Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways

• Authors: Robert N. Taylor, Wake Forest University; Maureen A. Kane, University of Maryland; Neil Sidell, Emory University
• Journal Title: Seminars in Reproductive Medicine
• Volume: Volume 33, Number 4
• Publisher: Georg Thieme Verlag | 2015-07-01, Pages 246-256
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1055/s-0035-1554920
• Subjects: Health Sciences, Obstetrics and Gynecology; Health Sciences, Pathology; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Obstetrics & Gynecology; Reproductive Biology; chemokine; cytokine; metaplasia; retinoic acid; retrograde menstruation; MATRIX-METALLOPROTEINASE EXPRESSION; COMMON VARIABLE IMMUNODEFICIENCY; MONOCYTE CHEMOTACTIC PROTEIN-1; ESTROGEN RECEPTOR-BETA; GAMMA PPAR-GAMMA; STROMAL CELLS; BINDING-PROTEIN; IN-VITRO; PERITONEAL-FLUID; PROGESTERONE RESISTANCE

Abstract

Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease.