Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Int J Mol Sci. 2022 Apr 11;23(8):4220. doi: 10.3390/ijms23084220.
Mebendazole (MBZ) is a synthetic benzimidazole known for its antiparasitic properties. In recent years, growing evidence showed that MBZ was also used as an anti-tumor agent. However, whether (and to what extent) this drug treatment affected the male reproductive system was not well-understood. In this study, male C57BL/6 mice were injected with 40 mg/kg/day of MBZ. The treatment was for 3 and 7 days. Our results showed that the injected mice exhibited an abnormal spermatogenic phase with a significant decrease in sperm. We further detected microtubule disruption and transient functional destruction of the blood-testes barrier (BTB) in the MBZ-injected mice testes (BTB). Our data confirmed that MBZ suppressed the expression of the BTB junction-associated proteins and disrupted the Sertoli cells' function in vivo. Moreover, MBZ-treated mice demonstrated an aberrant caspase-3 signalling pathway, which resulted in the apoptosis of the germ cells. Here, we present our data, indicating that MBZ impairs BTB by reducing the expression of the microtubules' and BTB junction-associated proteins. The last leads to activating the caspase-3 pathway, which triggers extensive germ cell apoptosis.
苯并咪唑（MBZ）是一种合成的苯并咪唑，具有抗寄生虫特性。近年来，越来越多的证据表明，MBZ 也被用作抗肿瘤药物。然而，这种药物治疗是否（以及在何种程度上）影响男性生殖系统尚不清楚。在这项研究中，雄性 C57BL/6 小鼠每天注射 40mg/kg 的 MBZ。处理时间为 3 天和 7 天。我们的结果表明，注射的小鼠表现出异常的精子发生阶段，精子数量显著减少。我们进一步检测到微管的破坏和 MBZ 注射小鼠睾丸中短暂的血睾屏障（BTB）功能破坏。我们的数据证实 MBZ 抑制了 BTB 连接相关蛋白的表达，并在体内破坏了支持细胞的功能。此外，MBZ 处理的小鼠表现出异常的半胱天冬酶-3 信号通路，导致生殖细胞凋亡。在这里，我们展示了我们的数据，表明 MBZ 通过降低微管和 BTB 连接相关蛋白的表达来损害 BTB。最后导致激活半胱天冬酶-3 通路，触发广泛的生殖细胞凋亡。
