REGULATION AND CONTROL OF HUMAN SPERM MOTILITY

此应用程序的目标是确定生物化学基础 人类精子冷冻后运动能力的丧失 防止或扭转这一损失。我们将首先详细描述 新鲜射精和冷冻保存人的运动特性 一种新的完全计算机化的方法能够产生 头部和鞭毛波参数的“完整的运动轮廓”。 这项研究将首次完整地描述 冷冻保存对人精子活力的影响。测定生化指标 我们将为冷冻保存失去活力的基础提供第一个 人类精子活力是如何被调节的概述。要做到这一点，我们将 确定钙离子的作用和相互关系， 环磷酸腺苷、腺苷与“肌动素样运动”的磷酸化 蛋白质。所有研究都将在完整的精子中进行。我们会 重视核苷腺苷在启动过程中作用的研究 钙和环磷酰胺偶联作用在静止精子运动中的作用 AMP，腺苷通过精子外排的机制 核苷酸运输系统，以及它在细胞内的提升 腺苷脱氨酶抑制。这些研究可能会导致 开发一类新的化合物，腺苷脱氨酶抑制剂， 选择性地增加人类精子在精液中的活动密度。 我们将记录腺苷降低细胞内钙水平和 确定发生这种情况的机制。此外，我们还将 定义不同细胞内循环水平的独特影响 AMP和钙在完整的运动曲线上。这些研究将 文件HOE关键调控人类精子运动的多个 运动性参数，并将为描述 详细描述了冷冻保存过程中运动参数的变化。 确认丢失任何单个参数的基础将是 通过确定此参数的规则在 超低温保存。冷冻精子活力的恢复将是 通过返回冷冻精子中的细胞内信使来实现 对新鲜射精状态和防止运动功能丧失的使用 有选择性地保护运动部分的冷冻保护剂 机械设备在超低温保存过程中受损。

The goal of this application is to determine the biochemical basis for the loss of human sperm motility following cryopreservation and to prevent or reverse this loss. We will first characterize in detail the motility characteristics of freshly ejaculated and cryopreserved human sperm with a new fully computerized method capable of generating a "complete motility profile" of both head and flagellar wave parameters. This study will provide the first complete description of the effects of cryopreservation on human sperm motility. To determine the biochemical basis for loss of motility on cryopreservation we will provide the first overview of how human sperm motility is regulated. To do this we will determine the roles played by and interrelationships among calcium ion, cyclic AMP, adenosine and the phosphorylation of "axokinin-like motility proteins. All studies will be carried out in intact sperm. We will emphasize studies on the role of the nucleoside adenosine in initiating motility in immotile sperm by coupling the actions of calcium and cyclic AMP, the mechanism of efflux of adenosine efflux from sperm through a nucleotide transport system, and it intra-cellular elevation by adenosine deaminase inhibition. These studies may lead to the development of a new class of compounds, adenosine deaminase inhibitors, which selectively increase the motile density of human sperm in semen. We will document that adenosine lowers cytosolic calcium levels and determine the mechanism by which this takes place. Further, we will define the singular effects of varying intra-cellular levels of cyclic AMP and calcium on complete motility profiles. These studies will document hoe key regulators of human sperm motility control the multiple parameters of motility and will provide the basis for describing in detail the changes in motility parameters during cryopreservation. Confirmation of the basis for loss of any individual parameter will be obtained by determining how regulation of this parameter changes during cryopreservation. Recovery of motility in cryopreserved sperm will be carried out by returning intracellular messengers in cryopreserved sperm to their freshly ejaculated state and prevention of motility loss by use of cryoprotectants which selectively protect that part of the motility machinery damaged during cryopreservation.