Fatty Acid Binding Protein 4 Overexpression Contributes to Endometriosis via Mitochondria Dysfunction

Background: Endometriosis is a complex, multifactorial disease characterized by the growth of endometrial-derived cells outside the uterus. Abnormal proliferation of ectopic lesions and chronic inflammation contribute to the onset and progression of the condition. This study aimed to identify dysregulated genes involved in the pathogenesis of endometriosis. Methods: We performed differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) using gene expression datasets (GSE11691 and GSE23339) from the Gene Expression Omnibus (GEO). We then analyzed significant differentially expressed genes (DEGs) using Gene Set Enrichment Analysis (GSEA) to predict their functional roles. The expression of key DEGs was validated by immunohistochemistry (IHC) in ectopic and eutopic endometrial tissues from 14 patients with endometriosis. Primary endometrial cells were isolated from normal endometrial tissue. A candidate gene was overexpressed in these cells, and its effect on cellular metabolism was assessed by measurement of the oxygen consumption rate (OCR). Results: Our data identified 48 key dysregulated genes associated with endometriosis. These genes showed functional enrichment in processes such as complement activation and cell adhesion, both of which are implicated in disease pathogenesis. Notably, fatty acid binding protein 4 (FABP4), linked to mitochondrial dysfunction in endometrial stromal cells (ESCs), was one of the most significantly upregulated genes in ectopic endometrium. Overexpression of FABP4 enhanced cell growth and increased the OCR in primary endometrial cells. Conclusions: This study elucidates the functional role of FABP4 dysregulation in endometriosis and identifies it as a potential therapeutic target.