CENTER FOR REPRODUCTIVE SCIENCES

堪萨斯大学医学中心建议建立一个U54生殖研究专业合作中心，解决与男性、女性和早孕相关的不孕不育的尖端分子和细胞问题。三个核心和四个研究项目是由杰出的和知名的生殖生物学家提出的，他们把自己的职业生涯献给了这个领域。项目I，性腺中SF-1表达的调节，将使用啮齿动物模型系统来识别调节睾丸中SF-1表达的调控因子，表征调控SF-1表达的转录因子USF1和2，并确定正确表达SF-1所需的FTZ-Z1基因的最小区域。SF-1在性腺发育和类固醇合成中的关键性质强调了识别导致SF-1诱导和响应SF-1 S活性的事件的重要性。项目II，Src酪氨酸激酶调节卵巢功能，将在小鼠和人类身上研究其在卵巢卵泡发育机制中的作用，通过该机制，Src酪氨酸激酶调节卵巢细胞对促性腺激素的反应。项目III，植入过程中子宫血管变化和血管生成的方面将在小鼠身上验证这样的假设，即血管内皮细胞生长因子、其受体和神经粘连蛋白-1是植入和蜕膜所需的血管通透性和血管生成的重要介质。另外，环氧合酶-2基因缺失小鼠的着床失败可能是这些基因在关键的着床期子宫中异常表达的结果。项目四，TRAIL和人类着床部位，将研究滋养细胞TRAIL及其受体在调节着床部位的免疫相互作用以及指导早期人类胎盘的发育和功能中的作用。细胞培养和组织分析核心和成像核心是成熟的、具有成本效益的核心，将作为开放获取运作，因为有许多NICHD赠款被批准用于核心获取，以补充U54项目。行政核心将促进科学交流，并协助管理U54核心和项目。总体而言，堪萨斯U54中心三十多年来一直是该机构的主要关注点，它将成为促进当代生育和不孕不育研究的有效、成本效益高的工具。

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.