REGULATION AND CONTROL OF HUMAN SPERM MOTILITY

本申请的目的是确定生物化学基础， 冷冻保存后人类精子活力的丧失， 防止或扭转这种损失。 我们将首先详细描述 新鲜精液和冷冻精液的运动特性 精子与新的完全计算机化的方法能够产生一个 头部和鞭毛波参数的“完整运动曲线”。 这项研究将首次完整描述 冷冻保存对人精子活力的影响 为了确定生物化学 我们将提供第一个冷冻保存丧失运动性的依据， 概述人类精子运动是如何调节的。 为此，我们将 确定了钙离子在其中所起的作用及相互关系， 环腺苷酸、腺苷与“轴激肽样运动”的磷酸化 proteins. 所有研究均在完整精子中进行。 我们将 强调研究核苷腺苷在启动 不动精子的运动力通过耦合钙和环 AMP，腺苷流出精子的机制，通过一个 核苷酸转运系统，它在细胞内升高， 腺苷脱氨酶抑制。 这些研究可能会导致 开发了一类新的化合物，腺苷脱氨酶抑制剂， 其选择性地增加精液中人类精子的活动密度。 我们将证明腺苷降低胞浆钙水平， 确定这种情况发生的机制。 此外，我们将 定义不同细胞内循环水平的奇异效应 AMP和钙对完整运动曲线的影响。 这些研究将 文件hoe人类精子运动的关键调节器控制多个 运动参数，并将提供基础， 详细说明了冷冻保存过程中运动参数的变化。 确认任何单个参数损失的依据将是 通过确定该参数的调节如何在 冷冻保存 冷冻保存的精子活力的恢复将是 通过在冷冻保存的精子中返回细胞内信使来进行 他们的新鲜射精状态和预防运动损失的使用 冷冻保护剂选择性地保护运动的那部分 冷冻保存过程中机器损坏。

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.