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 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 . Further studies have shown that the functional mature form of BMP-15 is barely detectable in mouse oocytes 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 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).