Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Peculiar features of GDF9 and BMP15 regulation of oocyte quality (#163)

Robert Gilchrist 1 2
  1. School of Womens & Childrens Health, Sydney, NSW
  2. School of Women’s & Children’s Health, University Of New South Wales, Sydney, NSW, Australia

Mammalian oocytes control their ovarian microenvironment through the production of potent oocyte-secreted factors (OSFs); principally growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15). During the late stages of folliculogenesis, oocyte secretion of GDF9 and BMP15 serves to specify the cumulus cell lineage of granulosa cells within the follicle, and in turn these cumulus cells support the growth and development of the oocyte as it prepares to sustain early embryogenesis. Native and recombinant OSFs have proven to be valuable additives to oocyte in vitro maturation (IVM), leading to notably increased embryo yields in vitro and pregnancy rates after transfer, as IVM may perturb GDF9 and/or BMP15 bioavailability. However, there are a number of peculiar features of the proteins. Unlike the rest of the TGFβ superfamily, GDF9 and BMP15 do not form covalent dimers and may exist as either non-covalent hetero- or homo-dimers. There are important interactions between the two growth factors including potent synergism. Furthermore, there are striking differences in the role and potency of the proteins between species, e.g. mouse GDF9 is potent whereas human GDF9 is latent. It is currently unclear what molecular forms of GDF9 and BMP15 are secreted by the oocyte. Curiously, mature domain homodimers of GDF9 and/or BMP15, which are biologically potent proteins, do not affect mouse or bovine oocyte developmental competence. By contrast, processed complexes of pro- and mature-homodomains improve bovine/porcine (pro-hBMP15) and mouse (pro-mGDF9) oocyte quality, with further improvements using GDF9+BMP15. Pro-hGDF9 is inactive, however, when selected residues from mouse GDF9 that are predicted to affect pro-mature domain interactions are incorporated into the human protein, pro-hGDF9 also enhances oocyte quality. GDF9 and BMP15 are powerful regulators of oocyte quality and are high value IVM additives, however there are complex cell-specific and species-specific mechanisms controlling their actions.