Characterization of Metalaxyl-induced notochord toxicity based on biochemical and transcriptomics in zebrafish (Danio rerio) model

Metalaxyl is an acylanilide systemic fungicide that is widely applied and can readily enter ecosystems through leaching and soil runoff. This research utilized zebrafish as a model organism to thoroughly investigate the detrimental impacts of environmentally relevant levels of metalaxyl on the development of the notochord in zebrafish embryos and to elucidate the underlying molecular mechanisms through transcriptomics, pharmacological intervention and molecular biological detection. The preliminary results demonstrated that metalaxyl induced significant modifications in the developmental parameters of zebrafish embryos. This study has also assessed the long-term consequences of metalaxyl exposure during the embryonic development of zebrafish. This study have demonstrated that zebrafish exposed to metalaxyl exhibit a range of abnormalities, including defects in notochord vacuole biogenesis, somite segmentation disorders, anomalous notochord curvatures, craniofacial cartilage deformities, and irregular chordacentra mineralisation. Through transcriptomic and bioinformatics analysis, it was found that most of the genes exhibiting differential expression were linked to oxidative stress. Furthermore, the evidence indicated that oxidative stress was present, as demonstrated by increased malondialdehyde (MDA) production and a decrease in antioxidant enzyme activity (CAT, SOD, GSH). Interestingly, the developmental dysfunction induced by metalaxyl was partially rescued by chlorogenic acid. Overall, metalaxyl disrupts notochord and skeletal formation in zebrafish embryos by modulating oxidative stress mediated by reactive oxygen species.