Endocrine disrupting chemicals remodel inflammatory microenvironment of endometriosis via a GSTP1–NR3C1–SELE regulatory network: an integrative bioinformatics analysis

Abstract

Endocrine-disrupting chemicals (EDCs) are recognized environmental contributors to endometriosis, yet the mechanisms by which they remodel inflammatory signaling within the lesion microenvironment remain unclear. In this study, integrated bioinformatics and systems-toxicology approaches were applied to elucidate EDC-driven inflammatory regulatory networks in endometriosis. Targets of seven representative EDCs (BPA, BPAF, BPF, DEHP, TCDD, PCB-126, and DDT) were predicted and intersected with differentially expressed and inflammation-related genes in endometriosis. Protein–protein interaction network analysis combined with LASSO regression and the Boruta algorithm identified three core signature genes: GSTP1, NR3C1, and SELE. GSTP1 was significantly downregulated, whereas NR3C1 and SELE were upregulated in endometriosis. Correlation analysis revealed negative associations between GSTP1 and both NR3C1 and SELE, while NR3C1 and SELE showed a positive correlation. Moreover, this gene network was closely associated with immune cell infiltration, including activated CD4 ⁺ T cells, effector memory CD8 ⁺ T cells, and natural killer cells. These findings identify a GSTP1–NR3C1–SELE regulatory network linking EDC exposure to inflammatory microenvironment dysregulation in endometriosis, providing potential biomarkers and therapeutic targets.