Physiology and Pathophysiology of the Primate Gonad

描述（申请人提供）：匹兹堡大学医学院生殖研究专业合作中心项目（SCCPRR）的使命仍然是研究生殖生理学，（整合基因组学）的控制系统，管理性腺功能的高等灵长类动物，包括人类。这使命匹兹堡SCCPRR，这反映了该中心长期以来的优势，即采用非人类灵长类动物模型来更好地了解人类生殖，并通过整合分子，细胞和系统方法进行研究。该中心将由两个技术服务核心（灵长类动物和分析）组成，采用开放获取格式，为六个SCCPRR项目（四个在匹兹堡），三个在莫尔豪斯医学院合作生殖科学中心的项目，以及其他几个由R01或R21赠款支持的项目提供服务。四个匹兹堡SCCPRR项目中的三个侧重于睾丸的发育和控制，特别强调精原干细胞（雄性生殖系干细胞，GSC）的增殖和分化的调节及其提供塞尔托利体细胞的生态位。减数分裂前精原细胞的研究将仅限于人类和猴子的睾丸，虽然支持细胞增殖和分化的分子生物学基础将与非灵长类动物模型阐明，我们的目标是同时翻译的结果在啮齿动物的猴子。第四个项目将使用非人类灵长类动物模型研究控制卵泡发育早期阶段的控制机制。概念和方法上的桥梁将这四个项目联系起来。在这方面，有平行的旁分泌控制卵泡发育，一方面，和男性生殖上皮的调节，另一方面。在技术层面上，匹兹堡中心开发的控制颗粒细胞基因表达的方法将直接应用于支持细胞生物学的研究。灵长类动物性腺的主题是探讨垂直平衡的调查经验，预计这种方法将保证匹兹堡SCCPRR将继续为我们的人类生殖的理解和治疗其疾病作出重大贡献。

DESCRIPTION (provided by applicant): The mission of the Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) at the University of Pittsburgh School of Medicine continues to be the study of the physiology (integrative genomics) of the control systems that govern gonadal function in higher primates, including man. This mission of the Pittsburgh SCCPRR, which reflects the long-standing forte of this Center to employ non-human primate models to better understand human reproduction, is pursued by integrating molecular, cellular and system approaches. The Center will be comprised of two Technical Service Cores (Primate and Assay) with an open access format to sub serve six SCCPRR projects (four in Pittsburgh), three projects at the Cooperative Reproductive Sciences Center at Morehouse School of Medicine, and several other programs supported by either R01 or R21 grants. Three of the four Pittsburgh SCCPRR projects focus on the development and control of the testes, with a particular emphasis on the regulation of proliferation and differentiation of stem spermatogonia (male germ-line stem cells, GSCs) and their niche providing somatic cells of Sertoli. Studies of premeiotic spermatogonia will be restricted to the human and monkey testes, and although the molecular biology underlying Sertoli cell proliferation and differentiation will be elucidated with non-primate models, we aim to concomitantly translate findings in the rodent to the monkey. The fourth project will examine the control mechanisms that govern the early stages of follicular development using a non-human primate model. Both conceptual and methodological bridges link the four projects. In this regard, there are parallels in the paracrine control of follicular development, on the one hand, and the regulation of the male germinal epithelium, on the other. At the technical level, methodology developed at the Pittsburgh Center for controlling gene expression in granulosa cells will find direct application to the study of Sertoli cell biology in this proposal. The theme of the primate gonad is explored with vertical balance in investigator experience, and it is anticipated that this approach will guarantee that the Pittsburgh SCCPRR will continue to contribute significantly to our understanding of human reproduction and to the treatment of its disorders.