The University of Kansas Medical Center proposes to establish a U54 Specialized Cooperative Center in Reproductive Research that addresses cutting edge molecular and cellular issues of infertility related to male, female, and establishment of early pregnancy. Three cores and four research projects are proposed by outstanding and well-known reproductive biologists who have dedicated their careers to this field. Project I, Regulation of SF-1 Expression in the Gonads, will use a rodent model system to identify transacting factors regulating SF-1 expression in the testis, characterize the transcription factors, USF1 and 2, regulating SF-1 expression, and identify the minimal region of the Ftz-Z1 gene required for correct spatial and temporal expression of SF-1. The pivotal nature of SF-1 in gonadal development and steroidogenesis underscores the importance of identifying events leading to SF-1 induction and those responsive to SF-1's activity. Project II, Src Tyrosine Kinase Regulates Ovarian Function, will examine in mice and humans and its role in ovarian follicular development mechanisms by which Src tyrosine kinase regulates responses of ovarian cells to gonadotropins. Project III, Aspects of Uterine Vascular Changes and Angiogenesis during Implantation will test in mice the hypothesis that vascular endothelial cell growth factor, its receptors and neuropilin-1 are important mediators of vascular permeability and angiogenesis required for implantation and decidualization. In addition, it is hypothesized that failure of implantation in cyclooxygenase-2 null mice is the result of aberrant uterine expression of these genes during the critical peri-implantation period. Project IV, TRAIL and the Human Implantation Site, will investigate the role of trophoblastic TRAIL and its receptors in modulating immunological interactions at the implantation site as well as directing development and function in early human placentas. The Cell Culture and the Tissue Analysis Core and Imaging Core are well established, cost effective cores that will operate as open access since there are numerous NICHD grants approved for core access that complement the U54 projects. The Administrative Core will promote scientific exchange and assist in management of U54 cores and projects. Overall, the Kansas U54 Center, which has been a major focus in this institution for more than three decades, will serve as an efficient, cost-effective vehicle for promoting contemporary research on fertility and infertility.
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