Low-level tetrabromobisphenol A (TBBPA) exposure disrupts early embryonic architecture: molecular impacts on dorsoventral patterning

Tetrabromobisphenol A (TBBPA), a widely used flame retardant in textiles and electronics, poses toxicological risks through both environmental and indoor exposures. Biomonitoring studies have detected significant TBBPA levels in prenatal environments, including cord blood, raising concerns about developmental impacts. Using zebrafish as a model, this study addresses critical gaps in understanding how developmental TBBPA exposures perturb regulatory pathways that govern dorsoventral patterning. Embryos were exposed at 0.75- or 6-h post-fertilization (hpf) and phenotyped at 24 hpf, with tissue uptake quantified by LC-MS. At 24 hpf, embryos exhibited concentration-dependent ventralization characterized by loss of dorsal structures. Whole-mount immunohistochemistry revealed concentration-dependent alterations in dorsoventral, cell adhesion, and germ layer markers, indicating disruptions in cell migration and germ layer integrity. At later stages, even nontoxic exposures led to craniofacial and hematopoietic defects, linking early molecular perturbations to downstream developmental abnormalities. Although the phenotypes strongly resembled BMP pathway overactivation, co-exposure with the BMP inhibitor dorsomorphin failed to rescue the defects, suggesting involvement of alternative mechanisms. Collectively, these findings demonstrate that TBBPA disrupts proteins critical for cell migration, fate specification, and germ layer formation at environmentally relevant concentrations, fundamentally altering embryonic physiology prior to organogenesis and inducing systemic changes in tissue development.