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.

在这项研究中，研究了玉米赤霉烯酮（ZEA）引起秀丽隐杆线虫（C. elegans）生殖和发育毒性作用的可能分子机制。与未处理的对照组相比，分别在10、20和40μg/ ml的ZEA处理组中鉴定出差异基因表达谱，并且分别将171、245和3149基因下调或上调（> 2.0倍）。途径特异性作图表明，主要的差异表达基因是调节基因，col-121和dpy-17的胶原蛋白合成途径。与表皮胶原合成途径相关的关键基因的实时PCR重新确认发现dpy-31，sqt-3基因的表达发生了巨大变化，col-121和dpy-17暴露于ZEA（40μg/ ml）后，表明这些基因在ZEA诱导的毒性中具有重要意义。角质层胶原在秀丽隐杆线虫的发育和繁殖中起许多关键作用。转基因和突变蠕虫中的超敏反应也证实了这些基因在对ZEA暴露的致死性和生殖反应中的作用，这表明ZEA阻止了正常的胶原蛋白加工和表皮形成。两者合计，我们的结果表明，胶原生物合成途径的破坏可能是秀丽隐杆线虫诱导的ZEA诱导的生殖和发育毒性作用的关键机制。