Endocrine Disorders And Female Infertility:Pathophysiological Study Of Phoenixin-14 And Estradiol Levels

1.Background:Polycystic ovary syndrome(PCOS)is commonly characterized by obesity,insulin resistance(IR),hyperandrogenemia and hirsutism.Following the reported relationship between phoenixin-14 and gonadotropin production in rat hypothalamic-pituitary-gonadal axis,the present study was designed to investigate the circulating levels of phoenixin-14 and their associations with the levels of sex hormones including luteinizing hormone(LH),follicular stimulating hormone(FSH),estradiol(E2),progesterone(P4)and total testosterone(TT)in PCOS patients.Methods:A total of 41 women with diagnosed PCOS using Rotterdam criteria and 37 healthy individuals were enrolled in the study.Results:Serum phoenixin-14 level in PCOS patients(n=41)was 0.515±0.044 ng/mL,significantly higher than that in healthy controls(0.289±0.046 ng/mL,n=37).PCOS patients had higher serum LH,dehydroepiandrosterone and fasting blood glucose levels,and higher index of homeostasis model of assessment-IR than those in healthy women.Correlation analysis showed significantly positive correlations of phoenixin-14 with LH,FSH,TT,P4,body mass index and nesfatin-1 levels,and significantly negative correlations with E2 and serum insulin(FSI)levels,respectively.Conclusions:These results indicate that,compared to control women,PCOS patients had significantly increased serum phoenixin-14,LH and androgen levels.The positive correlations of phoenixin-14 levels with LH and TT levels suggest a possible role of phoenixin-14 in the development of PCOS.2.Background:Previous studies have shown that increasing estradiol concentrations had a toxic effect on the embryo and were deleterious to embryo adhesion.In this study,we evaluated the physiological impact of estradiol concentrations on endometrial cells to unveil that serum estradiol levels probably targeted endometrium in controlled ovarian hyperstimulation(COH)protocols.Methods:An attachment model of human choriocarcinoma(JAr)cell spheroids to receptive-phase endometrial epithelial cells and Ishikawa cells treated with different estradiol(10-9M or 10-7M)concentrations was developed.Differentially expressed protein profiling of the Ishikawa cells was performed by proteomic analysis.Results:Estradiol at 10-7M demonstrated a high attachment rate of JAr spheroids to the endometrial cell monolayers.Using iTRAQ coupled with LC-MS/MS,we identified 45 differentially expressed proteins containing 43 significantly up-regulated and 2 down-regulated proteins in Ishikawa cells treated with 10-7M estradiol.Differential expression of C3,plasminogen and kininogen-1 by western blot confirmed the proteomic results.C3,plasminogen and kininogen-1 localization in human receptive endometrial luminal epithelium highlighted the key proteins as possible targets for endometrial receptivity and interception.Ingenuity pathway analysis of differentially expressed proteins exhibited a variety of signaling pathways,including LXR/RXR activation pathway and acute phase response signaling,and,upstream regulators(TNF,IL6,Hmgn3,and miR-140-3p)associated with endometrial receptivity.Conclusion:The observed estrogenic effect on differential proteome dynamics in Ishikawa cells indicates that the human endometrium is the probable target for serum estradiol levels in COH cycles.The findings are also important for future functional studies with the identified proteins that may influence embryo implantation.