COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK

我们的总体目标是改善男性和女性的生殖健康，从而促进健康和想要的儿童的出生。该应用程序的目标是成为合作多中心生殖医学网络(CMRMN)的一部分。我们致力于合作研究，并提供庞大的患者基础(包括异常高的少数族裔比例)，以便将受试者登记到网络协议中。为了实现这一目标，我们建议通过以下方式实现这一目标：证明韦恩州立大学的研究专业知识和资源范围与成功参与该网络一致；通过提供韦恩州立大学在合作临床研究方面的承诺和记录的证据；并通过提供一个“概念”方案作为我们构思和设计合作项目的能力的证明。我们的期望是，在其他成员确定的研究中，我们将成为CMRMN不可或缺的和有贡献的成员，并成为新项目的创新者。特别是，我们将在全基因组范围内筛选可以解释生殖异常发病机制的遗传差异。我们的长期研究目标之一是确定男性不育的先天和后天遗传原因，以便为考虑将辅助生殖技术作为解决不育问题的解决方案的受影响夫妇提供高度特异性的咨询和/或治疗。我们的概念方案的具体目标是通过微阵列技术的创新应用来识别与男性因素不育密切相关的基因。这项研究的中心假设是，与有生育能力的男性相比，不育男性精子中包含的基因转录本(信使核糖核酸物种)在质量和数量上都会有所不同，从而能够识别出候选的“不育基因”。其基本原理是，一旦通过合作的全基因组筛选确定了候选基因，就可以进行假设驱动的研究，以确定它们是否与一种或多种男性因素不育症的遗传形式偶然相关。我们将通过追求两个具体目标来检验我们的中心假设：1)确定可生育男性精子中基因转录本的差异程度；2)确定与可生育男性相比，不育男性精子中表达不同的基因转录本。CMRMN对于成功完成议定书至关重要；它将确保准确解释结果所需的权力。拟议的转译研究具有创新性，因为它将临床和基础分子遗传学专业知识结合在一起，合作将使用新的分析(微阵列)技术，以经济高效的方式获得男性因素不育的遗传原因线索。结果将是重要的，因为它们将为最终分析对男性生育力产生负面影响的遗传因素提供基础，从而导致对男性因素不育症的遗传原因进行高精度、廉价的诊断测试，在某些情况下，允许开出特定的替代疗法处方。

Our overall goal is to improve the reproductive health of men and women, thereby fostering the birth of healthy and wanted children. The objective of this application is to become part of the Cooperative Multicenter Reproductive Medicine Network (CMRMN). We are committed to cooperative research and offer a large patient base (including an unusually high percentage of minorities) from which to enroll subjects into Network protocols. We propose to achieve this objective by documenting that Wayne State's spectrum of research expertise and resources is consistent with successful participation in the Network; by providing evidence of Wayne State's commitment and track record in cooperative clinical research; and by providing a 'concept' protocol as proof of our ability to conceive and design a cooperative project. It is our expectation that we would be an integral and contributing member of the CMRMN in research identified by other members, and as an innovator of new projects. In particular, we would contribute to genome-wide screening for genetic differences that could explain the pathogenesis of reproductive abnormalities. One of our long-range research goals is to identify congenital and acquired genetic causes of male infertility, so that highly specific counseling and/or therapy can be offered to affected couples considering assisted reproductive technologies as a solution to infertility. The specific objective of our concept protocol is to identify genes, through the innovative application of microarray technology, closely associated with male factor infertility. The central hypothesis for the proposed research is that gene transcripts (mRNA species) contained in the sperm of infertile males will differ qualitatively and quantitatively, compared to those of fertile men, thereby allowing candidates for 'infertility genes' to be identified. The rationale is that once candidate genes have been identified by cooperative genome-wide screening, hypothesis-driven research can be formulated to determine whether they relate casually to one or more genetic forms of male factor infertility. We will test our central hypothesis by pursuing two specific aims: 1) identify the extent to which the profile of gene transcripts varies in the sperm of fertile males; and 2) identify gene transcripts that are expressed differently in the sperm of infertile, compared to fertile, men. The CMRMN is vital to successful completion of the protocol; it will assure the power needed to interpret results accurately. The proposed translational research is innovative because it combines clinical and basic molecular genetic expertise in a cooperative effort that will employ new analytical (microarray) technology to cost- effectively obtain clues to the genetic causes of male factor infertility. The outcomes will be significant because they will provide the foundations for definitive analysis of genetic factors that negatively affect male fertility, thereby leading to highly accurate, inexpensive diagnostic tests for genetic causes of male factor infertility, and in some cases, allow the prescription of specific replacement therapy.