Functional Genomic Approach to Male Contraception

现代避孕方法的历史令人惊讶地很短，主要由少数几种方法主导，如 作为口服避孕药的女性或身体屏障的方法，如避孕套的男性。尽管 缺乏方法的选择，研究表明，男性渴望在调节生育方面发挥更大的作用。 过去的一些努力集中在男性避孕药的开发上，其重点是 精子发生的激素和免疫控制，但很少有研究集中在发展一种 男性避孕药，将改变调节精子发生的关键基因的活性。这是 我们概述的方法。这是一种及时的方法，就像人类基因组计划和 对于那些模式生物，我们对可能导致 管理精子的发育。在我们的初步研究中，我们已经确定了编码男性的基因 果蝇中的生育因素，在老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，发现了男性不育的可能性。的目标 这项研究旨在识别和表征参与调节男性生育能力的新的基因靶点。 并为开发针对这些目标的男性避孕药奠定基础。我们会放映 我们比较基因组学鉴定的雄性生殖基因小鼠ES基因陷阱细胞文库 分析，产生小鼠基因敲除突变体，扰乱保守的男性生育因子，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，最终为精子提供 为避孕领域和生殖领域的研究人员提供男性生殖突变体。

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.