Wyrobek A J, Gordon L A, Burkhart J G, Francis M W, Kapp R W, Letz G, Malling H V, Topham J C, Whorton M D
Mutat Res. 1983 May;115(1):1-72. doi: 10.1016/0165-1110(83)90014-3.
The literature on the mouse sperm morphology test and on other sperm tests in nonhuman mammals was reviewed (a) to evaluate the relationship of these tests to chemically induced spermatogenic dysfunction, germ-cell mutagenicity, and carcinogenicity, and (b) to make an interspecies comparison to chemicals. A total of 71 papers were reviewed. The mouse sperm morphology test was used to assess the effects of 154 of the 182 chemical agents covered. 4 other murine sperm tests were also used: the induction of acrosomal abnormalities (4 agents), reduction in sperm counts, (6 agents), motility (5 agents), and F1 sperm morphology (7 agents)). In addition, sperm tests for the spermatogenic effects of 35 agents were done in 9 nonmurine mammalian species; these included analyses for sperm count, motility, and morphology, using a large variety of study designs. For the mouse sperm morphology test, 41 agents were judged by the reviewing committee to be positive inducers of sperm-head shape abnormalities, 103 were negative, and 10 were inconclusive. To evaluate the relationship between changes in sperm morphology and germ cell mutagenicity, the effects of 41 agents on mouse sperm shape were compared to available data from 3 different mammalian germ-cell mutational tests (specific locus, heritable translocation, and dominant lethal). The mouse sperm morphology test was found to be highly sensitive to germ-cell mutagens; 100% of the known mutagens were correctly identified as positives in the sperm morphology test. Data are insufficient at present to access the rate of false positives. Although it is biologically unclear why one might expect changes in sperm morphology to be related to carcinogenesis, we found that (a) a positive response in the mouse sperm morphology test is highly specific for carcinogenic potential (100% for the agents surveyed), and (b) overall, only 50% of carcinogens were positive in the test (i.e., sensitivity approximately equal to 50%). Since many carcinogens do not produce abnormally shaped sperm even at lethal doses, negative findings with the sperm test cannot be used to classify agents as noncarcinogens. We conclude that the mouse sperm morphology test has potential use for identifying chemicals that induce spermatogenic dysfunction and perhaps heritable mutations. Insufficient numbers of chemicals agents have been studied by the other sperm tests to permit similar comparisons. A comparison of 25 chemicals tested with sperm counts, motility, and morphology in at least 2 species (including man, mouse and 9 other mammals) demonstrated good agreement in response among species. With further study, interspecies comparisons of chemically induced sperm changes may be useful for predicting and evaluating human effects.
对有关小鼠精子形态学试验以及非人类哺乳动物其他精子试验的文献进行了综述，目的如下：(a) 评估这些试验与化学物质诱导的生精功能障碍、生殖细胞致突变性和致癌性之间的关系；(b) 对不同物种对化学物质的反应进行比较。共查阅了71篇论文。在所涉及的182种化学物质中，有154种使用了小鼠精子形态学试验来评估其影响。还使用了其他4种小鼠精子试验：顶体异常诱导试验（4种化学物质）、精子计数减少试验（6种化学物质）、活力试验（5种化学物质）和F1代精子形态试验（7种化学物质）。此外，对35种化学物质在9种非小鼠哺乳动物物种中进行了精子发生效应的精子试验；这些试验包括使用多种研究设计对精子计数、活力和形态进行分析。对于小鼠精子形态学试验，评审委员会判定41种化学物质为精子头部形状异常的阳性诱导剂，103种为阴性，10种为不确定。为了评估精子形态变化与生殖细胞致突变性之间的关系，将41种化学物质对小鼠精子形状的影响与来自3种不同哺乳动物生殖细胞突变试验（特定位点、可遗传易位和显性致死）的现有数据进行了比较。发现小鼠精子形态学试验对生殖细胞诱变剂高度敏感；已知的诱变剂在精子形态学试验中100%被正确鉴定为阳性。目前尚缺乏足够数据来评估假阳性率。虽然从生物学角度尚不清楚为何会预期精子形态变化与致癌作用有关，但我们发现：(a) 小鼠精子形态学试验中的阳性反应对致癌潜力具有高度特异性（在所调查的化学物质中为100%）；(b) 总体而言，只有50%的致癌物在该试验中呈阳性（即敏感性约为50%）。由于许多致癌物即使在致死剂量下也不会产生形状异常的精子，因此精子试验的阴性结果不能用于将化学物质归类为非致癌物。我们得出结论，小鼠精子形态学试验在识别诱导生精功能障碍以及可能的遗传突变的化学物质方面具有潜在用途。通过其他精子试验研究的化学物质数量不足，无法进行类似比较。对至少2个物种（包括人类、小鼠和其他9种哺乳动物）进行精子计数、活力和形态检测的25种化学物质的比较表明，不同物种之间的反应具有良好的一致性。随着进一步研究，化学物质诱导的精子变化的种间比较可能有助于预测和评估对人类的影响。
