Bisphenol A exacerbates chronic non-bacterial prostatitis by upregulating ITGAX and promoting M1 macrophage...

Chronic non-bacterial prostatitis (CNP) is a common urological disease, whereas the effects of bisphenol A (BPA) on CNP remain unclear. We systematically evaluated the associations between BPA and CNP by combining dietary exposure assessment, urinary BPA detection, and animal model validation, and performed integrated multi‑omics analyses to decipher the underlying molecular mechanisms. Dietary questionnaire data from 1256 individuals showed that BPA exposure was associated with increased CNP risk (OR = 1.46, 95% CI: 1.08-1.98), particularly among individuals with BMI < 24 kg/m². Consistently, a case-control study of 120 participants further revealed elevated urinary BPA levels in patients with CNP and positive correlations with inflammatory cytokines. Such epidemiological observations were further recapitulated in the BPA‑exposed CNP animal model. Multi-omic integration identified ITGAX as a hub gene with increased expression in CNP and predicted binding affinity for BPA. Within BPA‑aggravated CNP lesions, M1 macrophages constituted the expanded immune subpopulation, wherein ITGAX colocalized with M1 macrophages and contributes to M1 macrophage polarization. Single-cell transcriptomic analysis further revealed that Itgax⁺ macrophages exhibited an M1-like phenotype and enhanced inferred communication with CD8⁺Gzmk⁺ effector-memory T cells. Collectively, these results suggest that BPA exposure may exacerbate CNP through ITGAX-associated macrophage inflammation, highlighting a potential mechanism linking BPA exposure to prostatitis.