Objectives: Exposure to 4-vinylcyclohexene diepoxide (VCD) was reported to induce testicular germ cell toxicity in rodents. However, there is paucity of information on the precise biochemical and molecular mechanisms of VCD-induced male reproductive toxicity.

Methodology: This study investigated the influence of VCD on testicular and epidydimal functions following oral exposure of Wistar rats to VCD at 0, 100, 250 and 500 mg/kg for 28 consecutive days.

Results: Administration of VCD significantly decreased the body weight gain and organo-somatic indices of the testes and epididymis. When compared with the control, VCD significantly decreased superoxide dismutase and catalase activities in the testes whereas it significantly decreased superoxide dismutase activity but increased catalase activity in the epididymis. Moreover, while glutathione peroxidase activity and glutathione level remain unaffected, exposure of rats to VCD significantly increased glutathione S-transferase activity as well as hydrogen peroxide and malondialdehyde levels in testes and epididymis of the treated rats. The spermiogram of VCD-treated rats showed significant decrease in epididymal sperm count, sperm progressive motility, testicular sperm number and daily sperm production when compared with the control. Administration of VCD significantly decreased circulatory concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone along with testicular and epididymal degeneration in the treated rats. Immunohistochemical analysis showed significantly increased cyclooxygenase-2, inducible nitric oxide synthase, caspase-9 and caspase-3 protein expressions in the testes of VCD-treated rats.

Conclusion: Exposure to VCD induces testicular and epidydimal dysfunctions via endocrine suppression, disruption of antioxidant enzymes activities, increase in biomarkers of oxidative stress, inflammation and apoptosis in rats.

目的：据报道，接触 4-乙烯基环己烯二环氧化合物 (VCD) 会诱发啮齿动物睾丸生殖细胞毒性。然而，关于 VCD 引起的男性生殖毒性的精确生化和分子机制的信息很少。

方法：本研究调查了 Wistar 大鼠连续 28 天口服暴露于 0、100、250 和 500 mg/kg 的 VCD 后，VCD 对睾丸和附睾功能的影响。

结果：服用 VCD 显着降低了体重增加以及睾丸和附睾的有机体指数。与对照组相比，VCD显着降低了睾丸中的超氧化物歧化酶和过氧化氢酶活性，而显着降低了附睾中的超氧化物歧化酶活性，但增加了过氧化氢酶活性。此外，虽然谷胱甘肽过氧化物酶活性和谷胱甘肽水平不受影响，但将大鼠暴露于VCD显着增加了治疗大鼠睾丸和附睾中的谷胱甘肽S-转移酶活性以及过氧化氢和丙二醛水平。与对照组相比，VCD治疗组大鼠的精子图显示，附睾精子数量、精子前行活力、睾丸精子数量和每日精子产量显着减少。给予 VCD 显着降低了治疗大鼠的卵泡刺激素、黄体生成素和睾酮的循环浓度，同时降低了睾丸和附睾的退化。免疫组织化学分析显示，VCD 治疗的大鼠睾丸中环氧合酶-2、诱导型一氧化氮合酶、caspase-9 和 caspase-3 蛋白表达显着增加。

结论：暴露于 VCD 会通过内分泌抑制、抗氧化酶活性破坏、氧化应激、炎症和细胞凋亡生物标志物增加而导致睾丸和附睾功能障碍。