FERTILIZATION DYSFUNCTION AND HUMAN MALE INFERTILITY

大多数男性不育症的病例不能充分解释， 有些被认为与受精功能障碍有关。 我们的目标是 了解细胞和分子生物学的第一阶段之一， 人类受精过程-精子与精子的早期结合 卵的透明细胞--为了确定是否有一类雄性 由于这一阶段配子功能障碍而导致的不育 互动 拟议中的实验将用人类配子测试一种模型， 从动物研究中发现，精子与精子的结合是由于 一种暴露在外的质膜精子酶 （半乳糖基转移酶）和末端N-乙酰葡糖胺残基 透明的 在试点实验中，我们发现 半乳糖基转移酶 在这个项目中，我们将测试 该酶在精子与人类透明带结合中的作用 确定：1）酶抑制剂在阻断 精子结合，2）人类透明细胞作为 精子半乳糖基转移酶催化转移的受体， [3 H]-半乳糖从尿苷二磷酸[3 H]半乳糖和3）的能力， 尿苷二磷酸半乳糖导致与人结合的精子脱离 透明的 不育症患者精子结合功能低下的发生率 男性将使用更高精度的检测方法进行重新调查， 精子结合率与精子半乳糖基转移酶的相关性 活性将在生育和不育男性中测定，以观察是否 低于正常的精子转移酶活性可用作 不孕 最后，人体骨骼肌的主要蛋白质成分 将通过SDS/聚丙烯酰胺凝胶电泳分析透明质酸。 一 将测试人透明带的溶解制剂的 在人类精子中诱导顶体反应的能力， 含有预期具有精子受体特性的材料。

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.