Folliculogenesis is a precise series of developments that require the cooperative efforts of several cell types comprising the Graafian follicle and the integration and modulation of a complex set of hormonal and non-hormonal messages (including those that act by way of autocrine and paracrine mechanisms) that ultimately insure maturation and survival of the oocyte and finally bring about its ovulation. Basic to any attempt to elucidate the integrated function of the developing Graafian follicle is the need to understand the unique structural and physiological features of each component. A defect in one cell type or one component may have marked repercussions on another constituent of the follicle. This may contribute to infertility, which affects about 10-15% of all couples in the United States. The objective of this proposal is to learn some of the basic, fundamental aspects of the dynamic morphology and function of the oocyte, the multifunctional granulosa cell and theca, as each is related to follicular development under normal and experimental conditions, i.e., the production of ovarian cysts (cystogenesis) by treatment with dehydroepiandrosterone (DHEA).
THE SPECIFIC AIMS OF THIS PROPOSAL ARE: (A) TO DETERMINE THE EFFECT(S) OF DEHYDROEPIANDROSTERONE (DHEA) TREATMENT ON ONGOING FOLLICULOGENESIS AND SERUM HORMONES BEFORE AND AT THE ONSET OF CYSTOGENESIS; (B) TO DETERMINE THE PARTICIPATION OF GROWTH FACTORS DURING FOLLICULOGENESIS IN NORMAL OVARIES AND FROM OVARIES OF ANIMALS TREATED WITH DHEA AT THE ONSET AND DURING CYSTOGENESIS; (C) TO DETERMINE THE EFFECTIVENESS OF ANDROGEN(S) (DHEA AND ITS METABOLITES), GONADOTROPINS, OR COMBINATIONS THEREOF ON GRANULOSA CELLS DURING FOLLICULOGENESIS AND CYSTOGENESIS; (D) TO DETERMINE THE EFFECT OF THE OOCYTE ON FOLLICULOGENESIS AND CYSTOGENESIS; AND (E) TO DETERMINE THE FUNCTION OF THE CYTOSKELETON DURING FOLLICULOGENESIS AND CYSTOGENESIS. THE PROPOSED EXPERIMENTS WILL USE IN VIVO AND IN VITRO TECHNIQUES, PHASE CONTRAST MICROSCOPY, LASER SCANNING CONFOCAL MICROSCOPY, ELECTRON MICROSCOPY, IMMUNOHISTOCHEMISTRY, REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION, IN SITU HYBRIDIZATION, AND PROTEIN BIOCHEMICAL TECHNIQUES. The expected fundamental data will be integrated with that obtained about the reproductive process in general through other biological disciplines.
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