BIOLOGY OF THE PRIMATE OVARIAN SURFACE EPITHELIUM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 上皮性卵巢癌(EOC)的病因目前知之甚少。卵巢表面上皮(OSE)是女性卵巢上皮细胞的来源，但目前对其研究还不够深入，这限制了卵巢癌治疗策略的发展。由于人体研究的不可行性，我们选择恒河猴作为研究OSE的替代模型。猕猴在生殖和基因上与女性相似，EOC存在于其他非人类灵长类动物中，但不存在于非灵长类动物中。我们的目标是用免疫组织化学方法研究灵长类OSE在月经周期不同阶段的特征；确定卵巢因素(雌激素和孕酮)是否在体内动态调节OSE；以及确定OSE是否是卵巢功能和健康的重要组成部分。该项目将建立一个了解灵长类OSE的基本基线，并为基于假设的实验评估卵巢癌的风险和新的治疗策略提供一个模型系统。我们已经证明OSE不是排卵所必需的。我们还生成了实现赠款目标的初步数据，表明高水平的雌激素可能会刺激体内OSE的增殖。我们已经进行了免疫组织化学研究，确定E-钙粘蛋白是OSE体内表达的主要钙粘附素亚型，并证实这一点在女性OSE中也是如此(与其他人的发现相反)。由于灵长类OSE在排卵中没有明显的作用，它的消除可能为EoC的预防提供一种新的策略。

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.