Decreased levels of sRAGE in follicular fluid from patients with PCOS

Abstract

This study aimed to explore the association between soluble receptor for advanced glycation end products (sRAGE) levels in follicular fluid and the number of oocytes retrieved and to evaluate the effect of sRAGE on vascular endothelial growth factor (VEGF) in granulosa cells in patients with polycystic ovarian syndrome (PCOS). Two sets of experiments were performed in this study. In part one, sRAGE and VEGF protein levels in follicular fluid samples from 39 patients with PCOS and 35 non-PCOS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 10 patients with PCOS and cultured. VEGF and SP1 mRNA and protein levels, as well as pAKT levels, were detected by real-time PCR and Western blotting after cultured cells were treated with different concentrations of sRAGE. Compared with the non-PCOS patients, patients with PCOS had lower sRAGE levels in follicular fluid. Multi-adjusted regression analysis showed that high sRAGE levels in follicular fluid predicted a lower Gn dose, more oocytes retrieved, and a better IVF outcome in the non-PCOS group. Logistic regression analysis showed that higher sRAGE levels predicted favorably IVF outcomes in the non-PCOS group. Multi-adjusted regression analysis also showed that high sRAGE levels in follicular fluid predicted a lower Gn dose in the PCOS group. Treating granulosa cells isolated from patients with PCOS with recombinant sRAGE decreased VEGF and SP1 mRNA and protein expression and pAKT levels in a dose-dependent manner.

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

“…sRAGE can be detected in the blood and follicular fluid [17]. sRAGE is considered an antiinflammatory receptor because it binds circulating AGEs, thus preventing their binding to RAGE, leading to the alleviation of the adverse intracellular events of the pro-inflammatory AGE-RAGE axis [16,18,19]. Recent studies have shown that serum and follicular fluid sRAGE levels were lower in women with PCOS patients and inversely correlated with body mass index (BMI) and insulin resistance [17,19,20].…”

“…sRAGE is considered an antiinflammatory receptor because it binds circulating AGEs, thus preventing their binding to RAGE, leading to the alleviation of the adverse intracellular events of the pro-inflammatory AGE-RAGE axis [16,18,19]. Recent studies have shown that serum and follicular fluid sRAGE levels were lower in women with PCOS patients and inversely correlated with body mass index (BMI) and insulin resistance [17,19,20]. We have shown in women without PCOS that follicular fluid sRAGE levels positively correlated with follicular fluid anti-Mullerian hormone (AMH) levels, one of the best markers of ovarian reserve, and also predicted the number of oocytes retrieved following controlled ovarian stimulation (COS), indicating that sRAGE could potentially be used as a marker of ovarian reserve [21].…”

“…We have shown in women without PCOS that follicular fluid sRAGE levels positively correlated with follicular fluid anti-Mullerian hormone (AMH) levels, one of the best markers of ovarian reserve, and also predicted the number of oocytes retrieved following controlled ovarian stimulation (COS), indicating that sRAGE could potentially be used as a marker of ovarian reserve [21]. Higher sRAGE levels in the follicular fluid have been shown to be associated with favorable IVF outcome in terms of requiring lower doses of gonadotropins for COS, higher number of retrieved oocytes, and better pregnancy rates [19]. On the other hand, another study demonstrated that higher follicular fluid sRAGE levels were associated with poor embryo quality after IVF [22].…”

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

“…sRAGE acts as a decoy that interrupts adverse intracellular signaling caused by the AGE-RAGE axis and is not only a biological marker that reflects pathological changes, but is also a protective factor that delays the occurrence of many diseases [6] . Our previous study found that the follicular fluid sRAGE has a positive correlation with ovarian reservation and decreased in PCOS compared with women without PCOS [7] . One research supported our point that sRAGE could represent a biomarker and a potential therapeutic target for ovarian dysfunction in PCOS [8] .…”

sRAGE Downregulates the VEGF Expression in PCOS Ovarian Granulosa Cells

“…sRAGE acts as a decoy that interrupts adverse intracellular signaling caused by the AGE-RAGE axis and is not only a biological marker that re ects pathological changes, but is also a protective factor that delays the occurrence of many diseases [6] . Our previous study found that the follicular uid sRAGE has a positive correlation with ovarian reservation and decreased in PCOS compared with women without PCOS [7] . One research supported our point that sRAGE could represent as a biomarker and a potential therapeutic target for ovarian dysfunction in PCOS [8] .…”