Multi-scale analysis reveals key targets mediating BPA-induced sensorineural hearing loss.

Area of Science:

• Toxicology
• Genetics
• Otolaryngology

Background:

• The toxic mechanism of bisphenol A (BPA) in causing sensorineural hearing loss (SNHL) is not fully understood.
• Investigating BPA's impact on SNHL is crucial for public health due to widespread exposure.

Purpose of the Study:

• To elucidate the toxicological mechanisms of BPA-induced SNHL.
• To identify genes and pathways involved in BPA's ototoxicity.

Main Methods:

• Utilized network toxicology and Mendelian randomization to analyze BPA toxicity and identify causal genes for SNHL.
• Performed molecular docking and dynamic simulations to validate ligand-protein binding.
• Screened 92 BPA target genes related to SNHL and enriched pathways.

Main Results:

• BPA is classified as a Class 4 toxicant, impacting the blood-brain barrier, mitochondrial potential, and estrogen receptor alpha.
• Identified 92 BPA target genes associated with SNHL, enriched in potassium ion channel processes and MAPK/PI3K-Akt pathways.
• Mendelian randomization identified MANBA, PDE6D, and vascular endothelial growth factor A as causal genes for SNHL with BPA exposure.

Conclusions:

• BPA induces SNHL through disruption of potassium channels and MAPK/PI3K-Akt signaling pathways.
• MANBA, PDE6D, and vascular endothelial growth factor A are key mediators in BPA-induced SNHL.
• Findings provide insights into the molecular basis of BPA ototoxicity and potential therapeutic targets.