Functional Genomic Approach to Male Contraception

现代避孕方法的历史短得令人惊讶，主要是由几种方法， 如女性口服避孕药或男性避孕套等物理屏障方法。尽管 由于缺乏方法选择，研究表明，男子渴望在生育率调节方面发挥更大作用。 过去的一些努力集中在男性避孕药的开发上， 激素和免疫控制精子发生，但很少有研究集中在发展一个 一种男性避孕药，它将改变调节精子发生的关键基因的活性。这是 我们所描述的方法。这是一个及时的方法，正如人类基因组计划的完成和 对于那些模式生物，我们对基因和蛋白质有着前所未有的了解，这些基因和蛋白质可能会 控制精子的发育。在我们的初步研究中，我们已经确定了编码雄性的基因， 果蝇中的生育因子，在小鼠和人类中发现了同源物，并开始探索机制 通过检查不育突变果蝇和基因敲除小鼠的表型来研究雄性不育。的目标 本研究旨在鉴定和表征与男性生育力调节有关的新基因靶点。 并为针对这些目标开发男性避孕药具奠定基础。我们将筛选 通过我们的比较基因组学鉴定雄性生殖基因的小鼠ES基因诱捕细胞文库 分析，以产生破坏保守的雄性育性因子的小鼠敲除突变体，以表征 这些关键调节因子在精子产生和成熟过程中的作用，并最终提供一种资源， 雄性生殖突变体，供避孕领域和生殖领域的研究人员使用。

Modern contraceptive methods have a surprisingly short history and are dominated by a few methods such as the oral contraceptive pill for women or physical barrier methods such as condoms for men. In spite of the lack of choice of methods, studies show that men aspire to play a greater role in the regulation of fertility. Some effort in the past has been focused on development of male contraceptives which focused on hormonal and immunological control of spermatogenesis, but few studies have focused on developing a male contraceptive that will alter the activity of key genes that regulate spermatogenesis. This is the approach that we outline. It is a timely approach, as with the completion of the human genome project and those of model organisms, we have unprecedented knowledge of the genes and proteins that are likely to govern the development of sperm. In our preliminary studies, we have identified genes that encode male fertility factors in Drosophila, discovered homologs in mice and humans, and begun to explore mechanisms of male infertility by examining the phenotypes of sterile mutant flies and knockout mice. The objectives of this research are to identify and to characterize novel gene targets involved in the regulation of male fertility and to lay the ground work for the development of male contraceptives against those targets. We will screen mouse ES gene trap cell library for male reproductive genes identified through our comparative genomics analysis, to generate mouse knockout mutants disrupting the conserved male fertility factors, to characterize the roles of those key regulators during sperm production and maturation, and finally to provide a resource of male reproductive mutants for researchers in the contraceptive field as well as in the reproductive field.