NOVEL CONTRACEPTIVES: CONTROL OF FOLLICULAR MATURATION AND RUPTURE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The events necessary for ovulation and, thus, fertilization include the development of an ovulatory follicle possessing a mature oocyte, follicle rupture, as well as the detachment of the oocyte and surrounding cumulus cells from the wall of the follicle. Follicle rupture and the release of an oocyte require significant cellular reorganization and remodeling of structural proteins that comprise the extracellular matrix (ECM) via a complex system of proteases. The release of the oocyte from the follicle also requires the separation of the cumulus-oocyte complex from the inner (granulosa) cell layer of the follicle wall. Cumulus-oocyte detachment involves loss of cell-cell contacts and formation of a hyaluronan-rich proteoglycan matrix between cumulus cells, resulting in a large increase or "expansion" of the cumulus-oocyte complex. Therefore, the molecular and cellular events allowing for follicle rupture and cumulus-oocyte complex expansion represent ideal targets for controlling the complex process of ovulation and hence fertility. Furthermore, controlling these aspects of ovulation are consistent with the novel concept that it is possible to selectively block fertility by preventing cumulus-oocyte expansion and/or follicle rupture without altering other aspects of female reproduction, including ovarian/menstrual cyclicity. Thus, due to their critical role as intermediates in the process of ovulation, this research serves to determine the contraceptive potential for manipulating the individual molecular components that allow for ovulation and cumulus-oocyte expansion.