Bisphenols induce cardiotoxicity in zebrafish embryos: Role of the thyroid hormone receptor pathway

Bisphenols are frequently found in the environment and have been of emerging concern because of their adverse effects on aquatic animals and humans. In this study, we demonstrated that bisphenol A, S, and F (BPA, BPS, BPF) at environmental concentrations induced cardiotoxicity in zebrafish embryos. BPA decreased heart rate at 96 hpf (hours post fertilization) and increased the distance between the sinus venosus (SV) and bulbus arteriosus (BA), in zebrafish. BPF promoted heart pumping and stroke volume, shortened the SV-BAdistance, and increased body weight. Furthermore, we found that BPA increased the expression of the dio3b, thrβ, and myh7 genes but decreased the transcription of dio2. In contrast, BPF downregulated the expression of myh7 but upregulated that of thrβ. Molecular docking results showed that both BPA and BPF are predicted to bind tightly to the active pockets of zebrafish THRβ with affinities of -4.7 and -4.77 kcal/mol, respectively. However, BPS did not significantly affect dio3b, thrβ, and myh7 transcription and had a higher affinity for zebrafish THRβ (-2.13 kcal/mol). These findings suggest that although BPA, BPS, and BPF have similar structures, they may induce cardiotoxicity through different molecular mechanisms involving thyroid hormone systems. This investigation provides novel insights into the potential mechanism of cardiotoxicity from the perspective of thyroid disruption and offer a cautionary role for the use of BPA substitution.