BIOLOGY OF THE PRIMATE OVARIAN SURFACE EPITHELIUM

Oregon Health & Science University, Portland OR

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Abstract

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 etiology of epithelial ovarian cancer is poorly understood, in part because its uniqueness to primates (and chickens) limits the availability of an animal model. In addition, the biology of the normal primate ovarian surface epithelium (OSE) has not been effectively studied, so clues to the causes of its transformation are not based on empirical observation. Due to the difficulty in obtaining appropriate human tissue (healthy ovaries from reproductively aged women) and the practical and ethical limitations on human studies, we selected the nonhuman primate rhesus monkey as a surrogate model for the human system on the basis of: (1) shared reproductive and ovarian physiology;(2) shared gene expression that is not common to nonprimate mammals;and (3) reports of epithelial ovarian cancer in human and nonhuman primates, but not other mammals, that emphasize the potential uniqueness of the primate OSE. Our aims are to characterize the primate OSE at distinct phases of the menstrual cycle using immunohistochemical methods;to determine whether ovarian factors (estrogen and progesterone) dynamically regulate the OSE in vivo;and to establish whether the OSE is an essential component of ovarian function and health. This project will establish a fundamental baseline to understand the primate OSE and provide a model system for hypothesis-based experiments to evaluate risks for ovarian cancer and novel therapeutic strategies.