SPERM ZONA ACCEPTOR--ENVIRONMENTAL EFFECTS

人精子甘露糖凝集素最近被确定为一种生物化学物质， 精子与人类卵子结合并经历一个 顶体反应它在精子表面的表达取决于 质膜组成的变化。在这个项目中，我们将研究 选择的重金属和氧化剂对人类表达的影响 精子甘露糖凝集素。 该项目由三项研究组成。[l)一 对90-125名有记录的工人进行的前瞻性病例对照研究 金属加工的职业暴露。采集精液和血液样本 就业前和一年后，将进行毒物水平测定， 内分泌参数和毒物作用产生的物种水平 细胞膜 生育水平和混杂变量的影响 将通过问卷进行评估。 将变化与正常值进行比较 100名年龄频率匹配的未暴露于 确定重要性。 [2)体外研究其作用 对100名有生育能力的男性的精子产生毒性。剂量-反应曲线如下： 由单个样品的一式两份等分试样生成。 毒物水平 将评估损伤以探索毒物的分子机制 方面的影响.本研究的初步数据构成本申请的一部分。 [3]使用50- 100个样本对这些有毒物质的环境暴露进行了调查， 100例正常精子不育男性，每例年龄频率匹配， 可育雄性对照。 将从以下人员中采集单个血液和精子样本： 测定所有受试者和相同参数。 这些研究的结果将包括：[a]确定血液和精液 与金属加工有关的金属和其他有毒物质的水平， 可影响人精子甘露糖凝集素表达，降低生育力[B] 阐明了这些毒物作用的分子机制， 人精子甘露糖凝集素表达和对人类男性生育力的影响，[c] 确定是否有甘露糖凝集素缺陷的正常精子不育男性 表达，但没有职业暴露，与有生育能力的男性不同， 血液或精液中金属相关毒物的水平，或者如果他们的精子 膜组合物的不同使它们更容易 损伤，和[d]证明甘露糖凝集素表达测定是一种 一种快速、非侵入性的方法来评估潜在有毒物质的危害， 目前人类男性生殖力，并评估损害的程度， 职业或环境暴露后。

Human sperm mannose lectin has recently been established as a biochemical marker for the ability of sperm to bind to human eggs and undergo an acrosome reaction. Its expression on the sperm surface depends upon changes in plasma membrane composition. In this project we will study effects of selected heavy metals and oxidants upon expression of human sperm mannose lectin. This project is composed of three studies. [l) A prospective, case-controlled study of 90-125 workers with documented occupational exposures from metalworking . Semen and blood samples, taken pre-employment and after one year, will be assayed for toxicant levels, endocrine parameters and levels of species created by toxicant action upon cellular membranes. Fertility levels and effects of confounding variables will be assessed by questionnaire. Changes in will be compared to normal variability among 100 age frequency-matched, unexposed fertile males to determine significance. [2) An in vitro study of effects of the same toxicants upon sperm of 100 fertile males. Dose-response curves will be generated from duplicate aliquots of single samples. Levels of toxicant damage will be assessed to probe the molecular mechanisms of toxicant effects. Preliminary data from this study forms part of this application. [3] A survey of environmental exposure to these same toxicants, using 50- 100 normo-spermic infertile males, each also age frequency-matched to fertile male controls. Single blood and sperm samples will be taken from all subjects and the same parameters assayed. Results of these studies will include: [a] establishing blood and semen levels of metals and other toxicants associated with metalworking which can affect human sperm mannose lectin expression and reduce fecundity, [b] elucidating molecular mechanisms underlying actions of these toxicants on human sperm mannose lectin expression and upon human male fertility, [c] determining if normospermic infertile men with defects in mannose lectin expression, but no occupational exposure, differ from fertile men in levels of metal-associated toxicants in blood or semen, or if their sperm membrane compositions differ in a way to render them more liable to damage, and [d) demonstrating that mannose lectin expression assays are a quick, non-invasive means of assessing the hazard that potential toxicants present to human male fecundity, and of assessing the extent of damage after occupational or environmental exposure.