Bifenthrin impairs the functions of Leydig and Sertoli cells in mice via mitochondrion-endoplasmic reticulum dysregulation. (November 2020)

• Record Type: Journal Article
• Authors: Ham, Jiyeon; You, Seungkwon; Lim, Whasun; Song, Gwonhwa
• Is Part Of: Environmental pollution. Volume 266:Part 3(2020)
• Publication Date: 2020-11
• Subjects: Bifenthrin -- Leydig and Sertoli cells -- Apoptosis -- MAPK/PI3K pathway -- Steroidogenesis -- Testis dysfunction; 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.2020.115174
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Bifenthrin (BF) is a synthetic insecticide that is widely used in fields, resulting in an increase in its exposure to animals. However, reports on the toxic effects of BF on mammalian species and the underlying mechanism are still lacking. Here, we elucidated the mechanism underlying the toxic effects of BF on mouse reproduction using cell lines of immature mouse Leydig (TM3) and Sertoli (TM4) cells, which are constituent cells of testes. Our results show that BF suppressed the proliferation and viability of TM3 and TM4 cells. Additionally, treatment with BF induced cell cycle arrest, apoptotic cell death, and DNA fragmentation. Mitochondrial dysfunction and disruption of calcium homeostasis were observed in BF-treated TM3 and TM4 cells. Further, bifenthrin modulated unfolded protein response and mitochondrion-associated membrane and mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) signaling pathways. The expression of the mRNAs related to cell cycle progression, steroidogenesis, and spermatogenesis was downregulated by BF, suggestive of testicular toxicity. Taken together, these results demonstrate the intracellular mechanism of action of BF to involve antiproliferative and apoptotic effects and testicular dysfunction in mouse testis. Graphical abstract: Illustration of the suggested mechanism underlying the effect of bifenthrin (BF) on mouse Leydig and Sertoli cells. Right arrows indicate activation, while blocked arrows indicate suppression. The italicized characters (gray) represent genes that are related to steroidogenesis and spermatogenesis. Image 1 Highlights: Bifenthrin induces cell cycle arrest and apoptosis of mouse Leydig and Sertoli cells. Bifenthrin disrupts mitochondrial dysfunction and calcium homeostasis in testis. Bifenthrin alters various transcription factors related to testicular function. Bifenthrin controls functional markers related to steroidogenesis and spermatogenesis. Bifenthrin induces ER stress and downregulates MAPK/PI3K pathway proteins, except Akt. Abstract : Bifenthrin induces testicular cell death by suppressing the cell cycle and stimulating ER stress and mitochondrial apoptosis-related proteins in mice.