Molecular biology and physiological role of the oocyte factor, BMP-15.

The oocyte factor, bone morphogenetic protein-15 (BMP-15) has proven to be critical for normal fertility in female mammals. The biological functions of recombinant BMP-15 demonstrate its capacity to promote granulosa cell processes involved in early follicle growth, while simultaneously acting to restrict follicle-stimulating hormone (FSH)-induced granulosa cell differentiation. The in vitro biological activities of BMP-15 demonstrate its role in promoting early follicle growth through the stimulation of granulosa cell mitosis while simultaneously restricting FSH-induced follicle development through the suppression of FSH receptor mRNA expression. The in vivo relevance of the role of BMP-15 was established by the identification of naturally occurring BMP-15 mutations in sheep, which cause infertility in homozygous carrier ewes and, in striking contrast, increased fecundity in heterozygous carrier ewes due to an increase in ovulation quota. The necessity of BMP-15 for folliculogenesis in women has been recently established by the discovery of a BMP-15 mutation that is associated with ovarian dysgenesis. In contrast to the pronounced effects that the BMP-15 mutations have on folliculogenesis in sheep and humans, mice, which are homozygous for targeted deletions of BMP-15 exhibit only minimal defects in the ovulation process, leading to the proposal that there may be causal differences in the BMP-15 system of mono- and polyovulatory animals. Collectively, recent research on the oocyte-secreted factor BMP-15 has provided exciting new opportunities for understanding ovarian physiology and female fertility.