Hurtt M E, Zenick H
Fundam Appl Toxicol. 1986 Aug;7(2):348-53. doi: 10.1016/0272-0590(86)90165-x.
Current test strategies for assessing male reproductive toxicity may be inadequate for estimating risk in humans. High levels of sperm production and existence of large epididymal sperm reserves in most test species may impede the detection of spermatotoxicity at low doses. The current report reflects initial efforts to address these issues. An active schedule of copulation was employed to reduce cauda epididymal reserves in the rat. The detection of spermatotoxicity in this animal relative to its nonmated counterpart was then compared following exposure to ethoxyethanol (EE). Adult, male Long-Evans hooded rats were assigned to a "mate" or "nonmate" condition, with the former mated every other day (3-hr sessions) for 2 weeks prior to and then throughout the experiment. After 2 weeks, males from each group were randomly assigned to receive either 0, 150, or 300 mg/kg (po) of EE, 5 days/week for 6 weeks. Males were then sacrificed and organ weights, testicular spermatid counts, and cauda epididymal sperm count and sperm morphology were obtained. EE produced a significant reduction in testicular weight and spermatid counts in mated and nonmated animals receiving 300 mg/kg. Significant decreases were also noted in epididymal sperm count and percentage normal morphology. However, these effects were seen in the nonmated animals only at 300 mg/kg, whereas significant reductions in both parameters were also obtained at 150 mg/kg in the males mated bidaily. The data from this study suggest that bidaily matings, by reducing epididymal sperm reserves, can enhance the detection of spermatotoxicity.
目前用于评估雄性生殖毒性的测试策略可能不足以估计人类的风险。大多数测试物种中精子产量高以及附睾中存在大量精子储备可能会妨碍低剂量下精子毒性的检测。本报告反映了为解决这些问题所做的初步努力。采用积极的交配计划来减少大鼠附睾尾部的储备。然后在暴露于乙氧基乙醇（EE）后，比较该动物与其未交配对应物的精子毒性检测情况。成年雄性长 Evans 戴帽大鼠被分配到“交配”或“未交配”组，前者在实验前 2 周及整个实验过程中每隔一天（3 小时时段）交配一次。2 周后，每组雄性大鼠被随机分配接受 0、150 或 300 mg/kg（口服）的 EE，每周 5 天，共 6 周。然后处死雄性大鼠，获取器官重量、睾丸精子细胞计数以及附睾尾部精子计数和精子形态。EE 使接受 300 mg/kg 的交配和未交配动物的睾丸重量和精子细胞计数显著降低。附睾精子计数和正常形态百分比也有显著下降。然而，这些影响仅在接受 300 mg/kg 的未交配动物中出现，而在每天交配两次的雄性动物中，150 mg/kg 时这两个参数也有显著降低。这项研究的数据表明，通过减少附睾精子储备，每天交配两次可以增强对精子毒性的检测。
