FERTILIZATION DYSFUNCTION AND HUMAN MALE INFERTILITY

受精功能障碍和人类男性不育症

• 批准号: 3316964
• 负责人: NICHOLAS L CROSS
• 金额: $ 9.38万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3316964
• 关键词: N acetylglucosamine; acrosome; antibody; cell membrane; chemical binding; egg /ovum; electron microscopy; fertility; fertilization; galactosyltransferases; gel electrophoresis; human subject; immunofluorescence technique; male; sperm; sperm capacitation; sugar nucleotide

Most cases of male infertility can not be adequately explained although some are thought to involve fertilization dysfunction. Our objective is to understand the cell and molecular biology of one of the first stages of the human fertilization process - the early association of the sperm with the egg's zona pellucida - and to determine if there is a class of male infertility resulting from dysfunction of this stage of gamete interaction. The proposed experiments will test with human gametes a model developed from animal studies which suggests sperm-zona binding is due to bonds formed between an externally exposed, plasma membrane sperm enzyme (galactosyltransferase) and terminal N-acetylglucosamine residues in the zona pellucida. In pilot experiments, we have detected galactosyltransferase on human sperm. In this project we will test the role of this enzyme in the binding of sperm to the human zona pellucida by determining: 1) the effectiveness of inhibitors of the enzyme in blocking sperm-zona binding, 2) the ability of the human zona pellucida to serve as an acceptor for sperm galactosyltransferase-catalyzed transfer of [3H]-galactose from uridinediphospho[3H]galactose and 3) the ability of uridinediphosphogalactose to cause detachment of sperm bound to the human zona pellucida. The incidence of subnormal sperm-zona binding in infertile men will be reinvestigated using an assay of increased precision, and the correlation between the sperm-zona binding and sperm galactosyltransferase activity will be determined in both fertile and infertile men, to see if subnormal sperm transferase activity can be used as an indicator of infertility. Finally, the major protein components of the human zona pellucida will be analyzed by SDS/polyacrylamide gel electrophoresis. A solubilized preparation of human zonae pellucidae will be tested for its ability to induce acrosome reactions in human sperm and to see if it contains material with properties expected of a sperm receptor.

大多数男性不育病例不能充分解释 人们认为有些涉及受精的功能障碍。 我们的目标是 了解第一阶段之一的细胞和分子生物学 人类受精过程 - 精子的早期关联与 鸡蛋的Zona pellucida-并确定是否有一类男性 该配子阶段的功能障碍引起的不孕症 相互作用。 拟议的实验将与人配子测试模型 从动物研究中开发的，这表明精子 - 佐纳结合是由于 外部暴露的质膜精子酶之间形成的键 （半乳糖基转移酶）和末端N-乙酰葡萄糖在该中的N-乙酰葡萄糖残基 Zona Pellucida。 在试点实验中，我们已经检测到 人类精子上的半乳糖基转移酶。 在这个项目中，我们将测试 该酶在精子与人Zona Pellucida的结合中的作用 确定：1）酶抑制剂在阻塞中的有效性 精子 - 佐纳结合，2）人类Zona Pellucida的能力 精子半乳糖基转移酶催化转移的受体 [3H] - 乌里德尼磷[3H]半乳糖和3）的乳糖果和3） UridinedIphosphogalacosos造成与人结合的精子的脱离 Zona Pellucida。 不育的精子亚zona结合的发生率 男性将使用精确度提高的测定法对男人进行重新研究，并且 精子 - 佐纳结合与精子半乳糖基转移酶之间的相关性 活动将在肥沃的男性和不育男人中确定，以查看是否是否 亚正常的精子转移酶活性可以用作指标 不育。 最后，人Zona的主要蛋白质成分 SDS/聚丙烯酰胺凝胶电泳将分析甲木菌。 一个 将测试人叶颗粒的溶解化制剂 能够在人类精子中诱导Acrosom反应并查看它是否是否 包含具有精子受体预期的特性的材料。