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Objective: To investigate the level of expression of prostaglandin receptivity and uptake factors in eutopic and ectopic endometrium of women with endometriosis., Design: Prospective study., Setting: Human reproduction research laboratory., Patients: Seventy-eight patients with endometriosis and thirty healthy control subjects., Intervention(s): Endometrial and endometriotic tissue samples were obtained during laparoscopic surgery., Main Outcome Measure(s): Real-time polymerase chain reaction assay of mRNA encoding prostaglandin E2 receptors (EP1, EP2, EP3, and EP4), prostaglandin F2α receptor (FP), prostaglandin transporter (PGT), and multidrug resistance-associated protein 4 (MRP4); immunohistochemical localization of expressed proteins., Results: Marked increases in receptors EP3, EP4, and FP and transporters PGT and MRP4 in ectopic endometrial tissue were noted, without noticeable change associated with disease stage. An increase in EP3 expression and decreases in FP and PGT were observed in the eutopic endometrium of endometriosis patients in conjunction with the phases of the menstrual cycle., Conclusion(s): This study is the first to demonstrate a possible relationship between endometriosis and enhanced prostaglandin activity. In view of the wide range of prostaglandin functions, increasing cell receptivity and facilitating uptake in endometrial tissue could contribute to the initial steps of overgrowth and have an important role to play in the pathogenesis and symptoms of this disease.

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

Objective: To investigate prostaglandin (PG) biosynthesis and catabolism pathways in eutopic and ectopic endometrium of women with endometriosis., Design: Retrospective study., Setting: Human reproduction research laboratory., Patient(s): Forty-five women with endometriosis and 29 normal controls., Intervention(s): Endometrial and endometriotic tissue samples were obtained during laparoscopic surgery., Main Outcome Measure(s): Cyclo-oxygenases (Coxs 1 and 2), PGE2 synthases (microsomal [m] PGES 1 and 2 and cytosolic [c] PGES), PGF2α synthases (aldoketoreductase [AKR]-1C3 and AKR-1B1), and the PG catabolic enzyme 15-hydroxyprostaglandin dehydrogenase messenger RNA expression by quantitative real-time polymerase chain reaction and protein localization by immunohistochemistry., Result(s): This study showed a marked increase in the key PG biosynthesis enzymes Cox-2, mPGES-1, mPGES-2, cPGES, and AKR-1C3 in ectopic endometrial tissue of women with endometriosis, particularly in the earliest and most active stages of the disease, without a noticeable change in the expression of the PG catabolic enzyme 15-hydroxyprostaglandin dehydrogenase. Meanwhile, the significant increase in rate-limiting Cox-2 expression upstream was correlated downstream by a significant stage- and cycle phase-dependent decrease in the terminal specific synthase mPGES-2, thereby revealing the presence of counter-regulatory mechanisms, which operate in the eutopic endometrium of women with endometrium but seem to be lacking in the ectopic implantation sites., Conclusion(s): This study reveals for the first time multiple defects in PG biosynthesis pathways, which differ between eutopic intrauterine and ectopic endometrial tissues and may, owing to the wide spectrum of PG properties, contribute to the initial steps of endometrial tissue growth and development and have an important role to play in the pathogenesis and symptoms of this disease., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)