Spirodiclofen exposure disturbs zebrafish swim bladder formation: Statistical analysis and molecular modeling insights.

Pesticides are major environmental pollutants, and the swim bladder is highly sensitive to chemical stressors. However, the effects of spirodiclofen on swim bladder and the underlying mechanisms remain poorly understood despite its widespread environmental detection. In this study, zebrafish embroys were exposed to spirodiclofen to evaluate its impacts on the swim bladder. At 120 hpf, complete failure of swim bladder inflation was observed in the 0.146 mg/L and 0.300 mg/L treatment groups. Swim bladder area decreased by 40.3% and 52.8% (p < 0.01), and locomotor activity was markedly impaired, with total distance reduced by 87.4% and 95.5%, respectively (p < 0.01). RT-qPCR analysis revealed downregulate genes in Hedgehog and Wnt signaling pathways, as well as key developmental markers of swim bladder formation. Spirodiclofen also disrupted the prolactin pathway and significantly reduce Na⁺/K⁺-ATPase activity (p < 0.05), suggesting impaired ion regulation during inflation. Integrative GGE biplot analysis, molecular docking, and molecular dynamics simulations identified Wnt5b, Atp1b2, and Elovl1a as potential toxicity targets. Environmental monitoring further revealed that the risk quotients (RQ)> 1 at most sampling sites, underscoring the ecological relevance of these findings. Overall, this study provides mechanistic evidence for spirodiclofen-induced swim bladder toxicity and supports ecological risk assessment and the design of safer alternatives.