Dysregulated Fas/Fas ligand expression in endometrial stromal cells and mononuclear cells in endometriosis

Apoptosis plays a paramount role in endometriosis pathogenesis. This process may be disrupted in endometrial stromal cells (ESCs) of women with endometriosis, causing them to continue developing in ectopic locations. This study investigates the role of apoptosis in endometriosis by comparing the protein expression of Fas (CD95) and Fas ligand (FasL) in ESCs of women with endometriosis to that of healthy controls. Additionally, it examines the gene expression levels of Fas and FasL in peritoneal fluid mononuclear cells (PFMCs) and peripheral blood mononuclear cells (PBMCs) from both groups. Lastly, it assesses the levels of soluble FasL (sFasL) released by ESCs and PFMCs. ESCs were isolated from ectopic (n = 11) and eutopic samples (n = 17) of endometriosis patients and control (n = 10), alongside peritoneal fluid and blood samples from 10 patients and 10 controls. Using Western blot, Fas and FasL protein expression were assessed in ectopic endometrial stromal cells (EESCs), eutopic endometrial stromal cells (EuESCs), and control endometrial stromal cells (CESCs). Additionally, quantitative real-time PCR was used to evaluate Fas and FasL gene expression in PFMCs and PBMCs. Lastly, an enzyme-linked immunosorbent assay (ELISA) was conducted to assess the concentration of sFasL molecules in the supernatants of EESCs, EuESCs, CESCs, and PFMCs. Importantly, Fas protein levels in EESCs and EuESCs were lower than in CESCs (p < 0.01). Conversely, FasL protein levels were elevated in EESCs compared to both EuESCs and CESCs (p < 0.01 and p < 0.05, respectively). Additionally, patients with endometriosis exhibited higher Fas gene expression in PFMCs (p < 0.05) and lower expression in PBMCs (p < 0.01) compared to controls, along with reduced FasL expression in PFMCs (p < 0.01). Moreover, the concentration of sFasL molecules released from EESCs was significantly higher compared to EuESCs (p < 0.01) and CESCs (p < 0.05). All in all, our findings shed light on the understanding of the involvement of the Fas/FasL pathway in endometriosis pathogenesis.