2,6-Dibromophenol inhibits fin regeneration in zebrafish larvae via Wnt-mediated immune cell recruitment

2,6-Dibromophenol (2,6-DBP), a typical brominated phenolic disinfection byproduct, is frequently detected in drinking water after disinfection. However, its effect on tissue regeneration has not been previously reported. In this study, using the zebrafish larvae caudal fin regeneration model, we investigated the impact of acute exposure to a high concentration of 2,6-DBP on fin regeneration. The findings revealed that exposure to 2,6-DBP impaired tailfin regeneration and reduced locomotor activity, accompanied by increased apoptosis and decreased cell proliferation in the regenerating tailfin region. Furthermore, 2,6-DBP hindered the recruitment of neutrophils and macrophages, suppressed Wnt signaling pathway activity, and downregulated the expression of immune-related genes and genes associated with the Wnt signaling pathway. Pharmacological activation with either LPS (Lipopolysaccharide) or BML-284 partially rescued the regenerative defects in the tailfin region. Notably, pharmacological activation with BML-284 not only enhanced the recruitment of neutrophils and macrophages to the injury site but also restored the expression of immune-related genes. Collectively, these results indicate that 2,6-DBP inhibits fin regeneration in zebrafish larvae via Wnt-mediated recruitment of immune cells. This study provides novel insights into the ecological risks posed by disinfection byproducts to tissue repair and population recovery in aquatic vertebrates.