Toxicogenomic responses to zearalenone in Caenorhabditis elegans reveal possible molecular mechanisms of reproductive toxicity

• Published in: Food and chemical toxicology Vol. 122; pp. 49 - 58
• Main Authors: Yang, Zhendong, Xue, Kathy S., Sun, Xiulan, Williams, Phillip L., Wang, Jia-Sheng, Tang, Lili
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2018
• Subjects: Animals; Animals, Genetically Modified; C. elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - biosynthesis; Caenorhabditis elegans Proteins - genetics; Collagen - biosynthesis; Cuticle collagen biosynthesis; Development; Dose-Response Relationship, Drug; Estrogens, Non-Steroidal - administration & dosage; Estrogens, Non-Steroidal - toxicity; Female; Gene Expression Profiling; Gene Expression Regulation - drug effects; Genes, Helminth; Ovum - cytology; Real-Time Polymerase Chain Reaction; Reproduction; Reproduction - drug effects; Teratogens - toxicity; Zearalenone; Zearalenone - administration & dosage; Zearalenone - toxicity; Development; Zearalenone; C. elegans; Reproduction; Cuticle collagen biosynthesis
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2018.09.040

In this study, the possible molecular mechanisms of zearalenone (ZEA)-induced reproductive and developmental toxic effects in Caenorhabditis elegans (C. elegans) were investigated. Differential gene expression profiles were identified, and 171, 245, and 3149 genes were down- or up-regulated (>2.0 fold) in 10, 20, and 40 μg/ml ZEA treated groups, respectively, as compared to untreated controls. Pathway specific mapping showed that the major differentially expressed genes were collagen synthetic pathways regulating genes, col-121 and dpy-17. Real-time PCR reconfirmation of key genes, related to cuticle collagen synthetic pathway, found dramatic changes in the expression of the genes dpy-31, sqt-3, col-121, and dpy-17 following exposure to ZEA (40 μg/ml), which indicated the significance of these genes in ZEA-induced toxicity. Cuticle collagen plays many key roles in the development and reproduction of C. elegans. The hypersensitive responses in transgenic and mutant worms also confirmed the roles of these genes in lethality and reproductive response to ZEA exposure, which indicates that ZEA blocked the normal collagen processing and cuticle formation. Taken together, our results demonstrate that disruption of the collagen biosynthetic pathway might be a key mechanism in ZEA-induced reproductive and developmental toxic effects in C. elegans. •ZEA treatment for up to 40 μg/mL resulted in significant increase in generation time and decrease in egg production.•Up to 3149 genes were differentially expressed at 40 μg/mL ZEA, top results were involved in development and reproduction.•ZEA significantly altered gene expression of collagen synthetic pathway genes for up to 20 folds.•Disruption of collagen biosynthetic pathway may potentially be a key mechanism of ZEA toxicity in C. elegans.