Toxicology Department, Cinvestav, Ave. IPN 2508, Colonia Zacatenco, Mexico City, 07360, Mexico.
Physiology, Biophysics and Neurosciences Department, Cinvestav, Ave. IPN 2508, Colonia Zacatenco, Mexico City, 07360, Mexico.
Toxicology. 2020 May 30;438:152463. doi: 10.1016/j.tox.2020.152463. Epub 2020 Apr 12.
Methyl parathion (Me-Pa) is an extremely toxic organophosphorus pesticide still used in developing countries. It has been associated with decreased sperm function and fertility and with oxidative and DNA damage. The blood-testis barrier (BTB) is a structure formed by tight junction (TJ) proteins in Sertoli cells and has a critical role in spermatogenesis. We assessed the effect of repeated doses of Me-Pa (3-12 mg/kg/day for 5 days, i.p.) on sperm quality, lipid oxidation, DNA integrity, and BTB permeability in adult male mice and explored oxidation as a mechanism of toxicity. Me-Pa caused dose-dependent effects on sperm quality, lipoperoxidation, and DNA integrity. Testis histology results showed the disruption of spermatogenesis progression and atrophy of seminiferous tubules. The pesticide opened the BTB, as evidenced by the presence of a biotin tracer in the adluminal compartment of the seminiferous tubules. This effect was not observed after 45 days of exposure when a spermatogenic cycle had completed. The coadministration of the antioxidant α-tocopherol (50 mg/kg/day for 5 days, oral) prevented the effects of Me-Pa on sperm quality, DNA and the BTB, indicating the importance of oxidative stress in the damage generated by Me-Pa. As evidenced by immunochemistry, no changes were found in the localization of the TJ proteins of the BTB, although oxidation (carbonylation) of total proteins in testis homogenates was detected. Our results show that Me-Pa disturbs the BTB and that oxidation is involved in the observed toxic effects on sperm cells.
甲基对硫磷（Me-Pa）是一种剧毒有机磷农药，仍在发展中国家使用。它与精子功能和生育能力下降以及氧化和 DNA 损伤有关。血睾屏障（BTB）是由支持细胞中的紧密连接（TJ）蛋白形成的结构，在精子发生中起着关键作用。我们评估了重复给予甲基对硫磷（3-12 mg/kg/天，腹腔注射，共 5 天）对成年雄性小鼠精子质量、脂质氧化、DNA 完整性和 BTB 通透性的影响，并探讨了氧化作为毒性机制。Me-Pa 对精子质量、脂质过氧化和 DNA 完整性产生了剂量依赖性影响。睾丸组织学结果显示精子发生进展中断和曲细精管萎缩。该农药破坏了 BTB，因为在曲细精管的腔侧隔室中存在生物素示踪剂。当完成一个精子发生周期时，在 45 天的暴露后未观察到这种作用。抗氧化剂α-生育酚（50 mg/kg/天，口服，共 5 天）的共同给药可防止 Me-Pa 对精子质量、DNA 和 BTB 的影响，表明氧化应激在 Me-Pa 产生的损伤中很重要。免疫化学证据表明，尽管在睾丸匀浆中检测到总蛋白的氧化（羰基化），但 BTB 的 TJ 蛋白的定位没有变化。我们的结果表明，Me-Pa 扰乱了 BTB，氧化参与了观察到的对精子细胞的毒性作用。
