BMP-15 regulation of ovulation quota in mammals.

Naturally occurring mutations in the oocyte-specific factor, bone morphogenetic protein-15 (BMP-15), cause infertility in women and in ewes. In contrast to these monoovulatory mammals, the targeted deletion of BMP-15 in polyovulatory mice results in subfertility with only minimal defects in the ovulation process. Given the established role of BMP-15 in governing the progression of folliculogenesis, it is hypothesized that species-specific differences in the BMP-15 system are involved in species-specific determination of ovulation quota and litter size. Recent data using in vitro cell transfection methodology indicate that, in contrast to human BMP-15 which is successfully processed and secreted, the mouse BMP-15 proprotein is resistant to proteolytic cleavage. Thus, no functional mature BMP-15 is secreted in vitro. Further studies have shown that the functional mature form of BMP-15 is barely detectable in mouse oocytes in vivo until just before ovulation, when it is markedly increased. The general hypothesis to emerge from these observations is that the species-specific differences in the defects caused by mutations in the bmp15 gene between monoovulatory ewes and women and polyovulatory mice might be attributed to the timing of the production of BMP-15 mature protein. (Reprod Med Biol 2006; 5: 245-248).