Effect Of Metformin On Serum FOXO1,GLUT4,TNF-? And FOXO1 Expression In Endometrium Of PCOS Patients

ObjectionTo understand the serum levels of Forkhead box-containing protein O subfamily-1(FOXO1),glucose transporter 4(GLUT4)and tumor necrosis factor?(TNF-?)in control group,obese polycystic ovary syndrome(PCOS)and non-obese PCOS groups,and metformin intervention groups,and to explore the correlation of all the indexes in the serum.1.To explore the expression and localization of FOXO1 protein in endometrium of different groups during the implantation window.MethodsFrom January 2017 to November 2017,the patients with PCOS who were diagnosed with Rotterdam criteria consensus were enrolled in the Reproductive Center of our hospital as the experiental group,and divided into obese group and non-obese group according to BMI?28kg/m~2.The control group was infertility due to fallopian tube factors in the same period.The metformin group were PCOS patients who received oral metformin for 4 weeks.In the PCOS group and the control group,5 ml of venous blood was collected during 2-5 day of menstruation or progesterone withdrawal bleeding phase and without dominant follicles by transvaginal sonography examination,The metformin group was collected 5 ml venous blood during 2-5 day of menstruation or progesterone withdrawal bleeding phase after the end of medication,and without dominant follicles by transvaginal sonography examination.Then the concentration of follicle stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),fasting blood glucose(FBG)and fasting insulin(FIN),FOXO1,GLUT4 and TNF-?were measured in serum.All groups were cancelled transplantation of this cycle after ovulation 6-8 days later,then collectted some endometrial tissue used a disposable S-type uterine tissue aspiration tube,Immunohistochemistry was used to detect the expression of FOXO1 in the endometrium of the three groups.ResultsIn this study,13 serum samples were collected from obesity PCOS,17 serum samples were collected from non-obesity PCOS,30 serum samples were collected from metformin group and control group respectively.Compared with the control group,FBG,FIN and HOMA-IR in obesity PCOS group were significantly higher than those in control group(P<0.05);BMI,LH,T,FBG,FIN and HOMA-IR in non-obesity PCOS group were significantly higher than those in control group(P<0.05);BMI,FBG,FIN,HOMA-IR in Metformin group were lower than the obesity PCOS group,the difference was statistically significant(P<0.05).The concentrations of FOXO1 and TNF-?in obesity PCOS group were significantly higher than those in control group(P<0.05),and the GLUT4 concentrations in PCOS obesity group were lower than those in control group(P<0.05).The concentrations of FOXO1 and TNF-?in metformin group were lower than those in obesity PCOS group,but still higher than those in control group(P>0.05),while the GLUT4 concentrations in metformin group were higher than those in obesity PCOS group,but still lower than those in control group(P>0.05).There was a positive correlation between the serum concentration of FOXO1 and TNF-?in the PCOS group(r=0.767,P<0.05),there was a positive correlation between FOXO1 and TNF-?(r=0.540,P<0.05),but negative correlation with GLUT4(r=-0.395,P<0.05)in metformin group.There was no linear correlation between serum concentration of FOXO1 and GLUT4 and TNF-?in the control group.In the PCOS group and metformin group,there was a negative correlation between serum concentration of TNF-?and GLUT4(r=-0.475,P<0.05;r=-0.463,P<0.05),in the control group,serum concentration of TNF-?and GLUT4 did not have correlation.In this study,we respectively collected endometrial tissue from 9 cases in control group,10 cases in PCOS group and 7 cases in metformin group at the implantation window,The expression of FOXO1 was expression in the glandular epithelial cells of endometrium in all the group,The positive expression of FOXO1 in PCOS group was higher than that in the control group,and the difference was statistically significant(P<0.05).ConclusionThe levels of sex hormones and blood glucose in obesity PCOS patients were changed compared with those in non-PCOS and non-obesity PCOS patients.The levels of serum FOXO1 and TNF-?were elevated,but GLUT4 levels were decreased in obesity PCOS patients,and the level of FOXO1 is positively correlated with TNF-?and negatively correlated with GLUT4,suggesting that obesity affects the occurrence of low-grade chronic inflammation and insulin resistance in PCOS patients and the occurrence of low-grade chronic inflammation and insulin resistance could be related to the change of FOXO1.The increase of FOXO1 protein during implantation window period might be one of reasons for the decrease of endometrial receptivity.Metformin could treat PCOS patients by regulating serum hormones,FOXO1,TNF-?,GLUT4 levels and changing the expression of FOXO1 in endometrium.