The Role Of Unfolded Protein Response in the Pathogenesis of Endometriosis: Contribution of Peritoneal Fluid

ABSTRACT Research Question Endoplasmic reticulum (ER) stress caused by the accumulation of the misfolded/unfolded proteins in the ER and induces the unfolded protein response (UPR). Peritoneal fluid (PF) plays an important role in the pathogenesis of endometriosis. In this study, the role of ER stress-associated UPR in endometriosis and the contribution of PF were investigated. Design Normal, eutopic and ectopic endometrium tissues were divided into menstrual cycle phases and endometrial stromal cells (ESCs) were treated with 10%-20% concentration of control peritoneal fluid (N-PF) and PF obtained from women with endometriosis (E-PF) for 10-30-60 min and 24-48 h. UPR signaling proteins were analyzed immunohistochemically and immunocytochemically. The data were compared statistically. Results p-IRE1 was increased in ectopic glandular and stromal cells in the early proliferative phase compared to normal and eutopic endometrium. p-PERK increased in ectopic glandular and stromal cells in the late proliferative phase compared to normal endometrium. ATF6 was increased in ectopic glandular epithelium compared to normal endometrium in the proliferative phases, versus eutopic endometrium in the late secretory phase. p-IRE1 and p-PERK were increased in high concentrations of E-PF treated ESCs for 10-30-60 min compared to control. In E-PFs treated ESCs, p-IRE1 was decreased at 24-48 h compared to 30 min. Conclusions In conclusion, UPR pathways are activated in endometriosis, and p-PERK and p-IRE1 increased as a result of exposure to high dose E-PF in stromal cells. Our findings provide a basis for further studies searching for a potential biomarker for the diagnosis of endometriosis.