GYNECOLOGICAL ENDOCRINOLOGY 

Minerva Endocrinologica 2014 September;39(3):167-74

Copyright © 2014 EDIZIONI MINERVA MEDICA

language: English

Role of advanced glycation end-products in obesity-related ovarian dysfunction

Merhi Z. ¹, Mcgee E. A. ¹, Buyuk E. ² ✉

¹ Division of Reproductive, Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA; ² Division of Reproductive, Endocrinology and Infertility, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY, USA

Obesity affects ovarian function, one of the main regulators of female fertility. Tissue levels of the proinflammatory advanced glycation end-products (AGEs) and their receptors (RAGE) are elevated in obesity. AGEs are key contributors to perturbations in the ovarian microenvironment. On this basis, the present review focuses on clinical and experimental studies supporting the role of AGE-RAGE system as a contributor to obesity-related ovarian dysfunction. Particular emphasis has been given to changes in AGEs, RAGE and the anti-inflammatory soluble receptor (sRAGE) levels in obesity state and following dietary interventions (high-fat diet and weight loss). Ovarian sensitivity, in particular granulosa cell function and oocyte meiosis, to the pro-inflammatory AGE-RAGE system as well as the relationship of follicular fluid AGEs and sRAGE to in vitro fertilization outcome are also discussed. Overall, obesity, with its alterations in the AGE-RAGE system, can disrupt the ovarian microenvironment potentially compromising oocyte competence and fertility. This review underscores a critical need to uncover the mechanistic actions of AGE-RAGE system in obesity-related ovarian dysfunction. Clinical and basic studies focusing on elucidating the patterns of accumulation and role of the AGE-RAGE system in human ovarian follicles are key steps in understanding their contribution to the health of human oocytes and embryos.