Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Pestic Biochem Physiol. 2021 Jan;171:104731. doi: 10.1016/j.pestbp.2020.104731. Epub 2020 Oct 16.
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.
作为一种有机氯农药，哒螨灵（PDB）已被用于各种植物，包括水果植物和其他作物。由于人们对接触农药的担忧不断增加，哒螨灵的有害影响，包括神经元疾病和生殖异常，已经确定。然而，导致哒螨灵对男性生殖系统影响的细胞内机制尚不清楚。因此，我们使用小鼠睾丸细胞研究了哒螨灵对男性生殖器官（特别是睾丸）的影响。我们证明哒螨灵抑制了小鼠睾丸间质细胞（TM3）和支持细胞（TM4）的细胞增殖。此外，哒螨灵通过线粒体功能障碍和内质网应激破坏钙稳态。此外，哒螨灵抑制了与细胞周期、类固醇生成和精子发生有关的基因转录表达，这些是 TM3 和 TM4 细胞的主要功能。此外，我们通过 Western blot 分析证实，哒螨灵通过调控与线粒体相关的膜和 Mapk/Pi3k 途径中的细胞内信号通路来发挥作用。最后，我们证实哒螨灵能有效地抑制 TM3 和 TM4 细胞的球体形成，模拟体内环境。总之，目前的结果表明，哒螨灵通过诱导线粒体功能障碍、内质网应激和钙失衡，引起睾丸毒性和男性生殖异常。
