Developmental effects of fenpropathrin on zebrafish (Danio rerio) embryo-larvae: Toxic endpoints and potential mechanism

Fenpropathrin (FEN), a highly efficient and broad-spectrum synthetic pyrethroid insecticide. Although sufficient concern has been given to the negative impacts of FEN on non-target organisms, limited knowledge exists regarding the developmental effects of FEN. In this study, effects of FEN (0.45, 1.35, 4.05, and 12.15 μg/L) on various early life-stage endpoints of zebrafish were investigated from 3 to 144 h post-fertilization (hpf) in order to disclose the developmental effects and underlying mechanisms caused by FEN. The results indicate that exposure to FEN induced developmental toxicity in zebrafish, including decreased heart rate, reduced blood flow, shorter body length, smaller eye size, non-inflated swim bladder, and disrupted craniofacial chondrogenesis, which were possibly due to a significant decrease in the levels of thyroxine (T4), triiodothyronine (T3), insulin-like growth factor-1 (IGF-1), and growth hormone (GH), increase in lipid accumulation, and alteration in the contents of total cholesterol (T-CHO) and triglyceride (TG) in larvae exposed to FEN. Besides, FEN exposure also resulted in the inhibition of spontaneous movement of embryo at 24 hpf, a decline in touch evoke response (TER) at 72 hpf, and a reduction in free-swimming activity at 144 hpf, as well as the larval activity at 144 hpf during the dark-light transition stimulus. Mechanistic examinations have shown that FEN treatment inhibits the activities of AChE and elevates the ACh levels. In addition, FEN exposure increased ROS levels and altered the levels of malondialdehyde (MDA), and induced apoptosis as determined by acridine orange staining and elevated caspase-3 levels, suggesting that the involvement of oxidative stress and apoptosis in FEN-induced developmental toxicity of embryos. Transcriptome sequencing of larvae showed that FEN altered the expressions of multiple metabolic and nervous system pathways, including PPAR signaling pathway, lipid metabolism pathway, carbohydrate metabolism pathway, retinol metabolism pathway, and neuroactive ligand-receptor interaction pathway, demonstrating that FEN alters the normal development of zebrafish embryos, and multiple pathways mediating the FEN-induced developmental toxicity. Overall, these findings enhance our understanding of the developmental toxic effects of FEN and provide fundamental data for assessing the risk of FEN on non-target organisms.