Evidence indicates that the initiation and progression of endometriosis are intimately tied to persistent psychological strain. The precise manner in which sustained stress contributes to metabolic alterations in women with endometriosis has not been elucidated. Our objective was to expose the mechanistic underpinnings of how sustained stress influences endometriosis evolution and, potentially, to formulate candidate biomarkers to gauge the effect of accelerated, persistent stress on endometriosis invasiveness. Ectopic tissue was excised surgically from ten affected patients, who were then separated into two categories through a psychological evaluation. A human mRNA gene expression microarray was used to assess differences in mRNA expression patterns between those under continuous stress and their counterparts. The reliability of the microarray results was further corroborated by metabolite profiling using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and quantitative reverse transcription polymerase chain reaction (RT–PCR). Microarray analysis of genes that were markedly overexpressed and differentially expressed between the ongoing stress and comparison groups revealed genes largely belonging to metabolic and immunological pathways, including immune response processes, inhibition of T lymphocyte proliferation, leucine breakdown, and L-cysteine processing (P < 0.05). LC-MS profiling demonstrated that the distinguishing metabolites chiefly involved arginine and proline processing, D-glutamine and D-glutamate processing, aspartate handling, glycine, serine metabolism, and tyrosine metabolism (P < 0.05). A mechanism may exist in which prolonged stress impairs immune defense in endometriosis via metabolic reconfiguration. Extended stress curtails the provision of energy substrates such as arginine and serine, suppresses T lymphocyte activation, and weakens antineoplastic immunity, thus facilitating the displacement and penetration of endometriotic tissue in chronically stressed patients.
