CENTER FOR REPRODUCTIVE SCIENCES

堪萨斯大学医学中心提议建立一个U54生殖研究专业合作中心，解决与男性、女性不孕症相关的前沿分子和细胞问题，并建立早孕。三个核心和四个研究项目是由杰出和知名的生殖生物学家提出的，他们致力于这一领域。项目一，性腺中SF-1表达的调控，将利用啮齿动物模型系统确定睾丸中调节SF-1表达的交易因子，表征调节SF-1表达的转录因子USF1和2，并确定SF-1正确时空表达所需的Ftz-Z1基因的最小区域。SF-1在性腺发育和甾体形成中的关键性质强调了识别导致SF-1诱导和响应SF-1活性的事件的重要性。项目II， Src酪氨酸激酶调节卵巢功能，将研究小鼠和人类及其在卵巢卵泡发育机制中的作用，通过Src酪氨酸激酶调节卵巢细胞对促性腺激素的反应。项目三，着床期间子宫血管变化和血管生成方面，将在小鼠身上验证血管内皮细胞生长因子及其受体和神经匹林-1是着床和脱囊化所需的血管通透性和血管生成的重要介质的假设。此外，有假设认为，环氧化酶-2缺失小鼠着床失败是由于这些基因在着床围关键时期子宫异常表达的结果。项目四，TRAIL和人类植入部位，将研究滋养细胞TRAIL及其受体在植入部位调节免疫相互作用以及指导早期人类胎盘发育和功能中的作用。细胞培养和组织分析核心以及成像核心是建立良好的，具有成本效益的核心，将作为开放获取的核心运行，因为有许多NICHD批准了核心访问，以补充U54项目。行政核心将促进科学交流，协助管理U54核心和项目。总体而言，堪萨斯U54中心是该机构三十多年来的主要关注点，它将成为促进当代生育和不孕症研究的高效、经济的工具。

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.