Biochemical toxicity and transcriptome aberration induced by dinotefuran in Bombyx mori

Dinotefuran is the third neonicotinoid pesticide and increasingly used in agricultural production, which has proved to cause adverse effects to non-target organisms. However, the toxicological effects of dinotefuran on non-target insects are still limited. Here, the toxic effects of dinotefuran on a lepidopteran model insect, Bombyx mori were investigated. Exposure to different doses of dinotefuran caused physiological disorders or death. The activities of cytochrome P450s, glutathione S-transferases, carboxylesterases, and UDP glycosy-transferases were induced in the fat body at the early stages after dinotefuran exposure. By contrast, the activity of glutathione S-transferase was only upregulated in the midgut. To overcome the insensitivity of the bioassays at the individual organism level, RNA sequencing was performed to measure mRNA differential expressions for silkworm larvae after dinotefuran exposure. Global transcriptional pattern showed that the physiological responses induced by dinotefuran toxicity involved in multiple cellular processes, including oxidative stress, detoxification enzymes, detoxification regulation, energy metabolism, and other fundamental physiological processes. The differential gene expression profile revealed that a variety of detoxification enzyme genes were significantly increased after dinotefuran exposure, which was consistent with detoxifying enzyme upregulation. Many metabolism progresses, such as carbon metabolism, glycolysis/gluconeogenesis and fatty acid biosynthesis, were partially repressed in the midgut or fat body. In addition, dinotefuran significantly activated MAPK/CREB, CncC/Keap1, IMD, and PI3K/Akt pathways. The links between physiological biochemical toxicity and comparative transcriptomic analysis facilitated a systematic understanding of integrated bio toxicity of dinotefuran. This study provides holistic insight into the ecological risk assessment of dinotefuran in organisms and pollution control.