Flurochloridone induces Sertoli cell apoptosis through ROS-dependent mitochondrial pathway

Abstract

Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity which underlying mechanism is still largely unknown. The present study was conducted to determine the effects of FLC on Sertoli cell and explore its mechanism by using normal mouse Sertoli (TM4) cell line. Our data indicate that FLC suppressed proliferation of TM4 cells in a dose- and time-dependent manner. Further studies confirmed that FLC induced apoptosis in TM4 cells, accompanied by reactive oxygen species (ROS) accumulation, intracellular calcium increase, opening of mitochondrial permeability transition pore, depolarization of the mitochondrial membrane potential (MMP) and decrease of adenosine triphosphate (ATP) level. Meanwhile, changes of B-cell lymphoma-2 (Bcl-2) family proteins expression, release of cytochrome c and the activation of caspase-9 and caspase-3 were also confirmed. These results indicate that FLC induces TM4 cells apoptosis through the mitochondrial apoptotic pathway. In addition, pretreatment with ROS scavenger N-acetyl-L-cysteine (NAC), could significantly alleviate FLC-induced TM4 cells apoptosis and MMP depolarization. In conclusion, our results suggested that FLC induced TM4 cells apoptosis and it was regulated by mitochondrial dysfunction and oxidative stresses.

Keywords

• Flurochloridone
• Sertoli cell
• Apoptosis
• Oxidative stress
• Mitochondria dysfunction