Molecular Basis of Male Infertility

描述（由申请人提供）：本申请寻求对贝勒医学院NICHD资助的P01计划项目的继续支持，以使用最先进的遗传学研究男性不育症。该方案项目的核心是一个核心行政单位，负责协调基础和临床科学家的日常活动。该计划项目的研究重点领域是人类非梗阻性无精子症的DNA修复缺陷和卵胞浆内单精子注射（ICSI）对儿童的影响，睾丸精原细胞增殖的分子控制，导致活力和精子-卵子相互作用缺陷的基因缺陷。这些项目将受益于组织采购/分子技术核心，用于分析来自生育和不育男性的大量人类样本，以快速临床转化基础研究结果。该提案的总体目标仍然是：继续为男性不育症的研究提供一个项目奖，该项目奖在泌尿科、妇产科、分子和细胞生物学、病理学和分子人类遗传学等部门的基础和临床科学家之间建立了密切的工作关系。在一个计划项目中促进这些群体之间的密切工作关系比这些科学家单独工作更有效地关注男性不育症。创建组织采购/分子技术设施，为研究者提供来自生育和不育男性的充分表征的组织，以将基础研究结果快速转化为临床竞技场。自发的，转基因的，和敲除小鼠模型的男性生殖缺陷的计划项目的研究人员提供了一个重要的和关键的资源，为最终的临床翻译。将男性不育的临床特征与分子水平的新发现相关联，以更好地了解疾病过程，从而开发新的和更有效的治疗和诊断方式。这个多学科科学家小组的专业知识，共同努力，预计将产生新的理解的基本病理生理学的男性不育症。

DESCRIPTION (provided by applicant): This application seeks support for the continuation of an NICHD funded P01 Program Project at Baylor College of Medicine to study male infertility using state-of-the-art genetics. The Program Project has as its nucleus a core administrative unit that coordinates the activities of the basic and clinical scientists on a day-to-day basis. The areas of research focus of this Program Project are DNA repair defects in human non obstructive azoospermia and the consequences for children conceived by intracytoplasmic sperm injection (ICSI), the molecular control of spermatogonial cell proliferation in the testes, gene defects resulting in motility and sperm-egg interaction defects. These projects will benefit from the Tissue Procurement/Molecular Techniques Core for the analysis of large numbers of human samples from fertile and infertile men for the rapid clinical translation of the basic research findings. The overall aims for the proposal remain: To continue a Program Project Award for the study of male infertility that creates a close working relationship between basic and clinical scientists from the Departments of Urology, Obstetrics and Gynecology, Molecular and Cellular Biology, Pathology and Molecular Human Genetics. Facilitation of the close working relationships among these groups in one Program Project more effectively focuses on male infertility than would occur with these scientists working individually. To create a Tissue Procurement/Molecular Techniques facility that will provide well-characterized tissue from fertile and infertile men to investigators to rapidly translate the basic research findings to the clinical arena. The spontaneous, transgenic, and knock-out mouse models of male reproductive defects developed by Program Project investigators provide a significant and critical resource for eventual clinical translation. To correlate clinical features of male infertility with new discoveries at the molecular level, to better understand the disease processes and thereby develop new and more effective treatment and diagnostic modalities. The expertise of this multidisciplinary group of scientists working together is expected to yield new understandings of the basic pathophysiology of male infertility.