Biology of the Primate Ovarian Surface Epithelium

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The ovarian surface epithelium (OSE) is a monolayerthat normally undergoes repair and regrowth after each ovulation during natural menstrual cycles. Although it comprises less than 1/1,000th of the entire ovarian mass, it gives rise to nearly 90% of human ovarian cancers. Little is known about the characteristics and regulation of the OSE during the ovarian cycle, or its biological role(s). The long-term objective of this project is to understand the role of the OSE in ovarian biology and how its activities and regulation contribute to normal and pathologic situations in primates. Based on studies of OSE cells collected from rhesus monkeys, which share many characteristics with human OSE cells, experiments are proposed to test the hypotheses that the primate OSE: (a) is comprised of a dynamic population of cells that undergo proliferation, differentiation, and apoptosis as a function of proximity to dominant ovarian structures (i.e.the follicle destined to ovulate and the corpus luteum) and/or as a result of their exposure to the endocrine products of these structures (i.e.estrogen and progesterone), and (b) is essential for normal ovarian activities, notably timely ovulation of the dominant follicle. Experiments in rhesus macaques are designed to: Specific Aim #1: determine the surface distribution and characteristics, including proliferative and apoptotic indices, of the OSE throughout the menstrual cycle; Specific Aim #2: examine the effects of the dominant ovarian structures (the preovulatory follicle and corpus luteum), and steroid hormones (estradiol and progesterone) on OSE proliferation and death,and; Specific Aim #3: delineate the necessity of the OSE for ovarian function, including ovulation, repair, and prevention of intraperitoneal adhesions. This project will employ for the first time molecular and cellular techniques to examine gene expression, proliferation, and apoptosis in the primate OSE, and will rigorously evaluate its role in ovarian function during the menstrual cycle. Detailed information will accrue that provides a basis for further considerations of mechanisms leading to ovarian dysfunction (e.g. infertility) and pathology (e.g. tumorigenesis). The result of this project will generate a comprehensive tissue archive to be used in future studies and collaborations with other investigators.