Neurotoxic effects of 4-hydroxy-4'-isopropoxydiphenylsulfone exposure on zebrafish embryos

The central nervous system (CNS) is particularly vulnerable to endocrine-disrupting chemicals, especially bisphenol analogues. Bisphenol A (BPA), a widely studied compound, has been associated with various neurological disorders, leading to restrictions on its use and the subsequent adoption of alternative chemicals such as 4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP). However, concerns regarding the potential neurotoxicity of BPSIP have emerged. To evaluate the effects of BPSIP on neural development, zebrafish were exposed to a gradient of concentrations (0.05 mg/L, 0.5 mg/L, 5 mg/L) for 96 h post fertilization. Our results demonstrated that BPSIP exposure induced dose-dependent neurobehavioral abnormalities, including hypoactivity and reduced swimming distance. Furthermore, early-life exposure to BPSIP resulted in impaired brain morphology and increased neurocyte apoptosis. Transcriptomic analysis revealed that BPSIP exposure significantly disrupted neural development and function, particularly through modulations of the stress response and neurotransmitter-related pathways. Metabolomic profiling further confirmed these findings, showing significant alterations in dopaminergic and serotonergic neurotransmitter pathways in the BPSIP-treated larvae. Additionally, quantitative real-time PCR analysis of gene expression along these pathways corroborated the RNA-seq data. Our study findings provided compelling evidence that BPSIP exposure during early zebrafish development induced neurodevelopmental deficits through mechanisms such as apoptosis, energy metabolic dysfunction, and neurotransmitter disruption, even at environmentally relevant concentrations. These findings offer critical insights into the neurotoxic potential of emerging bisphenol analogues and underscore the need for further investigation into their impact on neural health.