Decreasing epididymal sperm reserves enhances the detection of ethoxyethanol-induced spermatotoxicity

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.