SPERM ZONA ACCEPTOR--ENVIRONMENTAL EFFECTS

人类精子甘露糖凝集素最近被确定为一种生化物质 精子与人类卵子结合的能力的标志 顶体反应。它在精子表面的表达取决于 质膜成分的变化。在这个项目中，我们将研究 重金属和氧化剂对人基因表达的影响 精子甘露糖凝集素。本项目由三项研究组成。[L]A 对90-125名有记录的工人进行的前瞻性病例对照研究 金属加工的职业性暴露。精液和血液样本，采集 入职前和入职一年后，将进行毒物水平检测， 由毒物作用产生的物种的内分泌参数和水平 细胞膜。生育率水平和混杂变量的影响 将通过问卷调查进行评估。中的变化将与正常进行比较 100名年龄频率匹配、未暴露于 确定重要性。[2]对其作用的体外研究 100名有生育能力的男性精子上的毒物。剂量-反应曲线将是 由单个样品的重复等分生成。毒物含量 将评估损害以探索毒物的分子机制 效果。这项研究的初步数据构成了这项应用的一部分。 [3]对环境中暴露于这些相同毒物的调查，使用50- 100名精子正常不育的男性，每个人的年龄频率也与 有生育能力的男性控制组。单一的血液和精子样本将从 所有受试者和相同的参数被检测。 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 会影响人类精子甘露糖凝集素的表达并降低生育力。 阐明这些毒物作用的分子机制 人类精子甘露糖凝集素的表达及其对男性生育能力的影响[c] 测定甘露糖凝集素缺陷的正常精子症不育男性 表情，但没有职业暴露，在以下方面与生育能力强的男性不同 血液或精液中金属相关毒物的水平，或者他们的精子 膜成分的不同使它们更容易 损伤，以及[d]表明甘露糖凝集素表达检测是一种 评估潜在毒物危害的快速、非侵入性方法 提供给人类男性繁殖力，并评估损害的程度 在职业或环境暴露后。

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.