Carcinogenesis, Teratogenesis & Mutagenesis

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Differential gene expression and related pathways of skeletal malformations induced by deoxynivalenol  in mice

LI Yan,ZHAO Yinghui,ZHUANG Dongming,LI Xiaoxia,YU Ailian*   

  1. School of Basic Medicine Sciences, Taishan Medical University, Tai’an 271000, Shandong, China
  • Received:2014-05-11 Revised:2014-01-06 Online:2015-01-31 Published:2015-01-31

Abstract:

OBJECTIVE: To screen the differential gene expression and related pathways of fetal skeletal malformations induced by deoxynivalenol(DON) in mice,and to explore the mechanism of deformities induced by DON at the molecular level. METHODS:30 pregnant mice were randomly divided into 3 experimental groups and 2 control groups,6 in each group. DON injection was performed from days 7 to 10 of pregnancy by intraperitoneal injection into pregnant mice. At GD 18,all mice were killed under isoflurane anesthesia,and vertebral bone tissue of fetuses were collected. Total RNA of vertebral bone tissues was extracted and cDNA was obtained by RT-PCR. Using whole genome microarray technology,the gene expression profiles and the pathways of the rat vertebral bone tissue were studied. Analysis of the function of differentially expressed genes was performed by using software of gene ontology. Screening signaling pathways of differentially expressed genes was done by DAVID database. The results were verified by fluorescence quantitative PCR(qPCR) technology. RESULTS:Microarray analysis showed that 282 genes,including 148 down-regulated and 134 up-regulated genes,were abnormally expressed in fetal vertebral bones after maternal DON exposure. 153 pathways were related to the differentially expressed genes. The relative quantitative results of qPCR were consistent with the results of gene chip test in Fbn1,Co19a2,Papss2, Pax1,Runx2 and Pthlh genes. CONCLUSION: There were differential gene expressions in deformed fetal skeleton between deoxynivalenol-treated rats and normal rats, involving multiple signaling pathways. The differentially expressed genes and signaling pathways may be related to the molecular mechanisms of deformities induced by DON.

Key words: deoxynivalenol, skeletal deformities, gene chip, differentially expressed genes, signaling pathways