Etoxazole induces testicular malfunction in mice by dysregulating mitochondrial function and calcium homeostasis

Jiyeon Ham, Seungkwon You, Whasun Lim, Gwonhwa Song

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    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.

    Original languageEnglish
    Article number114573
    JournalEnvironmental Pollution
    Volume263
    DOIs
    Publication statusPublished - 2020 Aug

    Bibliographical note

    Funding Information:
    This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT( MSIT ) South Korea (Grant number: 2018R1C1B6009048 ).

    Publisher Copyright:
    © 2020 Elsevier Ltd

    Keywords

    • Etoxazole
    • Male infertility
    • Mitochondrial dysfunction
    • Pesticide
    • Steroidogenesis
    • Testis

    ASJC Scopus subject areas

    • Toxicology
    • Pollution
    • Health, Toxicology and Mutagenesis

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