The Effect Of ERK Inhibitor FR180204 On The Expression Of VEGF In Ovarian Granule Cells Of Patients With Polycystic Ovary Syndrome

Objective Study the relationship between the excessive expression of vascular endothelial growth factor(VEGF)witch belongs to the ovaries of polycystic ovary syndrome(PCOS)patients and the abnormal activation of Mitogen-activated protein kinase(MAPK)/extracellular signal regulating kinase(ERK)pathway.And discuss the mechanism of PCOS on the molecular level.Methods The ovum follicular granulosa cells were collected in retrieved oocyte day from PCOS patients and the normal control group patients(n=20)who were under the treatment of in vitro fertilization and embryo transfer in the reproductive center of the Affiliated Hospital of Qiingdao University during April to July in 2017.Then purified and cultivated the granulosa cells.In addition,ERK inhibitors were added to the experimental group at the right time.The phosphorylation of ERK and the expression of VEGF was measured by Western blot..Result(1)The age,infertile years,body mass index(BMI),basal estradiol(b E2),follicle stimulating hormone(b FSH),prolactin(b PRL),the starting amount of gonadotropin(Gn),and total Gn dosage in group PCOS and N-PCOS were analyzed by single factor analysis of variance,and the difference was not statistically significant(P > 0.05).(2)The basal luteinizing homone(b LH),testosterone(b T)and the number of acquired eggs were significantly higher in PCOS group than in N-PCOS group,and the difference was statistically significant(P<0.05).(3)The degree of ERK phosphorylation and the expression of VEGF in group PCOS,group N-PCOS and group PCOS+IN were compared.ERK serine phosphorylation and VEGF expression in PCOS group were higher than those in N-PCOS group,the difference was statistically significant(P < 0.05).After treatment with FR180204,the level of ERK serine phosphorylation and VEGF expression in PCOS+IN group were all lower than those in PCOS group,the difference was also statistically significant(P < 0.05),though it is still higher than the N-PCOS group.Conclusion The phosphorylation of ERK serine and the expression level of VEGF were decreased,after the PCOS ovarian granulosa cells were treated with MAPK/ERK pathway specific blocker FR180204.It suggests that the VEGF overexpression is improved after blocking the MAPK/ERK pathway.It is suggested that ovarian overexpression of VEGF in PCOS patients is associated with abnormal activation of MAPK/ERK pathway.Significance Over expression of VEGF in ovarian granulosa cells of PCOS patients may be related to abnormal activation of MAPK/ERK in insulin pathway.The increased VEGF may be involved in and promote a series of pathological changes of PCOS.At present,most scholars believe that the occurrence of insulin resistance(IR)is due to the dysfunction of the phosphatidylinositol 3 kinase(PI3K)pathway and the abnormal activation of the MAPK pathway in the insulin pathway.It is speculated that the over expression of VEGF in ovary of PCOS patients is related to IR,and the pathogenesis of PCOS is discussed from molecular level.It is suggested that we can reduce VEGF secretion by improving the IR of PCOS patients,and then improve the clinical symptoms of ovarian polycystic change,ovulation disorder,abnormal blood flow signal and ovarian hyperstimulation(OHSS).