Effects Of Zearalenone On The Prolife Ration Of Mouse Thymic Epithe Lial Cells And The Related Mechanisms

Zearalenone（Zearalenone,ZEA）is caused by Fusarium graminearum,Fusarium culmorum and f.equiseti and Fusarium a class of fungi which have estrogenic act ivity of non steroidal mycotoxins.Thymus is an important immune organ in the body.It plays an important role in the immune function of animals.The thymic epithelial cells can directly affect the differentiation,development and maturation of T lymphocytes.In this study,mouse thymic epithelial cell line 1（MTEC1）were regarded as our research object to investigate the effect of ZEA on the proliferation of MTEC1 and its mechanism,which can provide laboratory evidences for assessing the toxicity of ZEA.The cell morphology of electron microscope technique,cell viability detection technology,Edu cell proliferation assay,DAPI staining,flow cytometry,transcriptome sequencing（RNA-seq）,real-time changes,fluorescent quantitative technique,to investigate the expression of ZEA on MTEC1 cell proliferation,cell viability,cell cycle related genes change etc.The results were as follows:（1）High concentration（10²5μg/mL）ZEA can significantly change the morphology of MTEC1 cells,with the ZEA processing time becomes longer,the morphological changes of thymic epithelial cells,from the original"paving stone"state into a mess.Cell viability decreased and cell proliferation was significantly inhibited（P<0.05）,there was dose correlation,but the time dependence was not strong.（2）High dose（10⁵0μg/mL）ZEA can significantly inhibit the cell cycle of mouse thymic epithelial cells in G₂/M phase（P<0.01）,induce cell cycle arrest in G₂/M phase,and may be dose-dependent.（3）ZEA can induce the expression of mRNA in MTEC1 cells,the transcriptome sequencing of ZEA group has significant difference changes occurred in 4,188 genes（|logFC|≥1 and FDR≤0.05）.Among them,2,156 genes were up-regulated and 2,032genes were down regulated.Special cause Chemokine,JAK-STAT and other signaling pathways and significant changes in mitotic catastrophe mechanism related gene Jak2,Stat1,Irf9,Plk1,Cdc25b expression was significantly reduced;Gnai2,Trpc1,Shc2,Nras,Mapk3,Bub1,Bub1b,Ttk,Cenpe,Cdc20,CyclinB1 expression was significantly up-regulated.Conclusion:The toxic effect of ZEA on MTEC1 cells in low concentration had a tendency to promote the proliferation,and had a significant inhibitory effect at high concentration（P<0.05）,and the blockage was in the G₂/M phase（P<0.01）.The effect of ZEA on MTEC1 proliferation may be mediated by cell signaling pathways such as Chemokine and JAK-STAT,as well as mitotic catastrophe mechanisms.