Tetrabromobisphenol A caused neurodevelopmental toxicity via disrupting thyroid hormones in zebrafish larvae

Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame retardants (BFRs), has resulted in worldwide environmental contamination. TBBPA has been reported as a thyroid endocrine disruptor and a potential neurotoxicant. However, the underlying mechanism is still not clear. In this study, zebrafish (Danio rerio) embryos (2 h post-fertilization, hpf) were exposed to different concentrations of TBBPA (50, 100, 200 and 400 μg/L) alone or in combination with 3,3',5-triiodo-l-thyronine (T3, 20 μg/L + TBBPA, 200 μg/L). The results confirmed that TBBPA could evoke thyroid disruption by observations of increased T4 contents and decreased T3 contents, accompanied by up-regulated tshβ, tg mRNA and down-regulated ttr and trβ mRNA levels in zebafish larvae. TBBPA-induced neurodevelopmental toxicity was also indicated by down-regulated transcription of genes related to central nervous system (CNS) development (e.g., α1-tubulin, mbp and shha), and decreased locomotor activity and average swimming speed. Our results further demonstrated that treatment with T3 could reverse or eliminate TBBPA-induced effects on thyroidal and neurodevelopmental parameters. Given the above, we hypothesize that the observed neurodevelopmental toxicity in the present study could be attributed to the thyroid hormone disruptions by TBBPA.