Molecular Basis of Male Infertility

描述（由申请人提供）：本申请寻求支持继续在贝勒医学院NICHD资助的P01计划项目，使用最先进的遗传学研究男性不育症。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。本项目的研究重点是：人类非阻塞性无精子症的DNA修复缺陷及其对卵胞浆内单精子注射（ICSI）受孕的影响；睾丸中精原细胞增殖的分子控制；导致运动的基因缺陷和精子-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，用于分析来自可生育和不育男性的大量人类样本，以便快速临床转化基础研究成果。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，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的基础和临床科学家之间建立密切的工作关系。在一个项目中促进这些小组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。建立组织采购/分子技术设施，为研究人员提供来自可育和不育男性的良好特征组织，以快速将基础研究成果转化为临床领域。自发、转基因和基因敲除的雄性生殖缺陷小鼠模型由项目研究者开发，为最终的临床转化提供了重要和关键的资源。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，从而开发新的更有效的治疗和诊断方式。这个多学科小组的科学家共同努力的专业知识有望产生新的理解的基本病理生理的男性不育。

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.