Pendimethalin induces apoptosis in testicular cells via hampering ER-mitochondrial function and autophagy. (1st June 2021)

• Record Type: Journal Article
• Authors: Ham, Jiyeon; Lim, Whasun; Song, Gwonhwa
• Is Part Of: Environmental pollution. Volume 278(2021)
• Publication Date: 2021-06-01
• Subjects: Pendimethalin -- Herbicides -- ER stress -- Autophagy -- Inositol 1, 4, 5-triphosphate receptors; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.116835
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 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. Graphical abstract: Possible mechanisms of action of pendimethalin (PDM) in mouse Leydig and Sertoli cells. Image 1 Highlights: Pendimethalin inhibits cell growth and proliferation in mouse Leydig and Sertoli cells. Pendimethalin induces ROS production and ER stress in mouse testicular cells. Pendimethalin increases permeabilization of mitochondrial membrane potential. Pendimethalin induces cell-cycle arrest and apoptosis in mouse testicular cells. Pendimethalin may be harmful to the survival of testis cells, their function, and fertility. Abstract : Pendimethalin might be harmful to male testicular cells by suppressing the cell cycle and stimulating ER stress and mitochondrial dysfunction.