Physiology and Pathophysiology of the Primate Gonad

描述(由申请人提供)：匹兹堡大学医学院生殖研究专业合作中心计划(SCCPRR)的任务仍然是研究控制包括人类在内的高等灵长类动物性腺功能的生理学(整合基因组学)。匹兹堡SCCPRR的这一使命反映了该中心长期以来的长处，即利用非人类灵长类模型更好地理解人类生殖，通过整合分子、细胞和系统方法来实现这一使命。该中心将由两个开放访问格式的技术服务核心(Primate和Assay)组成，为六个SCCPRR项目(匹兹堡四个)、莫尔豪斯医学院合作生殖科学中心的三个项目以及由R01或R21拨款支持的其他几个项目提供服务。匹兹堡SCCPRR的四个项目中有三个侧重于睾丸的发育和控制，特别强调对干细胞精原细胞(雄性生殖系干细胞)及其为Sertoli提供体细胞的利基环境的增殖和分化的调控。对减数分裂前精原细胞的研究将局限于人和猴子的睾丸，尽管支持细胞增殖和分化的分子生物学将通过非灵长类动物模型来阐明，但我们的目标是同时将啮齿动物的发现转化为猴子。第四个项目将使用非人类灵长类动物模型来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。在这一点上，一方面是对卵泡发育的旁分泌控制，另一方面是对男性生发上皮的调节。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本提案中的支持细胞生物学研究。灵长类性腺的主题是在研究人员的经验中垂直平衡地探索的，预计这种方法将保证匹兹堡SCCPRR将继续对我们对人类生殖及其疾病的治疗做出重大贡献。

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.