Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome

Abstract

Purpose To explore the relationships between the soluble receptor for advanced glycation endproducts (sRAGE) and the outcome parameters following in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) and investigate the protective effect of sRAGE in PCOS development regarding inflammation. Methods We conducted a prospective analysis of a subsample of 74 participants from the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University. We quantified sRAGE, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), interleukelin-6 (IL-6), and C-reactive protein (CPR) protein levels in the follicular fluid from 39 PCOS and 35 non-PCOS reproductive-age women. sRAGE and VEGF, TNF-α, IL-6, and CRP in follicular fluid aspirated without blood were measured by ELISA. Results sRAGE concentrations in the follicular fluid were significantly lower in the PCOS group compared to those in the control group, while VEGF, TNF-α, IL-6, and CRP concentrations were significantly higher in the PCOS group than in the control group (P < 0.05). sRAGE was significantly, inversely correlated with the total dose of gonadotropin (Gn) in the PCOS group undergoing IVF treatment (r = −0.451, P = 0.004). After adjusting for age and Gn dose (in international units used per cycle), sRAGE protein levels in the follicular fluid were significantly, inversely related to VEGF (r = −0.378, P = 0.018), TNF-α (r = −0.450, P = 0.004), IL-6 (r = −0.455, P = 0.004), and CRP (r = −0.375, P = 0.019). Conclusion sRAGE in the follicular fluid might exert a protective effect against the inflammatory action of PCOS development.

Clinical and Radiographic Peri-Implant Parameters and Whole Salivary Interleukin-1β and Interleukin-6 Levels among Type-2 Diabetic and Nondiabetic Patients with and without Peri-Implantitis

“…A state of chronic hyperglycemia has been associated with increased formation of advanced glycation end produts (AGE) and their accumulation in tissues including those of the oral cavity [25]. It has been reported that increased interactions between AGE and their receptors are associated with an increased severity of tissue inflammation and raised levels of proinflammatory cytokines in saliva, follicular fluid, and serum [26][27][28]. As all of the patients with T2DM included in the present study had HbA1c levels higher than 8%, it is likely that there was an increased expression of AGE and interactions between AGE and receptor of AGE among individuals in group 2 (regardless of the presence or absence of peri-implantitis) compared to group 1.…”

sRAGE downregulates the VEGF expression through EGF-like growth factor signal pathway in PCOS ovarian granulosa cells

“…Interestingly, we have found that follicular fluid sRAGE levels were negatively correlated with VEGF in PCOS [9] . EGF-like growth factors, amphiregulin (AREG), betacellulin (BTC), epiregulin (EREG) can bind and activate epidermal growth factor receptor (EGFR) [10,11] .…”

“…To date, emerging evidences have supported that PCOS was related to hyperandrogenism, insulin resistance and chronic inflammation [19] . Our previous study shown that sRAGE concentrations were decreased in the follicular fluid of PCOS patients, and these sRAGE were inversely associated with VEGF, TNF-α, IL-6, and CRP protein levels [9] . According to Boulanger, the activation of AGEs-RAGE axis in human peritoneal mesothelial cells can induce the release of VEGF and subsequently the formation of capillary tubes, while anti-receptor for AGEs (RAGE) antibody reduced capillary tube formation [20] .…”

sRAGE Downregulates the VEGF Expression in PCOS Ovarian Granulosa Cells

“…One research supported our point that sRAGE could represent as a biomarker and a potential therapeutic target for ovarian dysfunction in PCOS [8] . Interestingly, we have found that follicular uid sRAGE levels were negatively correlated with VEGF in PCOS [9] . EGF-like growth factors, amphiregulin (AREG), betacellulin (BTC), epiregulin (EREG) can bind and activate epidermal growth factor receptor (EGFR) [10] .…”

“…To date, emerging evidences have supported that PCOS was related to hyperandrogenism, insulin resistance and chronic in ammation [19] . Our previous study shown that sRAGE concentrations were decreased in the follicular uid of PCOS patients, and these sRAGE were inversely associated with VEGF, TNF-α, IL-6, and CRP protein levels [9] . According to Boulanger, the activation of AGEs-RAGE axis in human peritoneal mesothelial cells can induce the release of VEGF and subsequently the formation of capillary tubes, while anti-receptor for AGEs (RAGE) antibody reduced capillary tube formation [20] .…”