BIOLOGY OF THE PRIMATE OVARIAN SURFACE EPITHELIUM

灵长类动物卵巢表面上皮的生物学

• 批准号: 8173238
• 负责人: Jay W Wright
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173238
• 关键词: Animal Model; Biological Models; Biology; Cadherins; Cell Cycle Arrest; Cells; Chickens; Computer Retrieval of Information on Scientific Projects Database; Data; E-Cadherin; Epithelial ovarian cancer; Epithelium; Estrogens; Ethics; Etiology; Funding; Gene Expression; Grant; Health; Human; Institution; Macaca mulatta; Malignant neoplasm of ovary; Mammals; Menstrual cycle; Methods; Modeling; Ovarian; Ovary; Ovulation; Phase; Physiology; Primates; Progesterone; Proliferating; Protein Isoforms; Reporting; Research; Research Personnel; Resources; Risk; Source; Surface; System; United States National Institutes of Health; Woman; aged; base; human tissue; in vivo; nonhuman primate; novel therapeutics; reproductive; research study

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 is a suitable surrogate model for the human system on the basis of: (1). It has a shared reproductive and ovarian physiology and OSE; (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 OSEwith women that are not in common with nonprimate mammals. 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 regulate OSE cell dynamics in vivo by inducing cell cycle arrest in proliferating cells. 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).

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 上皮性卵巢癌的病因知之甚少，部分原因是它对灵长类动物(和鸡)的独特性限制了动物模型的可获得性。此外，正常灵长类卵巢表面上皮(OSE)的生物学还没有得到有效的研究，因此关于其转化原因的线索并不是基于经验观察。由于很难获得合适的人体组织(来自育龄妇女的健康卵巢)以及人类研究的实用和伦理限制，我们在以下基础上选择了非人类灵长类猕猴作为适合人类系统的代孕模型：(1)它具有共同的生殖和卵巢生理和OSE；(2)共同的基因表达，这在非灵长类哺乳动物中并不常见；以及(3)卵巢上皮细胞的报道 人类和非人类灵长类动物的癌症，而不是其他哺乳动物的癌症，强调了灵长类OSE与女性的潜在独特性，这与非灵长类哺乳动物不同。我们的目标是用免疫组织化学方法描述灵长类OSE在月经周期的不同阶段的特征；确定 卵巢因子(雌激素和孕激素)是否在体内动态调节OSE；以及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。我们还产生了实现赠款目标的初步数据，表明高水平的雌激素可能通过诱导增殖细胞的细胞周期停滞来调节体内OSE细胞的动力学。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)。