[Frontiers in Bioscience E4, 23-40, January 1, 2012]

Peritoneal endometriosis is an inflammatory disease

Jean-Christophe Lousse, Anne Van Langendonckt, Sylvie Defrere, Reinaldo Gonzalez Ramos, Sebastien Colette, Jacques Donnez

Universite Catholique de Louvain, Institut de Recherche Experimentale et Clinique (IREC), Department of Gynecology, 1200 Brussels, Belgium

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Peritoneal fluid and environment in peritoneal endometriosis
2.2. Oxidative stress and peritoneal endometriosis
3. Involvement of iron in the pathogenesis of peritoneal endometriosis
3.1. Iron overload in the peritoneal cavity of endometriosis patients
3.2. Origin of iron in the pelvic cavity
3.3. Iron metabolism in the pelvic cavity
3.4. Effect of iron overload on endometriosis development
3.5. Iron chelators as endometriosis treatment
4. Involvement of nuclear factor-kappa B in the pathogenesis of peritoneal endometriosis
4.1. The nuclear factor-kappa B signaling system
4.2. Nuclear factor-kappa B activation and endometriosis
4.3. Effect of nuclear factor-kappa B activation on endometriosis development
4.4. Nuclear factor-kappa B inhibitors as endometriosis treatment
5. Involvement of prostaglandins in the pathogenesis of peritoneal endometriosis
5.1. Eicosanoid biosynthesis
5.2. Prostaglandin receptors
5.3. Prostaglandin biosynthesis in endometriosis
5.4. Effect of prostaglandins on endometriosis development
5.5. Targeting prostaglandin biosynthesis as endometriosis treatment
6. Summary and perspectives
7. Acknowledgments
8. References

1. ABSTRACT

Peritoneal endometriosis is a chronic inflammatory disease characterized by increased numbers of peritoneal macrophages and their secreted products. Inflammation plays a major role in pain and infertility associated with endometriosis, but is also extensively involved in the molecular processes that lead to peritoneal lesion development. Peritoneal oxidative stress is currently thought to be a major constituent of the endometriosis-associated inflammatory response. Excessive production of reactive oxygen species, secondary to peritoneal influx of pro-oxidants such as heme and iron during retrograde menstruation, may induce cellular damage and increased proinflammatory gene expression through nuclear factor-kappa B activation. In particular, prostaglandin biosynthetic enzyme expression is regulated by this transcriptional factor, and increased peritoneal prostaglandin concentrations have been demonstrated in endometriosis. In the light of available data collected from patient biopsies, as well as in vitro and in vivo studies, the respective involvement and potential molecular interactions of iron, nuclear factor-kappa B and prostaglandins in the pathogenesis of endometriosis are explored and discussed. The key role of peritoneal macrophages is emphasized and potential therapeutic targets are examined.