Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS?

Abstract

PCOS is the most common cause of anovulation in reproductive-aged women with 70% experiencing ovulatory problems. Advanced glycation end products are highly reactive molecules that are formed by non-enzymatic reactions of sugars with proteins, nucleic acids and lipids. AGEs are also present in a variety of diet where substantial increase in AGEs can result due to thermal processing and modifications of food. Elevation in bodily AGEs, produced endogenously or absorbed exogenously from high-AGE diets, is further exaggerated in women with PCOS and is associated with ovulatory dysfunction. Additionally, increased expression of AGEs as pro-inflammatory receptors in the ovarian tissue has been observed in women with PCOS. In this review, we summarize the role of dietary AGEs as mediators of metabolic and reproductive alterations in PCOS. Once a mechanistic understanding of the relationship between AGEs and anovulation is established, there is a promise that such knowledge will contribute to the subsequent development of targeted pharmacological therapies that will treat anovulation and improve ovarian health in women with PCOS.

Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS

“…PCOS is the most common cause of anovulation in reproductive-aged women [2] and has been associated with different adverse outcomes in women undergoing assisted reproduction, such as low fertilization rate, low number of good quality embryos, and high spontaneous abortion rates after ovulation induction and after in vitro fertilization (IVF) treatments [3][4][5]. Advanced glycation end products (AGEs) are highly reactive pro-inflammatory molecules that are physiologically formed by non-enzymatic alteration of proteins, lipids, and nucleic acids by glucose or by ingestion of a variety of fast foods [6,7]. AGEs constitute a heterogeneous group of compounds of more than 20 members.…”

Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS

“…These studies substantiate the association between AGEs and hyperandrogenism in PCOS. Accumulating evidence has demonstrated that dietary modification with intake of diet containing low AGEs can reduce the concentration of plasma bioavailable testosterone and can modify PCOS phenotypes [ 21 , 79 ].…”

“…AGEs, also called “glycotoxins,” are the byproducts of Maillard reaction in which the carbonyl group of carbohydrates non-enzymatically interacts with lipids or with the amino group in proteins [ 20 ]. AGEs can be formed endogenously by the body or absorbed exogenously by intake of diet containing high levels of AGEs (such as fast-food diet) or by smoking [ 21 ]. AGEs are known to play a role in the pathogenesis of different diseases such as diabetes, aging, Alzheimer disease, atherosclerosis, renal disease, and recently PCOS by causing oxidative stress, altering enzymatic activities, affecting cytotoxic pathways, or damaging nucleic acids [ 19 , 22 , 23 ].…”

Polycystic ovary syndrome and environmental toxins

“…AGEs have also been shown to disrupt oocyte development, growth, and maturation in preovulatory follicles, likely via the ERK1/MAPK signaling pathways (107,108). Chronic inflammation and increased oxidative stress (53) are considered the link between mechanisms via which AGEs are linked with reproductive consequences of PCOS.…”