Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.
Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
Environ Toxicol. 2018 Jul;33(7):711-719. doi: 10.1002/tox.22556. Epub 2018 Apr 19.
Fine particle matter (PM) is correlated with male reproductive dysfunction in animals and humans, but the underlying mechanisms remain unknown. To investigate the toxic mechanism of PM, 32 male Sprague-Dawley (SD) rats were exposed to saline or PM with the doses of 1.8, 5.4, and 16.2 mg/kg.b.w. via intratracheal instillation, respectively, one time every 3 days, in total times for 30 days. Sperm concentration, hormone level, the expressions of BTB-associated protein and the mitogen-activated protein kinase (MAPK) pathway, tumor necrosis factor α and transforming growth factor β3 levels were detected. The results showed a decrease in sperm number, testosterone and luteinizing hormone levels and altered ultrastructure of BTB in testis of rat after exposure to PM . The protein levels of N-Cadherin, Occludin, Claudin-11, and Connexin-43 were significantly decreased in the testes. TGF-β3 content in testes showed increase, with the p-p38/p38 MAPK ratio also increasing after PM exposure. These results demonstrate that PM restrained the expressions of BTB-associated proteins through activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion, and therefore lead to the damage of BTB resulting in the decrease of sperm quality, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.
细颗粒物 (PM) 与动物和人类的男性生殖功能障碍有关,但潜在机制尚不清楚。为了研究 PM 的毒性机制,将 32 只雄性 Sprague-Dawley (SD) 大鼠通过气管内滴注分别暴露于生理盐水或 PM 中,剂量分别为 1.8、5.4 和 16.2mg/kg.b.w.,每 3 天一次,共 30 天。检测精子浓度、激素水平、紧密连接相关蛋白和丝裂原活化蛋白激酶 (MAPK) 通路、肿瘤坏死因子α和转化生长因子β3 水平的表达。结果显示,暴露于 PM 后,大鼠睾丸中的精子数量、睾酮和促黄体生成素水平下降,BTB 的超微结构发生改变。睾丸中 N-Cadherin、Occludin、Claudin-11 和 Connexin-43 的蛋白水平显著降低。TGF-β3 含量在暴露 PM 后增加,p-p38/p38 MAPK 比值也增加。这些结果表明,PM 通过激活 TGF-β3/p38 MAPK 通路和降低睾酮分泌来抑制 BTB 相关蛋白的表达,从而导致 BTB 的损伤,导致精子质量下降,这可能是其对精子发生和男性生殖产生负面影响的潜在原因。