Cyclooxygenase-2 in Endometriosis

Abstract

Endometriosis (EMS) is the most common gynecological disease in women of reproductive age, and it is associated with chronic pelvic pain, dyspareunia and infertility. As a consequence of genetic, immune and environmental factors, endometriotic lesions have high cyclooxygenase (COX)-2 and COX-2-derived prostaglandin E 2 (PGE 2) biosynthesis compared with the normal endometrium. The transcription of the PTGS2 gene for COX-2 is associated with multiple intracellular signals, which converge to cause the activation of mitogen-activated protein kinases (MAPKs). COX-2 expression can be regulated by several factors, such as estrogen, hypoxia, proinflammatory cytokines, environmental pollutants, metabolites and metabolic enzymes, and platelets. High concentrations of COX-2 lead to high cell proliferation, a low level of apoptosis, high invasion, angiogenesis, EMS-related pain and infertility. COX-2-derived PGE 2 performs a crucial function in EMS development by binding to EP2 and EP4 receptors. These basic findings have contributed to COX-2-targeted treatment in EMS, including COX-2 inhibitors, hormone drugs and glycyrrhizin. In this review, we summarize the most recent basic research in detail and provide a short summary of COX-2-targeted treatment.

Molecules and Prostaglandins Related to Embryo Tolerance

“…COX2 and PGE2 are related to the pathogenesis of endometriosis. A high level of COX-2 due to various factors such as estrogens, hypoxia and environmental pollutants could suppress apoptosis and increase cell proliferation through PGE2 and its receptors EP2, and EP4 in endometriosis (143). In addition, experimental studies with intralesional injections of ASA, in rabbits with peritoneal endometriosis, eliminate endometriotic lesions (144).…”

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

“…Among the inflammatory mediators stimulated, IL-8 [a neutrophil chemotactic factor, also called C-X-C motif chemokine ligand 8 (CXCL8)], monocyte chemoattractant protein-1 [MCP-1, also called C-C motif chemokine ligand 2 (CCL2)] and cyclooxygenase-2 [COX-2, the inducible enzyme responsible for synthesis of prostaglandins (PGs)], are well-studied 17 . COX-2 upregulation mediated by nuclear factor kappa-B (NF-κB) leads to increased levels of PGs.…”

Untitled

“…Deep analysis of inflammation in rabbit kidney induced by ligation of the urethra shows that 45 that the contaminated organ surprisingly developed a massive ability to generate prostaglandins because of de novo synthesis of the fresh enzyme, but there was no proposal shown that the new enzyme was a different form 46,47 . In the next few years, the occurrence of two discrete forms of COX in brain tissue was established, which shows different sensitivities to indomethacin 48 .…”