COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK

协作多中心生殖医学网络

• 批准号: 6387740
• 负责人: Michael Peter Diamond
• 金额: $ 27.67万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-30 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6387740
• 关键词: assistive reproductive technique; clinical research; cooperative study; family planning; fertility; genetic mapping; genetic transcription; human subject; human therapy evaluation; male; microarray technology; sperm analysis

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.

我们的总体目标是改善男性和女人的生殖健康，从而促进健康和想要的孩子的诞生。 该应用的目的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，并提供大量的患者基础（包括异常高的少数族裔比例），从而将受试者纳入网络协议。我们建议通过记录韦恩州的研究专业知识和资源的范围来实现这一目标，这与成功参与网络一致。通过提供合作临床研究中韦恩州的承诺和往绩的证据；并提供“概念”协议作为我们受孕和设计合作项目的能力的证明。 我们期望我们成为其他成员确定的研究中CMRMN的组成部分，并且是新项目的创新者。特别是，我们将为全基因组筛查的遗传差异做出贡献，这些遗传差异可以解释生殖异常的发病机理。 我们的远程研究目标之一是确定先天性和获得的男性不育症遗传原因，以便可以将高度具体的咨询和/或治疗提供给考虑辅助生殖技术作为不孕症解决方案的受影响夫妇。 我们概念方案的具体目标是通过微阵列技术的创新应用与男性因素不育症密切相关。 拟议的研究的中心假设是，与肥沃的男性相比，不育男性精子中包含的基因转录物（mRNA种）将在定性和定量上有所不同，从而允许鉴定候选“不育基因”的候选者。 理由是，一旦通过合作基因组筛查确定了候选基因，就可以制定假设驱动的研究以确定它们是否随意地与一种或多种遗传形式的男性因子不育症相关。 我们将通过追求两个具体的目的来检验中心假设：1）确定基因转录物的特征在肥沃的雄性精子中的变化程度； 2）与肥沃的男性相比，在不育精子中确定不同表达的基因转录本。 CMRMN对于成功完成协议至关重要。它将确保准确解释结果所需的功率。 拟议的翻译研究具有创新性，因为它将临床和基本分子遗传专业知识与合作的努力结合在一起，该努力将采用新的分析（微阵列）技术来成本地获得有关男性不孕症遗传原因的线索。 结果将是重要的，因为它们将为对男性生育的负面影响的确定分析提供基础，从而导致高度准确，廉价的诊断测试，以实现男性因子不孕症的遗传原因，在某些情况下，允许处方特定的替代治疗。