Flurochloridone induces Sertoli cell apoptosis through ROS-dependent mitochondrial pathway

Weiqi Sun; Zhijing Ni; Rui Li; Xiuli Chang; Weihua Li; Mingjun Yang; Zhijun Zhou

doi:10.1016/j.ecoenv.2021.112183

Flurochloridone induces Sertoli cell apoptosis through ROS-dependent mitochondrial pathway

Ecotoxicol Environ Saf. 2021 Mar 31:216:112183. doi: 10.1016/j.ecoenv.2021.112183. Online ahead of print.

Authors

Weiqi Sun¹, Zhijing Ni¹, Rui Li², Xiuli Chang¹, Weihua Li³, Mingjun Yang⁴, Zhijun Zhou⁵

Affiliations

¹ School of Public Health/ MOE Key Laboratory for Public Health Safety/ Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China.
² Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
³ Key Laboratory of Reproduction Regulation of National Health Commission (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China.
⁴ Key Laboratory of Reproduction Regulation of National Health Commission (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China. Electronic address: mingjun0707@163.com.
⁵ School of Public Health/ MOE Key Laboratory for Public Health Safety/ Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China. Electronic address: zjzhou@fudan.edu.cn.

PMID: 33812209
DOI: 10.1016/j.ecoenv.2021.112183

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: Apoptosis; Flurochloridone; Mitochondria dysfunction; Oxidative stress; Sertoli cell.