The role of pro-apoptotic BH3-only protein BMF in regulating the female fertile lifespan — ASN Events
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  3. The role of pro-apoptotic BH3-only protein BMF in regulating the female fertile lifespan

The role of pro-apoptotic BH3-only protein BMF in regulating the female fertile lifespan (#238)

Seng H Liew 1 , Kavitha Vaithiyanathan 1 2 , Michele Cook 3 , Andreas Villunger 4 , Philippe Bouillet 3 , Clare Scott 3 , Andreas Strasser 3 , Jock K Findlay 1 , Karla J Hutt 1 5
  1. Prince Henry's Institute of Medical Research, Clayton, Vic, Australia
  2. Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
  3. Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  4. Division of Developmental Immunology, University of Innsbruck, Innsbruck, Austria
  5. Department of Anatomy & Developmental Biology, Monash University, Clayton, Victoria, Australia

The length of the fertile lifespan and the age when menopause begins are influenced by the number of oocytes stored in the ovary as primordial follicles. Apoptosis, both during ovarian development and in the postnatal ovary, plays a critical role in determining the number of primordial follicles established and maintained within the ovary. However, the role of individual apoptotic proteins in mediating oocyte death has not yet been fully characterised. Our previous studies (Kerr et al. Mol Cell 2012; 48(3):343-52) showed that pro-apoptotic proteins belonging to the BH3-only subgroup of the Bcl-2 family are important initiators of oocyte/follicle death. In this study we investigated the role of BMF in determining primordial follicle number and fertile lifespan. Stereological analysis of ovaries showed that Bmf-/- mice had significantly more primordial follicles than WT control animals at postnatal days 100, 200 and 300 (WT 1318.2 ± 146.6 vs Bmf-/- 2456.2 ± 120.3 follicles/ovary, P<0.001; WT 791 ± 79.9 vs Bmf-/- 1461.8 ± 122.6 follicles/ovary, P<0.005; WT 358.5 ± 18.9 vs Bmf-/- 973.3 ± 33.1 follicles/ovary, P<0.0001, n=6/age/genotype). Following superovulation, no differences were observed in the numbers of ova shed between WT and Bmf-/- mice. Bmf-/- females were fertile and produced the same number pups/litter as WT when mated with WT males (8 ± 0.7 vs 7.5 ± 0.5 pups/litter, respectively, n=6/genotype), but Bmf-/- females produced more litters than WT over a 6 month period (WT 3.5 ± 0.5 vs Bmf-/- 5.5 ± 0.4 litters/breeder, n=6/genotype). Our findings suggest an important role for BMF in determining the number of primordial follicles maintained in the ovary throughout reproductive life. Long-term breeding studies are currently in progress to determine if the excess in primordial follicles conferred by loss of BMF will lead to a prolonged reproductive lifespan. This study will improve our understanding of how the length of the fertile lifespan is regulated.

This work was supported by the NHMRC of Australia (Program Grants #494802 and #257502, Fellowships JKF (#441101), KJH (#494836), CLS (#406675), AS (#461299); Victorian Government's Operational Infrastructure Support Program.

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