FACTORS AFFECTING SPERM FERTILITY

影响精子生育力的因素

• 批准号: 3316783
• 负责人: GABOR B HUSZAR
• 金额: $ 1.42万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3316783
• 关键词: adenosinetriphosphatase; bioenergetics; creatine kinase; creatine phosphate; fertility; flagellum; gel electrophoresis; human subject; isozymes; male reproductive system disorder; male reproductive system disorder diagnosis; mitochondria; sperm; sperm motility

This research project integrates our clinical and basic science interest, and is designed to identify objective biochemical measurements in sperm which are important in the prediction of fertiziling potential of male infertility patients. The proposed experiments are directed to sperm metabolism, and in part are designed based on the creatine phosphate shuttle hypothesis. This idea suggests a central role of creatine phosphate in energy transport, and the importance of creatine kinases in the mitochondria and flagellum of sperm in the synthesis and utilization of energy. We have found a correlation between the creatine kinase activity and the number of motile sperm in various specimens, and a statistically significant increase in creatine kinase and dynein ATPase (the principal structural protein and enzyme in sperm motility) activities of oligo/asthenospermic specimens. Furthermore, we demonstrated an enhancement of sperm velocity and motility index in response to creatine phosphate, and the presence of the mitochondrial type and brain type creatine kinase isozymes in human sperm. We also plan to perform chemical modifications of creatine kinase with fluorodinitrobenzene in live sperm, which will allow further quantification of creatine kinase in sperm, and may indicate the metabolic reserves available in various sperm specimens. With respect to structural proteins, we will quantify and determine the source of the unusual amino acid, 3-methylhistidine in sperm. Since this methylated amino acid has only been found so far in contractile proteins and excitable tissues, it may contribute to our understanding of the mechanism of sperm motility. The possible correlation between the biochemical measurements of creatine kinase and dynein ATPase activities, creatine kinase isozyme ratios, and between the conventional sperm analysis parameters (concentration, motility, velocity, and morphology) will aid in the evaluation and classification of the male infertility patients. We expect that this complex assessment of sperm function, combined with the fertility experience of the about 320 infertile couples in our intrauterine insemination program, will give us clear indication as to which of the parameters may be predictive to fertility/infertility. Thus, the proposed research project will introduce several new approaches in the diagnosis and treatment of male infertility patients.

该研究项目整合了我们的临床和基础科学兴趣， 并被设计用于识别精子中的客观生化测量 这对预测男性的生育潜力具有重要意义 不孕症患者 拟议中的实验是针对精子的 代谢，部分是基于磷酸肌酸设计的， 穿梭机假说 这个想法表明肌酸的核心作用 磷酸盐在能量运输中的作用，以及肌酸激酶在 精子的线粒体和鞭毛在精子合成和利用中的作用 能源 我们已经发现肌酸激酶活性与 和各种标本中活动精子的数量，以及统计学上的 肌酸激酶和动力蛋白ATP酶的显著增加（主要是 结构蛋白和酶）活性 少精/弱精标本。 此外，我们证明了一个 肌酸对精子运动速度和活力指数的影响 磷酸盐，以及线粒体型和脑型的存在 人精子肌酸激酶同工酶。 我们还计划进行化学 用氟代二硝基苯修饰活精子中的肌酸激酶， 这将允许进一步定量精子中的肌酸激酶， 可以指示各种精子标本中可用的代谢储备。 关于结构蛋白，我们将定量和确定 精子中不常见的氨基酸3-甲基组氨酸的来源。 由于这 甲基化的氨基酸迄今只在收缩蛋白中发现 和可兴奋组织，这可能有助于我们理解 精子运动机制 可能的相关性 肌酸激酶和动力蛋白ATP酶活性的生化测量， 肌酸激酶同功酶比值，并与常规精子分析 参数（浓度、运动性、速度和形态）将有助于 男性不育患者的评估和分类。 我们 预计这种复杂的精子功能评估，结合 对我院320对不孕夫妇的生育经验进行了总结 人工授精计划，将给我们明确的指示， 参数可以预测生育力/不育。 因此，拟议的 研究项目将介绍几种新的诊断方法， 治疗男性不育患者。