Correlation Of CFTR In The Pathogenesis Of Polycystic Ovary Syndrome

Polycystic ovary syndrome(PCOS)is one of the common causes of female infertility and a complex endocrine and metabolic disorder common in women of gestational age,usually due to ovulation disorder or non-ovulation and hyperandrogenism Is the main feature.The clinical manifestations are mainly irregular menstrual cycle,infertility,hairiness,and acne.The pathogenesis of PCOS is relatively complicated,and the study found that this is a disease caused by the interaction of multiple gene abnormalities and environmental factors.In recent years,changes in the ovarian microenvironment have become a hotspot of research at home and abroad.Dysfunction of ovarian local regulatory factors is considered an important link in the pathogenesis of PCOS.Cystic fibrosis transmembrane transduction factor(CFTR)is a cyclic adenosine phosphate-dependent chloride channel protein that plays an important role in maintaining and stabilizing the steady state of the local liquid microenvironment in the body.The mutation of CFTR gene can caμse its transport dysfunction on cell membrane,and some studies have shown that it is related to some signaling pathways related to cell inflammation and apoptosis.It is currently known that CFTR is expressed in human granulosa cells and is an important local regulator of the ovary.The expression of CFTR was down-regulated in PCOS rat model.CFTR dysfunction can cause cystic fibrosis(CF),and patients with fibrocystic clinical manifestations of delayed puberty,anovulation,ovulation less,amenorrhea are similar to PCOS,thus speculating that CFTR may be involved in inflammation and The process of apoptosis is involved in the pathogenesis of PCOS.Although there have been studies showing that CFTR is expressed in female ovaries,there is no relevant research report on CFTR in the occurrence and development of PCOS,and its impact on ovarian function and the specific mechanism need to be further studied.Objective:To investigate the effects of CFTR on the biological characteristics of hμman ovarian granuloma tumor cells(COV434),such as CFTRinh-172,to investigate the effect of CFTR on ovaries,and to further explore The relevance of the pathogenesis of PCOS provides a new idea for the clinical treatment of PCOS.Methods:The proliferative activity and apoptosis of COV434 cells after adding CFTRinh-172 were detected by MTT method,Western Blot and qRT-PCR respectively,and the expression of cysteine aspartic protease(Caspase-3)protein,cyclooxygenase-2(Cox-2)protein and tumor necrosis factor(TARIL)gene was detected.The statistical results are expressed in Mean ± SEM,using SPSS 22.0 statistical software,after the homogeneity of variance test,μsing One-Way ANOVA analysis,P<0.05 indicates that the difference is statistically significant.Results:1.MTT method.Different concentrations(10μM and 50μM)of CFTRinh-172 acted on COV434 cells until their growth viability decreased(P<0.001),and their growth inhibition was significant with the increase of concentration.The growth inhibition rate of COV434 cells on the third day after CFTRinh-172 treatment was significantly different,and the inhibition rate was significantly positively correlated with the duration of action(P<0.05).2.Western Blot After different concentrations(1μM and 10μM)of CFTRinh-172 acted on COV434,the protein expression of Caspase-3 and COX-2 increased with the increase of concentration.Among them,the protein expression of Caspase-3 was significantly higher than that after 24 hours of culture after 48 hours of culture.3.qRT-PCR.After adding different concentrations(1μM and 10μM)of CFTRinh-172,the 24h expression level of TARIL gene in COV434 was lower than that of the control group,and the inhibitory effect was more significant as the dose increased,with statistical significance(P<0.05).Conclusion:1.CFTRinh-172 has an inhibitory effect on the growth of COV434 cells at different times and at certain concentrations,in a dose-effect relationship.We know that the reduction of granulosa cell proliferation and apoptosis may be the basis of PCOS follicular dysplasia.From this we speculate that the CFTR channel has certain relevance to the pathogenesis of PCOS and is expected to become a potential therapeutic target in the future.2.CFTRinh-172 can promote the expression of Caspase-3 protein and Cox-2 protein in COV434.Activated Caspase-3 is one of the most critical executive molecules in the process of apoptosis.High expression indicates the existence of apoptosis.3.CFTRinh-172 can inhibit TARIL gene expression in COV434.The loss of CFTR function may reduce the expression of TRAIL in granulosa cells,resulting in inflammation in the ovary,which in turn causes PCOS.