Physiology and Pathophysiology of the Primate Gonad

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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.