Journal
TOXICOLOGY IN VITRO
Volume 54, Issue -, Pages 243-250Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2018.09.020
Keywords
Zearalenone (ZEN); Embryotoxicity; Embryonic stem cell (ESC); Murine embryonic stem cell test (mEST); Human embryonic stem cell test (hEST); Reactive oxygen species (ROS); Oxidative stress; Apoptosis
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Funding
- National Natural Science Foundation of China [81302462]
- Natural Science Foundation of Beijing Municipality [7142128]
- China Food Safety Talent Competency Development Initiative: CFSA 523 Program
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In this study, murine embryonic stem cell test (mEST) and human embryonic stem cell test (hEST) models were developed to evaluate the embryonic toxicity of Zearalenone (ZEN) according to the methods established in our laboratory. The embryotoxicity of ZEN was described by comparing the three functions calculated based on three endpoints, that is, 50% inhibitory proliferation concentration (IC50) of embryonic stem cells (ESCs) and 3T3 cells and 50% inhibition of cardiomyocyte differentiation (ID50) of ESCs determined in the EST model. Moreover, differentiation of human embryonic stem cell (hESC) was initiated by embryoid bodies (EBs) formation; EBs were exposed to different concentrations of ZEN for 24 h to detect cellular reactive oxygen species (ROS) generation, the mitochondrial transmembrane potential (MMP), apoptosis, cell cycle, and the related protein expression. Based on the results of the three endpoints and functions of ZEN in mEST and hEST, ZEN was evaluated to have strong embryonic toxicity both by two models. The increases in cellular ROS and loss of MMP were observed at 2 and 4 mu g/ml concentrations. Flow cytometry showed that ZEN induced cell cycle arrest and apoptosis. The upregulation of p53, caspase-9, caspase-3, and the ratio of Bax/Bcl-2 were observed at 2 and 4 mu g/ml concentrations. Collectively these results demonstrate that ZEN has strong embryonic toxicity and induces oxidative stress and apoptosis in differentiated human ESCs.
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