Transcriptomic and network toxicology approaches reveal potential mechanisms of DEHP induced intrahepatic cholestasis during pregnancy.

The objective of this study was to investigate the hepatotoxic effects and molecular mechanisms underlying di(2-ethylhexyl) phthalate (DEHP)-induced intrahepatic cholestasis of pregnancy (ICP) through a network toxicology approach. Utilizing liver transcriptomics in conjunction with the GeneCards, DisGeNET, and OMIM databases, we identified 151 potential targets associated with DEHP-induced ICP. Subsequent analyses employing STRING and cytoscape software revealed five core targets: EGFR, STAT3, JUN, FOS, and HSP90AA1. Functional enrichment analysis via gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways indicated significant involvement in cholesterol synthesis, bile salt secretion, and the MAPK signaling pathway. Molecular docking studies conducted using AutoDock demonstrated strong binding affinities between DEHP and these core targets. In conclusion, this study offers novel insights into the molecular mechanisms of DEHP-induced hepatotoxicity during pregnancy while providing a systematic framework for assessing risks associated with DEHP exposure; thus contributing to the prevention and treatment of ICP.