The potential mechanisms of TBBPA bis(2-hydroxyethyl) ether induced developmental neurotoxicity in juvenile zebrafish (Danio rerio)

TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE), one of the main derivatives of TBBPA, has been widely detected in environmental samples and been discovered to be potential neurotoxic. In this study, the juvenile zebrafish were selected as the research subject to explore the neurotoxicity and its mechanism of low-dose TBBPA-DHEE exposure, and to reveal the neurotoxicity susceptibility in different sexes. Behavioral studies revealed that TBBPA-DHEE could significantly reduce the swimming velocity, maximum acceleration and cu-mulative duration of high-speed mobility, significantly increasing the cumulative duration of low-speed mobility and average social distance. It significantly reduced the contents of ATP, glutamate and Ca2+ in the whole brain. The histopathological study demonstrated that TBBPA-DHEE could cause brain tissue damage in female and male juvenile zebrafish. The comprehensive data analysis indicated that female zebrafish were more susceptible to TBBPA-DHEE exposure than male zebrafish. Transcriptomic analysis showed that TBBPA-DHEE could signifi-cantly affect the expressions of behavioral and development-related genes. Furthermore, female and male ju -venile zebrafish have different molecular mechanisms of neurotoxicity. For female juvenile zebrafish, the potential mechanism of neurotoxicity could be that it interfered with the feedback regulation of nerves by affecting the related genes expressions in the signaling pathways such as Ca2+ signaling, Wnt signaling and synapses. For male juvenile zebrafish, the potential mechanism of neurotoxicity may be through affecting the expression of related genes in hormones and neuro-related genes. This research could reveal the potential neurotoxicity of TBBPA-DHEE to aquatic organisms, which will be helpful to reveal the health effects of the emerging environmental pollutants.

Automated summary

This study investigated the neurotoxicity and mechanism of low-dose TBBPA-DHEE exposure in juvenile zebrafish and identified differences in neurotoxicity susceptibility between sexes. The research found that TBBPA-DHEE significantly affected swimming behavior and brain biochemistry in zebrafish, causing brain tissue damage. The study also revealed that female zebrafish are more susceptible to TBBPA-DHEE exposure than males, and different molecular mechanisms of neurotoxicity exist between the sexes. These findings contribute to the understanding of the potential health effects of emerging environmental pollutants.