As an organochloride pesticide, pyridaben (PDB) has been used on various plants, including fruiting plants and other crops. Because of emerging concerns regarding exposure to pesticides, the deleterious effects of PDB, including neuronal disease and reproductive abnormalities, have been determined. However, the intracellular mechanisms that contribute to the effects of PDB on the male reproductive system are still unknown. Therefore, we investigated the effects of PDB on the male reproductive organ, focusing on the testes using mouse testicular cells. We demonstrated that PDB suppressed cellular proliferation of mouse Leydig (TM3) and Sertoli (TM4) cells. Additionally, PDB disturbed calcium homeostasis via mitochondrial dysfunction and activation of endoplasmic reticulum stress. Furthermore, PDB inhibited transcriptional gene expression regarding the cell cycle, as well as steroidogenesis and spermatogenesis, which are the primary functions of TM3 and TM4 cells. Moreover, we verified via western blot analysis that PDB dysregulated the intracellular cell signaling pathways in mitochondrial-associated membranes and the Mapk/Pi3k pathway. Lastly, we confirmed that PDB efficiently suppressed the spheroid formation of TM3 and TM4 cells mimicking an in vivo environment. Collectively, the current results indicate that PDB induces testicular toxicity and male reproductive abnormalities by inducing mitochondrial dysfunction, endoplasmic reticulum stress and calcium imbalance.

中文翻译：

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Pyridaben 诱导线粒体功能障碍并导致潜在的男性生殖异常

作为一种有机氯化物杀虫剂，哒螨灵 (PDB) 已被用于各种植物，包括果树和其他作物。由于对接触杀虫剂的新担忧，PDB 的有害影响，包括神经元疾病和生殖异常，已被确定。然而，导致 PDB 对男性生殖系统影响的细胞内机制仍然未知。因此，我们研究了 PDB 对男性生殖器官的影响，重点是使用小鼠睾丸细胞的睾丸。我们证明 PDB 抑制了小鼠 Leydig (TM3) 和 Sertoli (TM4) 细胞的细胞增殖。此外，PDB 通过线粒体功能障碍和内质网应激的激活扰乱了钙稳态。此外，PDB 抑制有关细胞周期的转录基因表达，以及类固醇生成和精子生成，这是 TM3 和 TM4 细胞的主要功能。此外，我们通过蛋白质印迹分析证实 PDB 失调了线粒体相关膜中的细胞内细胞信号通路和 Mapk/Pi3k 通路。最后，我们证实 PDB 有效抑制了模拟体内环境的 TM3 和 TM4 细胞的球体形成。总的来说，目前的结果表明 PDB 通过诱导线粒体功能障碍、内质网应激和钙失衡来诱导睾丸毒性和男性生殖异常。我们通过蛋白质印迹分析证实 PDB 失调了线粒体相关膜中的细胞内细胞信号通路和 Mapk/Pi3k 通路。最后，我们证实 PDB 有效抑制了模拟体内环境的 TM3 和 TM4 细胞的球体形成。总的来说，目前的结果表明 PDB 通过诱导线粒体功能障碍、内质网应激和钙失衡来诱导睾丸毒性和男性生殖异常。我们通过蛋白质印迹分析证实 PDB 失调了线粒体相关膜中的细胞内细胞信号通路和 Mapk/Pi3k 通路。最后，我们证实 PDB 有效抑制了模拟体内环境的 TM3 和 TM4 细胞的球体形成。总的来说，目前的结果表明 PDB 通过诱导线粒体功能障碍、内质网应激和钙失衡来诱导睾丸毒性和男性生殖异常。