Biology of the Primate Ovarian Surface Epithelium

描述（由申请人提供）：卵巢表面上皮（OSE）是一种单层细胞，在自然月经周期中每次排卵后通常经历修复和再生。虽然它占整个卵巢肿块的不到千分之一，但它引起了近90%的人类卵巢癌。关于卵巢周期中OSE的特征和调控，或其生物学作用，我们知之甚少。该项目的长期目标是了解OSE在卵巢生物学中的作用，以及它的活动和调节如何影响灵长类动物的正常和病理情况。基于对从恒河猴身上采集的OSE细胞的研究，我们提出了实验来验证灵长类动物OSE细胞的假设：(a)由一群动态的细胞组成，这些细胞经历增殖、分化和凋亡，这是与卵巢优势结构（即注定要排卵的卵泡和黄体）接近的功能，或者是它们暴露于这些结构的内分泌产物（即雌激素和黄体酮）的结果，(b)对正常卵巢活动至关重要，尤其是优势卵泡的及时排卵。在恒河猴中进行的实验旨在：特定目的#1：确定整个月经周期中OSE的表面分布和特征，包括增殖和凋亡指数；具体目标#2：检查主要卵巢结构（排卵前卵泡和黄体）和类固醇激素（雌二醇和黄体酮）对OSE增殖和死亡的影响；具体目的#3：描述OSE对卵巢功能的必要性，包括排卵、修复和预防腹腔内粘连。本项目将首次采用分子和细胞技术检测灵长类动物OSE的基因表达、增殖和凋亡，并将严格评估其在月经周期中对卵巢功能的作用。详细的信息将为进一步考虑导致卵巢功能障碍（如不孕症）和病理（如肿瘤发生）的机制提供基础。这个项目的结果将产生一个全面的组织档案，用于未来的研究和与其他研究者的合作。

DESCRIPTION (provided by applicant): The ovarian surface epithelium (OSE) is a monolayer that 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.