This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The etiology of epithelial ovarian cancer (EOC)is poorly understood. The ovarian surface epithelium (OSE), the source of EOC in women, has not been effectively studied, which has limited progress in developing strategies for EOC treatment. Due to the infeasibility of human studies, we selected the rhesus monkey as an alternative model to study the OSE. The macaque is reproductively and genetically similar to women, and EOC occurs in other nonhuman primates, but not nonprimates.
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. We have demonstrated that the OSE is not required for ovulation. We also have generated preliminary data in fulfillment of grant aims, indicating that high levels of estrogen may stimulate proliferation in the OSE in vivo. We have performed immunhistochemical studies that identify E-cadherin as the predominant cadherin isoform expressed by OSE in vivo, and confirmed this is true in the OSE of women as well (in contrast to the findings of others). Because the primate OSE has no apparent role in ovulation, its elimination may provide a novel strategy for EOC prevention.
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