Exploring the mechanism of phthalate esters and polycyclic aromatic hydrocarbons on gestational metabolic disorders based on network toxicology and molecular docking

Phthalates (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants linked to metabolic disorders, yet their role in gestational hypertension, gestational diabetes mellitus (GDM), and gestational obesity remians unclear. This study employed network toxicology and molecular docking to investigate the potential mechanisms by which 21 PAEs and PAHs influence these gestational conditions. We first predicted pollutant target genes using TargetNet and SwissTargetPrediction and cross-referenced them with disease-related genes from established databases to identify overlapping targets. Protein–protein interaction (PPI) networks were then constructed using the STRING database, followed by GO/KEGG enrichment analyses to determine the biological functions and pathways of these targets. Finally, molecular docking was performed to validate the interactions between key pollutants and identified hub proteins. Our analysis identified 149, 214, and 149 overlapping targets for gestational hypertension, GDM, and gestational obesity, respectively. The PPI networks highlighted central hub genes, including TNF, CASP3, BCL2, and ESR1, which were significantly enriched in pathways crucial for metabolism and cellular response, such as MAPK, calcium signaling, and insulin resistance. Docking simulations revealed strong binding affinities of several PAHs—notably benzo(b)fluoranthene, benzo(k)fluoranthene, and benzo(ghi)perylene—to the hub proteins TNF (–8.5 kcal/mol), BCL2 (–9.4 kcal/mol), and CASP3 (–6.8 kcal/mol). These findings suggest that PAEs and PAHs may contribute to gestational metabolic disorders through potential interactions with key regulators of inflammation, apoptosis, and metabolism. This research underscores the need for further investigation into the impact of environmental pollutants on maternal health during pregnancy.