Oocyte-expressed TGF-beta superfamily members in female fertility

Folliculogenesis is regulated by the interplay of extraovarian and intraovarian factors, and the importance of each type of regulation varies depending on the developmental stage of the follicle. Preantral follicle development is regulated predominantly by factors produced locally within the ovary and within the follicle itself. The oocyte has been shown to produce soluble factor(s), which regulate a number of processes in follicular development, including cumulus expansion in the periovulatory period. Members of the TGFbeta superfamily are potent regulators of cell proliferation and differentiation in a number of organ systems, and three members, growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15) and BMP-6 are expressed by the oocyte and may mediate effects attributed to the oocyte. Based on knockout mouse models BMP-6 does not play an essential role in ovarian function, but GDF-9 is absolutely required for preantral follicle development. GDF-9 also alters the periovulatory expression of granulosa cell genes and stimulates cumulus expansion. Although BMP-15 is expressed identically to GDF-9, its role in regulating ovarian function is still unknown. This review examines the similarities and differences in sequence, expression, and function of the oocyte-expressed TGFbeta family members with respect to regulating folliculogenesis.