The Role of Bone Morphogenetic Proteins in Ovarian Function

Bone morphogenetic proteins (BMPs) represent the largest subclass of growth factors in the transforming growth factor beta (TGF-beta) superfamily. BMPs have proven to be multifunctional regulators of a wide variety of biological processes in numerous types of cell and tissue. The role of inhibins, activins and TGF-betas (which also belong to the TGF-beta superfamily) in reproduction has been studied extensively over the last 15 years. However, there were no reports on the role of BMPs in the mammalian ovary until 1999 when we reported an intrinsic ovarian BMP system replete with BMP ligands, receptors and novel biological functions. Since this report it has become clear that the BMP system plays an important role in the regulation of ovarian function, evidenced by the ability of BMPs to control granulosa cell proliferation and cytodifferentiation, as well as oocyte development. The physiological relevance of the BMP system has recently been highlighted by the discovery that genetic mutations in the BMP-15 ligand or the BMP type IB receptor lead to critical aberrations in folliculogenesis and ovulation. This review provides a current overview of the rapidly emerging field of the BMP system in mammalian ovarian function.