Apostoli P, Kiss P, Porru S, Bonde J P, Vanhoorne M
Institute of Occupational Health, University of Brescia, Italy.
Occup Environ Med. 1998 Jun;55(6):364-74. doi: 10.1136/oem.55.6.364.
To critically review the literature on male reproductive toxicity of lead in animals and humans.
A systematic literature search identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents. The studies were evaluated by paying attention mainly to sample size, study design, exposure, and dose characterisation, analytical method standardisation, and quality assurance.
Several studies on rats and other rodents indicated that blood lead concentrations > 30-40 micrograms/dl were associated with impairment of spermatogenesis and reduced concentrations of androgens. However, other animal studies, mainly about histopathological, spermatozoal, and hormonal end points, indicated that certain species and strains were quite resistant to the reproductive toxicity of lead and that different testicular lead concentrations could account for these differences. The human studies focused mainly on semen quality, endocrine function, and birth rates in occupationally exposed subjects, and showed that exposure to concentrations of inorganic lead > 40 micrograms/dl in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology. No relevant effects were detected on endocrine profile.
Several factors make it difficult to extrapolate the animal data to the human situation. The difficulties are mainly due to differences between species in reproductive end points and to the level of exposure. Concentrations of blood lead > 40 micrograms/dl seemed to be associated with a decrease in sperm count, volume, motility, and morphological alterations and a possible modest effect on endocrine profile. Dose-response relation, in particular at a threshold level, is poorly understood, and site, mode, or mechanism of action are unknown. Also, the effects were not always the same or associated in the same on sperm count and concentration. Some methodological issues and indications for future studies are discussed.
批判性地回顾关于铅对动物和人类雄性生殖毒性的文献。
系统的文献检索共确定了32项动物实验研究、22项流行病学研究、1例人类病例报告以及5篇综述文章或文献。主要通过关注样本量、研究设计、暴露情况、剂量特征、分析方法标准化和质量保证来评估这些研究。
多项关于大鼠和其他啮齿动物的研究表明,血铅浓度>30 - 40微克/分升与精子发生受损及雄激素浓度降低有关。然而,其他动物研究(主要涉及组织病理学、精子和激素终点指标)表明,某些物种和品系对铅的生殖毒性具有相当的抗性,且不同的睾丸铅浓度可解释这些差异。人类研究主要关注职业暴露人群的精液质量、内分泌功能和出生率,结果显示,血液中无机铅浓度>40微克/分升的暴露会通过降低精子数量、体积和密度,或改变精子活力和形态来损害男性生殖功能。未检测到对内分泌谱有相关影响。
有几个因素使得难以将动物数据外推至人类情况。这些困难主要源于不同物种在生殖终点指标上的差异以及暴露水平。血铅浓度>40微克/分升似乎与精子数量、体积、活力的降低以及形态改变有关,并且可能对内分泌谱有一定程度的影响。剂量 - 反应关系,尤其是阈值水平的关系,了解甚少,作用部位、方式或机制尚不清楚。此外,精子数量和浓度的影响并不总是相同或相关。本文讨论了一些方法学问题以及对未来研究的建议。