Advanced glycation end products and their relevance in female reproduction

Do advanced glycation end products (AGEs) and their receptors play a role in female reproduction?AGEs might contribute to the etiology of polycystic ovary syndrome (PCOS) and infertility.The endogenous AGEs are produced in the body by chemical reactions. Exogenous sources of AGEs are diet and smoking. AGEs have been proposed to be among the main intermediaries involved in several diseases, such as metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease, ovarian aging, inflammation, neurodegenerative disorders and PCOS.A systematic review was performed for all available basic science and clinical peer-reviewed articles published in PubMed from 1987 to date. Abstracts of annual meetings of the Endocrine Society and American Society for Reproductive Medicine were also reviewed.A total of 275 publications and scientific abstracts were identified from the initial search. Sixty-two papers and four published scientific abstracts were selected for full review. The main outcomes were the regulatory effects of AGEs on: (i) granulosa cells, adipocyte physiology, obesity and insulin resistance in women with PCOS and in polycystic ovary animal models and (ii) infertility and measures of ovarian reserve.There is an intricate relationship between the AGE-RAGE (receptor for AGEs) system and some aspects of PCOS, such as granulosa cell dysfunction, adipocyte pathophysiology, obesity and insulin resistance. Additionally, irregular ovarian AGE signaling might in part explain the abnormal ovarian histology observed in women with PCOS. The ovarian dysfunction due to AGEs in women without PCOS suggests a role for the AGE-RAGE system in the ovarian follicular environment, and might relate to assisted reproduction technology outcome and measures of ovarian reserve.The body of literature currently available limits these findings. The results obtained from granulosa cell lines and animal models may not fully extrapolate to humans.This review underscores a critical need to unveil the exact mechanistic actions of AGEs in reproductive physiology and more specifically the hypothalamic-pituitary-ovarian axis. AGE inhibitors might present an emerging therapeutic approach with significant applications in the context of PCOS and infertility.American Society for Reproductive Medicine New Investigator Award and University of Vermont College of Medicine Internal Funds. No competing interests.