Exploring the Molecular Mechanisms of Autism Induced by Early Childhood Exposure to Bisphenol A Based on Network Toxicology and Molecular Docking

Early childhood exposure to bisphenol A (BPA) is closely associated with autism spectrum disorder (ASD), though the precise molecular mechanisms remain unclear. To investigate this, we employed an integrated computational approach combining network toxicology, molecular docking, and molecular dynamics simulation. Potential targets of BPA and ASD-related genes were collected from multiple databases, identifying 57 overlapping targets. Protein–protein interaction network analysis highlighted 16 core targets among them. Gene Ontology and KEGG pathway enrichment analyses indicated these targets are primarily involved in synaptic transmission, GABAergic signaling, and neuroactive ligand–receptor interactions. Molecular docking demonstrated potential binding between BPA and several core targets, including estrogen receptor 1 (ESR1), gamma-aminobutyric acid type A receptor subunit beta-2 (GABRB2), and amyloid precursor protein (APP), with binding energies below −5 kcal/mol. The stability of the BPA-ESR1 complex was further supported through 100 ns molecular dynamics simulation. These results suggest that BPA may contribute to ASD by disrupting neuroendocrine pathways and synaptic function via interactions with key targets such as ESR1.