ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

Toxins (Basel). 2018 Jan 1;10(1):24. doi: 10.3390/toxins10010024.


Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress and the ATP/AMPK pathway in ZEA-induced cell-cycle arrest and cell apoptosis was explored by using the antioxidant NAC, ER stress inhibitor 4-PBA and the AMPK inhibitor dorsomorphin, respectively. The results revealed that ZEA inhibited the cell proliferation, influenced the distribution of the cell cycle and induced cell apoptosis through the ATP/AMPK pathway. The ATP/AMPK pathway was regulated by ER stress that was induced by ROS generation after exposure to ZEA. Taking these together, this study provided evidence that ROS regulated the process of ZEA-induced cell cycle arrest and cell apoptosis through ER stress and the ATP/AMPK signal ways.

Keywords: AMPK signaling; ER stress; ROS; Sertoli cells; Zearalenone; cell apoptosis; cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Male
  • Mice
  • Reactive Oxygen Species / metabolism
  • Sertoli Cells / drug effects*
  • Sertoli Cells / physiology
  • Signal Transduction / drug effects
  • Zearalenone / toxicity*


  • Reactive Oxygen Species
  • Zearalenone
  • Adenosine Triphosphate
  • AMP-Activated Protein Kinases