The neurotoxicity and mechanism of TBBPA-DHEE exposure in mature zebrafish (Danio rerio)

Abstract

Tetrabromobisphenol A-bis (2-hydroxyethyl) ether (TBBPA-DHEE) has been detected in various environmental media and organisms, and its ecological risks and health hazards have attracted great attention, but sufficient toxicological data have not proved the toxic effects of TBBPA-DHEE exposure on aquatic organism. In this study, the neurotoxicity and mechanism of zebrafish (3-month-old) exposed to TBBPA-DHEE (0.86 μg/L, 12.9 μg/L, 193.5 μg/L) were studied. Furthermore, the neurotoxicity susceptibility of different sexes of zebrafish was revealed. Behavioral studies revealed that TBBPA-DHEE exposure has significant differences in average speed, duration of mania, the distance between objects, and ATP content between male and female zebrafish. Slight damage in brain tissue of male zebrafish was found. The transcriptome analysis revealed that the molecular mechanism of neurotoxicity in mature female and male zebrafish is different. For mature female zebrafish, TBBPA-DHEE significantly affected the expression of genes related to behavior and development, and its mechanism may be that it can produce neurotoxicity by affecting related genes in the hormone, synapse, and Ca2+ signaling pathway. For mature male zebrafish, TBBPA-DHEE can significantly affect their behavior and expression of nerve-related genes. Results from the transcriptomic analysis suggests that the possible molecular mechanism may be through the inhibition of Ca2+ signal transmission and produce neurotoxicity by affecting the expression of related genes in neural synapses, Ca2+ signal, and MAPK signal in brain tissue of zebrafish. The results suggested that exposure to low-dose TBBPA-DHEE could induce neurotoxicity in zebrafish, and female and male zebrafish showed different toxic effects and molecular mechanisms.