Molecular Basis of Male Infertility

描述(由申请人提供)：本申请寻求支持在贝勒医学院继续实施由NICHD资助的P01项目，利用最先进的遗传学研究男性不育。该计划项目的核心是一个核心管理单位，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是人类非梗阻性无精子症的DNA修复缺陷及其对卵胞浆内单精子注射(ICSI)受孕儿童的影响、睾丸中精原细胞增殖的分子控制、导致活力的基因缺陷以及精子-卵子相互作用缺陷。这些项目将受益于组织采购/分子技术核心，用于分析来自有生育能力和不育男子的大量人体样本，以便快速将基本研究成果转化为临床。该提案的总体目标仍然是：继续开展男性不育研究项目奖，为来自泌尿外科、产科和妇科、分子和细胞生物学、病理学和分子人类遗传学系的基础和临床科学家建立密切的工作关系。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专注于男性不育。创建一个组织采购/分子技术设施，向研究人员提供具有良好特征的可生育和不育男子的组织，以迅速将基本研究成果转化为临床领域。由计划项目调查员开发的自发的、转基因的和敲除的雄性生殖缺陷小鼠模型为最终的临床翻译提供了重要的和关键的资源。将男性不育的临床特征与分子水平上的新发现联系起来，以更好地了解疾病过程，从而开发更有效的新的治疗和诊断方法。这个多学科的科学家小组共同工作的专业知识有望对男性不育的基本病理生理学产生新的理解。

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.