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.