be the focus of future investigations.