Folpet induces mitochondrial dysfunction and ROS-mediated apoptosis in mouse Sertoli cells

Jiyeon Ham, Bo Hyun Yun, Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticlepeer-review

Abstract

Folpet is a phthalimide type of fungicide and has been used to control several crop diseases. Although it has adverse effects on the gastrointestinal tract, its mechanism and toxic effects on testis have not been demonstrated. In the present study, we elucidated the cytotoxic effect of folpet on the mouse Sertoli cell line, TM4. Our results revealed that folpet suppressed viability and proliferative capacity of TM4 cells and further inhibited 3D spheroid formation. Moreover, folpet impeded appropriate cell cycle progression and induced apoptotic cell death in TM4 cells. It disrupted the electrochemical gradient of mitochondria and calcium homeostasis in TM4 cells. Furthermore, endoplasmic reticulum stress-related proteins were activated in folpet-treated TM4 cells, and relative reactive oxygen species (ROS) production was also increased. N-acetylcysteine (NAC) treatment reinstated the folpet-induced ROS generation in TM4 cells. Additionally, NAC restored the proliferative capacity and reduced the apoptotic cells in folpet-treated TM4 cells. Collectively, we demonstrated that folpet causes ROS-mediated apoptotic cell death with mitochondrial dysfunction and calcium dysregulation in TM4 cells.

Original languageEnglish
Article number104903
JournalPesticide Biochemistry and Physiology
Volume177
DOIs
Publication statusPublished - 2021 Aug

Keywords

  • Folpet
  • Fungicides
  • Mitochondria
  • Oxidative stress
  • ROS
  • Sertoli cell

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Health, Toxicology and Mutagenesis

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