Pendimethalin (PDM) is a dinitroaniline crop pesticide that is extensively utilized worldwide. However, the reproductive toxicity and cellular mechanisms of PDM have not been identified. Therefore, we elucidated the adverse effects of PDM on the reproductive system using mouse testicular Leydig and Sertoli cells (TM3 and TM4 cells, respectively). Our results demonstrated that PDM suppressed the viability and proliferation of TM3 and TM4 cells. Additionally, PDM induced cytosolic calcium upregulation and permeabilization of mitochondrial membrane potential in both TM3 and TM4 cells. We also verified that PDM activates the endoplasmic reticulum (ER) stress pathway and autophagy. Furthermore, we confirmed that activation of ER stress and autophagy were blocked by 2-aminoethoxydiphenyl borate (2-APB) treatment. Finally, we confirmed PDM-induced cell cycle arrest and apoptosis in TM3 and TM4 cells. Thus, we first demonstrated that PDM impedes the survival of testis cells, and further, their function.

戊二甲灵（PDM）是一种二硝基苯胺类农作物农药，在世界范围内得到广泛利用。但是，尚未确定PDM的生殖毒性和细胞机制。因此，我们阐明了PDM对使用小鼠睾丸Leydig和Sertoli细胞（分别为TM3和TM4细胞）的生殖系统的不利影响。我们的结果表明，PDM抑制了TM3和TM4细胞的活力和增殖。此外，PDM诱导TM3和TM4细胞中的胞质钙上调和线粒体膜电位的通透性。我们还验证了PDM激活内质网（ER）应激途径和自噬。此外，我们证实，ER应激的激活和自噬被2-氨基乙氧基二苯基硼酸酯（2-APB）处理所阻断。最后，我们证实了PDM诱导的TM3和TM4细胞的细胞周期停滞和凋亡。因此，我们首先证明了PDM会阻碍睾丸细胞的存活，进而阻碍它们的功能。