Metabolomic and molecular analysis reveals multiple pathways of TBBPA-induced developmental toxicity in zebrafish embryos

Abstract

Tetrabromobisphenol A (TBBPA), a commonly utilized flame retardant, presents potential risks to both environmental and human health, with particular concern regarding its impact on embryonic development.This study employed zebrafish embryos as a model organism to investigate the comprehensive toxicological effects of TBBPA exposure, integrating metabolomics analysis with molecular and biochemical approaches. Embryos exposed to TBBPA concentrations ranging from 0.5 to 1.5 mg/L exhibited significant dose-dependent developmental abnormalities, including pericardial edema, yolk sac enlargement, and body axis curvature. At 96 h, we observed 50 % mortality at 1 mg/L. At 144 h of exposure to 0.1 mg/L TBBPA, automated behavioral analysis revealed significant changes in larval swimming patterns, characterized by reduced total distance moved, shortened active swimming time, impaired acceleration parameters, and abnormal spatial distribution. UHPLC-Q-TOF-MS-based metabolomics analysis revealed substantial perturbations in multiple biochemical pathways, particularly affecting neurotransmitter metabolism, energy homeostasis, and oxidative stress responses. TBBPA exposure significantly disrupted dopamine and serotonin metabolism, evidenced by altered enzyme expression and metabolite levels. Notable changes in oxidative stress markers, including GSH, MDA, and SOD, indicated significant cellular damage, while inflammatory responses showed dysregulation of both pro- and anti-inflammatory cytokines. Energy metabolism was comprehensively affected, with disruptions in glycolysis, TCA cycle, and amino acid metabolism pathways. The study identified key metabolic signatures of TBBPA toxicity and elucidated the interconnected mechanisms underlying its developmental impacts, providing valuable insights for environmental risk assessment and regulatory considerations. These findings emphasize the complex nature of TBBPA toxicity and highlight the need for careful evaluation of its environmental impact, particularly concerning early developmental exposure.