Exposure to multi-walled carbon nanotubes causes suppression in octopamine signal associated with transgenerational toxicity induction in C. elegans

Multi-walled carbon nanotube (MWCNT), a kind of carbon-based nanomaterials, has been extensively utilized in a variety of fields. In Caenorhabditis elegans, MWCNT exposure can result in toxicity not only at parental gen-eration (P0-G) but also in the offspring. However, the underlying mechanisms remain still largely unknown. DAF-12, a transcriptional factor (TF), was previously found to be activated and involved in transgenerational toxicity control after MWCNT exposure. In this study, we observed that exposure to 0.1-10 mu g/L MWCNTs caused the significant decrease in expression of tbh-1 encoding a tyramine beta-hydroxylase with the function to govern the octopamine synthesis, suggesting the inhibition in octopamine signal. After exposure to 0.1 mu g/L MWCNT, the decrease in tbh-1 expression could be also detected in F1-G and F2-G. Moreover, in germline cells, the TF DAF-12 regulated transgenerational MWCNT toxicity by suppressing expression and function of TBH-1. Meanwhile, exposure to 0.1-10 mu g/L MWCNTs induced the increase in octr-1 expression and the decrease in ser-6 expression. After exposure to 0.1 mu g/L MWCNT, the increased octr-1 expression and the decreased ser-6 expression were further observed in F1-G and F2-G. Germline TBH-1 controlled transgenerational MWCNT toxicity by regulating the activity of octopamine receptors (SER-6 and OCTR-1) in offspring. Furthermore, in the offspring, SER-6 and OCTR-1 affected the induction of MWCNT toxicity by upregulating or downregulating the level of ELT-2, a GATA TF. Taken together, these findings suggested possible link between alteration in octopamine related signals and MWCNT toxicity induction in offspring in organisms.