GDF-9 and BMP-15: oocyte organizers.

Abstract

It has been long known that oocyte-secreted factors play key roles in development and differentiation of ovarian follicles, but the factors involved in folliculogenesis are not well characterized to date. The recent studies on two novel TGF β superfamily members, GDF-9 and BMP-15, have dramatically changed our view of ovarian physiology. GDF-9 has been shown to be obligatory for fertility in female mice by loss-of-function studies; in vitro studies further determined that GDF-9 is essential at multiple steps in the process of female reproduction. BMP-15, which shares high homology with GDF-9, seems not as essential as GDF-9 in fertility of female mice, though its expression pattern resembles GDF-9 quite closely. However, studies on sheep carrying natural mutations in the Bmp15 gene, FecXI and FecXH, show that BMP-15 is associated with infertility and super-fertility in a dosage-sensitive manner. Evidence from recent in vitro experiments also indicates that BMP-15 inhibits major FSH actions that are obligatory for follicle development and ovulation by suppressing FSH receptor expression in rats. Taken together, GDF-9 and/or BMP-15 may play dominant roles in female fertility in a species-dependent manner. Further studies to clarify the mechanisms by which GDF-9 and BMP-15 function will help us understand whether GDF-9, BMP-15, or both are essential for human fertility.