Neurotoxicity and Mechanism in Zebrafish Embryo Induced by Tetrabromobisphenol A bis (2-Hydroxyethyl) Ether (TBBPA-DHEE) Exposure

Abstract

Tetrabromobisphenol A bis (2-hydroxyethyl) ether (TBBPA-DHEE), a derivative of TBBPA, has been frequently detected in the environment. In this study, the median lethal concentration (LC50) of TBBPA-DHEE at 96 h post-fertilization (hpf) was 1.573 mg/L. Based on the reported environmental concentrations, we investigated the effects of TBBPA-DHEE on the nervous system of zebrafish embryos following exposure to varying concentrations (0, 20, 100, and 500 μg/L) for 4 to 144 hpf. Our results indicated that exposure to 100 μg/L at 144 hpf led to behavioral abnormalities in zebrafish. Furthermore, exposure to TBBPA-DHEE inhibited the development of the central nervous system and motor neurons in zebrafish. Real-time polymerase chain reaction (PCR) analysis revealed that exposure to TBBPA-DHEE significantly downregulated the expression levels of neurodevelopmental genes (shha, syn2a, elavl3, gfap, and gap43). Additionally, TBBPA-DHEE increased oxidative stress in zebrafish. Transcriptomic analysis demonstrated that exposure to TBBPA-DHEE affected the signaling pathways involved in neurodevelopment. Overall, this study demonstrated that TBBPA-DHEE may disrupt the early development of the nervous system, leading to abnormal motor behavior in zebrafish larvae, and provided novel insights into the potential mechanisms of TBBPA-DHEE neurotoxicity.