Hypoxia-Inducible Factor 1α And Epithelial- Mesenchymal Transition Markers In Human Adenomyosis

ObjectiveTo investigate the different expresstionof hypoxia-inducible factor 1αand EMT markers in eutopic endometria and ectopic endometria,and normal endometria.The aim of this study is to explor how the hypoxia-inducible factor 1α and Epithelial–Mesenchymal Transition markers express in human adenomyosis,and to provide a basis for further exploring the mechanism of hypoxia inducible factor HIF-1 alpha in the epithelial mesenchymal transition of adenomyosis.MethodIn order to determine how HIF-1α and EMT markers express in cases of human adenomyosis,IHC analysis of E-cadherin,N-cadherin and vimentin,Transforming growth factorβ1,β-catenin,in normal endometrium,eutopic endometrium and ectopic endometrium were performed with samples from 50 patients with adenomyosis,and 40 normal endometria as control cases.Meanwhile RT-PCR ananlysis of these factors in normal endometrium,eutopic endometrium and ectopic endometrium were performed with samples from 20 patients with adenomyosis,and 20 normal endometria as control cases.Results1.HIF-1a was detected in the nuclei of epithelial and stromal cells.Epithelial HIF-1α expression was significantly greater compared with that of stromal cells.Epithelial HIF-1α expression was significantly greater in adenomyosis samples compared with those from normal endometrial(P﹤0.01).Compared with normal endometria,HIF-1α was also detected in both the endothelial cells of vessels in the stromal cells and the smooth muscle cells surrounding the ectopic adeomyosis(P﹤0.01).E-cadherin expression in adenmyosis was significantly lower than the control group(P ﹤ 0.01).N-cadhrin and Vimentin expression in the experimental group was significantly greater than that in the control group.β-catenin expression in eutopic endometrium was lower the control group(P﹥0.05),but significantly greater in the ectopic endometrium.The expression of TGF-β1 in ectopic endometrium was significantly greater than that in the eutopic endometrium and nomal endometrial.HIF-1α was negatively correlated with E-cadherin(r=-0.832,P﹤0.01),but was positively correlated with N-cadherin(r=0.781,P﹤0.01).HIF-1α was incorrelated with β-catenin、Vimentin and TGF-β1.2.RT-PCR: Compared with normal endometrium,the expression level of HIF-1 in experimental group was increased(P﹤0.01).The expression level of E-cadherin in the experimental group was decreased(P﹤0.01),and the-catenin in the experimental group was slightly down regulated(P ﹥ 0.05),which was significantly increased in the experimental group(P﹤0.01).The expression of N-cadherin,Vim,TGF-beta 1 in the experimental group increased(P﹤0.01).Conclusions1.Expression of HIF-1 in endometrium of experimental group was significantly higher than the control group,RT-PCR results showed that HIF-1 alpha in the experimental group endometrium was significantly increased,suggesting that may be involved in the pathogenesis of adenomyosis,and may be related to the occurrence and development of uterine adenomyosis.The expression of HIF-1 was significantly higher than that of the control group in the experimental group,suggesting that the change of the microenvironment of adenomyosis may provide a prerequisite for the invasion,implantat ion and growth of endometrium.2.The mRNA and protein of interstitial epithelial markers E-cadherin,N-cadherin,and Vimentin were changed in the experimental group,suggesting that there may be an epithelial mesenchymal transition process.Beta-catenin and TGF-beta1 in the experimental group were higher than those in the control group,suggesting that the two may be involved in the process of epithelial mesenchymal transition of adenomyosis,and promote the development of adenomyosis.3.The expression of HIF-1 was negatively correlated with the expression of E-cadherin and positively correlated with the expression of N-cadherin.It is suggested that HIF-1 may regulate the expression of EMT related proteins,and then regulate the EMT process of endometrium,and promote the occurrence of adenomyosis.HIF-1 has no correlation with beta-catenin,Vimentin,TGF-beta1,suggesting that beta-catenin,Vimentin,TGF-beta 1 may be involved in the pathogenesis of adenomyosis through other pathways.