Molecular characterization of unique recognition sites on the surface of human spermatozoa

了解调节人类精子功能的分子机制对于男性不育的临床治疗、试图开发新的男性避孕方法和将转基因引入男性生殖系的策略是至关重要的。精子功能缺陷是人类不育的最大单一原因。尽管这种情况很普遍，但我们不知道大多数男性不育病例是如何发生的，在绝大多数患者中，我们也不知道精子生化的哪个特定方面存在缺陷。因此，我们一直无法为不育男性开发出敏感的生化诊断测试，也没有任何合理的治疗方法来解决这种情况的原因。同样，自输精管结扎术以来，尽管在女性避孕领域取得了重大进展，但没有采用任何新的男性生育调节方法。显然，如果我们要开发诊断精子功能缺陷的敏感方法，引入治疗和预防男性不育的方案，并发现男性避孕的新方法，我们必须首先了解使这些高度专门化的细胞发挥其独特功能的细胞机制。在这项研究中，我们将重点研究精子功能最重要的属性之一，即这些细胞识别卵子的能力。一旦了解了这一基本识别过程的生化基础，就应该为针对这一信号系统的临床应用的开发铺平道路，这将涉及一系列学科，包括生殖毒理学、职业医学、计划生育、不孕症和生物技术。

Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do we understand which particular aspect of sperm biochemistry is defective. As a consequence we have not been able to develop sensitive biochemical diagnostic tests for the infertile male nor do we have any rational methods of treatment that address the cause of this condition. Similarly no new methods of male fertility regulation have been introduced since vasectomy despite the major advances that have been made in the field of female contraception over the same period of time. Clearly if we are to develop sensitive methods for the diagnosis of defective sperm function, introduce protocols for the treatment and prevention of male infertility and discover novel approaches to male contraception, we must first understand the cellular mechanisms that enable these highly specialized cells to perform their unique function. In this study we shall focus on one of the most important attributes of sperm function the capacity of these cells to recognize the egg. Once the biochemical basis of this fundamental recognition process is understood, it should pave the way for the development of clinical applications that target this signaling system with implications for a range of disciplines including reproductive toxicology, occupational medicine, family planning, infertility and biotechnology.