Etoxazole induces testicular malfunction in mice by dysregulating mitochondrial function and calcium homeostasis. (August 2020)

• Record Type: Journal Article
• Authors: Ham, Jiyeon; You, Seungkwon; Lim, Whasun; Song, Gwonhwa
• Is Part Of: Environmental pollution. Volume 263(2020)Supplement Part A
• Publication Date: 2020-08
• Subjects: Etoxazole -- Pesticide -- Testis -- Mitochondrial dysfunction -- Steroidogenesis -- Male infertility; 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.2020.114573
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Epidemiological relationships between pesticide use and male infertility have been suggested for a long time. Etoxazole (ETX), an oxazoline pesticide, has been extensively used for pest eradication. It is considered relatively safe and has low mammalian toxicity because it specifically inhibits chitin synthesis. However, ETX may have toxic effects on the reproductive system. In this study, we examined the effects of ETX on the reproductive system using mouse testis cell lines (TM3 for Leydig cells and TM4 for Sertoli cells) and C57BL/6 male mice. We confirmed that ETX has anti-proliferative effects on the TM3 and TM4 cell lines. Moreover, ETX induced mitochondrial dysfunction and hampers calcium homeostasis. Western blot analysis of MAPK and Akt signaling cascades was performed to demonstrate the mode of action of ETX at a molecular level. Moreover, ETX induced misregulation of genes related to testicular function. Upon oral administration of ETX in C57BL/6 male mice, testis weight was reduced and transcriptional expression related to testis function was altered. These results indicate that ETX induces testicular toxicity by inducing mitochondrial dysfunction and calcium imbalance and regulating gene expression. Graphical abstract: Schematic illustration of the cellular mode of action of ETX in mouse Leydig and Sertoli cells. ETX exerted anti-proliferative effects in mouse Leydig (TM3) and Sertoli (TM4) cells via the regulation of signal transduction related to MAPK and PI3k/Akt pathways, along with mitochondrial dysfunction and disruption of calcium homeostasis. Image 1 Highlights: Etoxazole causes mitochondrial dysfunction and calcium imbalance in testicular cells. Etoxazole induces mis-regulation of genes related to testicular function in testicular cells. Etoxazole alters transcriptional expression related to testis function in mice.