DEHP induces stress urinary incontinence by causing urethral sphincter dysfunction via inflammation and apoptosis: a mechanism study based on animal experiments, network toxicology, and molecular docking.

OBJECTIVE

Di (2-ethylhexyl) phthalate (DEHP), a pervasive environmental pollutant, poses significant health risks, yet its role in stress urinary incontinence (SUI) remains largely unexplored.

METHODS

This study integrated network toxicology, molecular docking, and animal experiments to investigate DEHP-induced SUI mechanisms.

RESULTS

Through cross-analysis of multiple public databases, we identified 95 potential targets linking DEHP exposure to SUI. GO and KEGG enrichment analyses revealed that these targets are primarily involved in immune-related pathways, including apoptosis, TNF signaling, NOD-like receptor signaling, and inflammatory mediator regulation of TRP channels. Using protein interaction network analysis, we further identified five core targets (NFKB1, CASP3, BCL2, TLR4, MMP9). Molecular docking confirmed strong binding affinities between DEHP and these proteins. In vivo experiments demonstrated that DEHP exposure induces urethral sphincter damage and degeneration in rats, thereby accelerating SUI progression.

CONCLUSION

This study elucidates the molecular mechanisms underlying DEHP-induced SUI and highlights network toxicology as a powerful approach for assessing health risks of environmental contaminants.