a Department of Biochemistry, Drug Metabolism & Toxicology Research Laboratories, College of Medicine , University of Ibadan , Ibadan , Nigeria.
Redox Rep. 2017 Nov;22(6):388-398. doi: 10.1080/13510002.2016.1259718. Epub 2016 Nov 28.
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.
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.
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.
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.
据报道，4-乙烯基环己烯二氧化物（VCD）暴露会导致啮齿动物睾丸生殖细胞毒性。然而，关于 VCD 诱导雄性生殖毒性的确切生化和分子机制的信息很少。
本研究通过 Wistar 大鼠连续 28 天口服 0、100、250 和 500mg/kg VCD，研究了 VCD 对睾丸和附睾功能的影响。
VCD 给药显著降低了体重增加和睾丸和附睾的器官体指数。与对照组相比，VCD 显著降低了睾丸中的超氧化物歧化酶和过氧化氢酶活性，而显著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，尽管谷胱甘肽过氧化物酶活性和谷胱甘肽水平不受影响，但 VCD 暴露显著增加了睾丸和附睾中谷胱甘肽 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 处理大鼠的精子谱显示附睾精子计数、精子前向运动、睾丸精子数和每日精子产量显著降低。VCD 给药显著降低了循环中卵泡刺激素、黄体生成素和睾酮的浓度，以及处理大鼠的睾丸和附睾退化。免疫组织化学分析显示，VCD 处理大鼠睾丸中环氧化酶-2、诱导型一氧化氮合酶、半胱天冬酶-9 和半胱天冬酶-3 蛋白表达显著增加。
VCD 暴露通过内分泌抑制、破坏抗氧化酶活性、增加氧化应激、炎症和细胞凋亡的生物标志物，导致大鼠睾丸和附睾功能障碍。
