Studies Of SRAGE And GLUT4 In Follicular Fluid Of PCOS Patients With Or Without Insulin Resistance

Polycystic ovary syndrome(PCOS)is one of the most common endocrine diseases in women,the prevalence of between 6%and 10%.Its pathogenesis is still unknown.It is a metabolic disorder syndrome characterized by hyperandrogenemia,polycystic changes in the ovary,insulin resistance(IR)and thin ovulation.Current studies believe that IR is the main pathogenic factor causing metabolic disorder in PCOS patients,and hyperandrogenism(HA)and IR can affect each other and jointly aggravate the pathological progress of PCOS.Abnormal insulin signaling pathway is an important link that leads to decreased insulin sensitivity and IR.Glucose transporter 4(GLUT4)is a kind of protein formed by Glucose carrier.As a kind of Glucose transporter,GLUT4 plays a key role in Glucose metabolism.Although reduced GLUT4 levels are not a direct cause of insulin resistance in obese and diabetic patients,there is a consensus that increasing GLUT4 expression in human fat cells can improve insulin resistance by reducing insulin sensitivity.Advanced glycation endproducts(AGEs)are a group of heterogeneous proteins gradually formed after non-enzymatic reactions between aldehydes or ketones and amino groups of various proteins.When pathological changes such as cell damage,hyperglycemia,obesity,oxidative stress,and hypoxia occurred,AGEs and their precursors increased.The accumulation of AGEs is associated with a variety of diseases,such as type 2 diabetes mellitus(T2DM),metabolic syndrome,cardiovascular disease,hypertension,and PCOS.RAGE(receptor for advanced glycation end-products),as a AGE,receptor,is an immunoglobulin superfamily receptor.The AGE-RAGE axis mediates insulin resistance and induces inflammation in polycystic ovary.Solube receptor for advanced glycation end products is the RAGE of endogenous secretory type,which may be by combining cycle and as bait competitive inhibition AGE-RAGE,not mediated AGE-RAGE shaft caused by pathological process,it can act as "protective factors" suppress many kinds of disease development,therefore is called "decoy receptor".The study of sRAGE in reproductive system was reported in 2014.Some scholars found that the concentration of sRAGE in follicular fluid was closely related to ovarian reserve function,suggesting that it might be involved in follicular growth and embryonic development.Previous studies by our group have found that high sRAGE concentration in follicular fluid can predict better pregnancy outcomes in women of childbearing age assisted with IVF(in vitro fertilization-embryo transfer),and low sRAGE expression in PCOS patients.Since IR is an important link in the occurrence of PCOS,this study will investigate whether the expression level of sRAGE in follicular fluid is different in PCOS patients with or without IR.In addition,in the ovarian granulosa cell line of KGN,the high expression of AGEs can be involved in the generation of IR by mediating the PI3K/AKT pathway to reduce the generation of GLUT4 and thus participate in the generation of IR.Therefore,this research group expects to further investigate whether there is an association between sRAGE and the expression level of GLUT4 in the follicular fluid of patients with PCOS and IR.In conclusion,by detecting the expression of GLUT4 in ovarian granulosa cells in follicular fluid,this study aims to further study the correlation between sRAGE level in follicular fluid and GLUT4 in patients with PCOS and insulin resistance,and to provide a preliminary research basis for the prevention and treatment of PCOS from the perspective of protective mechanism.Objective1.To investigate whether the expression of sRAGE and GLUT4 in follicular fluid was different in PCOS patients with or without insulin resistance;2.Whether there is a correlation between the expression levels of sRAGE and GLUT4 in follicular fluid of PCOS patients with IR.Materials and methods1.Collection patients who received ivf-et assisted pregnancy treatment only for PCOS in the reproductive center of the third affiliated hospital of zhengzhou university from March 2018 to September 2018 were selected.According to the PCOS Rotterdam diagnostic criteria,Homeostasis model assessment of insulin resistance was used as a simple model to evaluate insulin resistance.PCOS patients were divided into 27 patients in the insulin resistance group and 29 patients in the non-insulin resistance group,The levels of sRAGE in follicular fluid of PCOS-IR group and PCOS-non-IR group were measured by ELISA,and the level of GLUT4 in ovarian granulosa cells in follicular fluid of both groups was detected by Western Blot.2.This study met the standards of the hospital ethics committee,and was approved by the ethics committee.The informed consent of the sick was obtained,and a written informed consent was signed.Results1.There were no statistically significant differences in age,BMI,FSH,LH,LH/FSH,T,E2,and infertility years in patients with polycystic ovarian insulin resistance and non-insulin resistance(p>0.05).2.The sRAGE level in the follicular fluid of the PCOS-IR group was lower than that in the PCOS-non-IR group,and the difference was statistically significant(p<0.05);the GLUT4 level in the follicular fluid of the PCOS-IR group was lower than that in the PCOS-non-IR group,and the difference was statistically significant(p<0.05).3.SRAGE level in follicular fluid was positively correlated with GLUT4 level in pcos-ir group(r=0.407,p<0.05).ConclusionsCompared with the PCOS-non-IR group,the PCOS-IR group had low expression of sRAGE and GLUT4 in the follicular fluid,and sRAGE and GLUT4 levels were positively correlated.