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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 上皮性卵巢癌的病因学知之甚少，部分原因是其对灵长类（和鸡）的独特性限制了动物模型的可用性。 此外，正常灵长类动物卵巢表面上皮（OSE）的生物学尚未得到有效研究，因此其转化原因的线索并不基于经验观察。 由于难以获得适当的人体组织（来自育龄妇女的健康卵巢）以及人体研究的实践和伦理限制，我们选择非人灵长类恒河猴作为人体系统的合适替代模型，基于：（1）。 它具有共同的生殖和卵巢生理学和OSE;（2）非灵长类哺乳动物不常见的共同基因表达;（3）上皮卵巢癌的报道。 在人类和非人类灵长类动物，但不是其他哺乳动物的癌症，这强调了灵长类动物的潜在独特性，与妇女是不常见的非灵长类哺乳动物。 我们的目的是用免疫组织化学方法来描述灵长类动物OSE在月经周期不同阶段的特征，以确定 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。 该项目将建立一个基本的基线，以了解灵长类动物OSE，并提供一个基于假设的实验模型系统，以评估卵巢癌的风险和新的治疗策略。我们已经证明OSE不是排卵所必需的。 我们也产生了初步的数据，在实现赠款的目标，表明高水平的雌激素可能会调节OSE细胞的动态在体内诱导细胞周期停滞增殖细胞。 我们已经进行了免疫组化研究，确定E-cadherin作为OSE在体内表达的主要钙粘蛋白亚型，并证实这在女性OSE中也是如此（与其他人的发现相反）。