The hazardous effects of herbicides are well known; however, their effects on the reproductive system remain unclear. In this study, we demonstrated the anti-proliferative effects of dinitramine (DN) on immature murine testicular cell lines (Leydig and Sertoli cells) mediated via endoplasmic reticulum (ER) stress-induced calcium dysregulation in the cytosol and mitochondria. The results demonstrated that the viability and proliferation of DN-treated TM3 and TM4 cells decreased significantly, even in the spheroid state. DN induced the apoptosis of TM3 and TM4 cells and decreased the expression of genes related to cell cycle progression. Treatment with DN increased the cytosolic and intramitochondrial levels of calcium by activating ER stress signals. DN activated the Erk/P38/Jnk Mapk pathway and inactivated the Pi3k/Akt pathway in murine testicular cells. Co-treatment with 2-aminoethoxydiphenyl borate (2-APB) mitigated DN-induced calcium upregulation in both testicular cell lines. Although 2-APB did not antagonize the anti-proliferative effect of DN in TM3 cells, treatment with 2-APB and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid restored the proliferation of DN-treated TM4 cells.

除草剂的危害性众所周知。然而，它们对生殖系统的影响尚不清楚。在这项研究中，我们证明了二硝胺（DN）对内质网（ER）应激诱导的细胞质和线粒体钙失调介导的未成熟鼠睾丸细胞系（Leydig和Sertoli细胞）的抗增殖作用。结果表明，即使在球状状态下，DN处理的TM3和TM4细胞的活力和增殖也显着降低。DN诱导TM3和TM4细胞凋亡，并降低与细胞周期进程相关的基因表达。DN处理可通过激活ER应激信号来提高钙的胞质和线粒体内钙水平。DN激活了小鼠睾丸细胞中的Erk / P38 / Jnk Mapk途径，并灭活了Pi3k / Akt途径。与2-氨基乙氧基二苯硼酸盐（2-APB）共同处理可缓解DN诱导的两种睾丸细胞系中的钙上调。尽管2-APB不能拮抗DN在TM3细胞中的抗增殖作用，但是使用2-APB和1,2-双（2-氨基苯氧基）乙烷-N，N，N'，N'-四乙酸可以恢复DN的抗增殖作用。 DN处理的TM4细胞的增殖。