Triphenyltin chloride suppresses caudal fin regeneration in zebrafish by inhibiting Wnt signaling.

Anthropogenic organotin pollutants, particularly triphenyltin chloride (TPTC), threaten aquatic ecosystems. However, their impact on tissue regeneration-a critical survival mechanism-remains poorly understood. Therefore, we used zebrafish larvae as a model organism to assess the effect of TPTC on caudal fin regeneration. We found that exposure to TPTC significantly inhibited caudal fin regeneration and affected the behavior of zebrafish larvae. In addition, TPTC increased the number of apoptotic cells and decreased the population of proliferating cells in the regenerating caudal fin. This was accompanied by dysregulated immune cell recruitment, manifested as a decrease in neutrophil numbers and an increase in macrophage numbers. TPTC exposure resulted in the inhibited Wnt pathway activity and the downregulation of core gene (wnt3a, fzd7a, β-catenin, lef1) expression levels during caudal fin. Critically, pharmacological activation of Wnt signaling using BML-284 rescued both regenerative capacity (75.2-84.1 % recovery) and the associated locomotor deficits. Together with exclusion of other major pathways, These results establish TPTC as an inhibitor of Wnt-mediated regeneration and reveal a novel ecotoxicological mechanism: pollutant at sub-lethal concentration levels exposure compromises tissue regeneration. This finding has broad implications for vertebrate resilience in contaminated habitats. And The remarkable fidelity of zebrafish caudal fin regeneration, coupled with its experimental tractability for genetic and chemical screening, has established it as a premier model for deciphering the core principles of vertebrate tissue repair.