Ovarian Follicle Selection Mediated by Release from Inhibitory Map Kinase Signaling

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In reproductively active vertebrate females that ovulate a limited number of eggs each ovulatory cycle, it is the rate-limiting process of ovarian follicle selection that ultimately determines the number of competent follicles eventually capable of being fertilized. Vertebrate follicle selection currently represents an incompletely defined process by which an undifferentiated follicle is activated to undergo final differentiation in preparation for ovulation, whereas the likely fate of those follicles not selected is follicle death. In the hen ovary, the ovulation of a single follicle per day requires an existing preovulatory hierarchy which normally consists of a limited number of fully differentiated follicles. This follicle hierarchy is maintained by the daily 'selection' of a single follicle from a small group of undifferentiated (prehierarchal) follicles measuring 6 to 8 mm in diameter. The novel hypothesis of the research proposed is that the selection of a single, prehierarchal follicle per day into the preovulatory hierarchy is first dependent upon the release of the follicle granulosa layer from inhibitory signaling, and subsequently dependent upon an increased sensitivity to Follicle-Stimulating Hormone. A central hypothesis tested herein is that the release from inhibitory Mitogen Activated Protein Kinase signaling is prerequisite for follicle selection in the avian ovary. Furthermore, it is proposed that such MAPK signaling is promoted by the local production of one or more members of the epidermal growth factor (EGF) family of peptides. The present project describes experiments using the hen ovary model system to study endocrine, novel paracrine and autocrine factors, together with their associated membrane receptors, that tightly regulate follicle selection and subsequent differentiation. Collectively, results from the study will determine critical cellular and molecular processes that define follicle selection (and by implication reproductive potential) in a vertebrate species. Interpretations of these data are predicted to pertain to all groups within the Sauropsid lineage (e.g., oviparous reptiles, crocodiles and birds) in which the establishment of an ovarian follicle hierarchy is prerequisite for egg laying. The PI has established a record of providing teaching and research training to graduate and undergraduate students of diverse backgrounds, and is committed to the professional development of female students. The PI is an ongoing participant in the Department's REU Summer Fellows Program that serves under-represented populations, and he routinely incorporates his related research expertise into his academic lecture and laboratory curricula.