The Effect Of HIF-2 On The Development Of Placenta And The Etiology Of Pregnancy Induced Hypertension

Objective: [1] To investigate the effect of HIF-2 on the development of placenta and the possible mechanism.[2] To explore the role of HIF-2 in the process of pathophysiology of pregnancy induced hypertension (PIH) and its possible mechanism.Method: [1] The early trimester villous explants and early embryo were incubated in vitro and the placental tissues were obtained from normal term pregnant woman by selective cesarean. The mRNA expression levels of HIF-2 α in explants and in placentas were examined by RT- PCR and real-time PCR, respectively. The expression of HIF-2 α protein in placentas was analyzed by Western blot, while the immunolocalization of HIF-2 α protein in villous explants was determined by immunohistochemistry. [2] 10 cases of placental tissues were obtained from women with pre-eclampsia and 10 control cases from age-matched women with normal pregnancy. The mRNA expression of HIF-2 α and VEGF were examined by real time PCR. The expression of HIF-2 α protein was analyzed by Western blot. The immunoactivity of HIF-2 α protein in PIH placentas was detected by histochemical analysis. [3] Theearly trimester villous explants and Be Wo cells were divided into four groups: normixa, hypoxia, sense oligonucleotide and antisense oligonucleotide , then incubated under different conditions in vitro, respectively. The expression of HIF-2 α protein was analyzed by Western blot, and the mRNA expression of HIF-2 α and VEGF were performed by real-time PCR. After HIF-2 α was blocked by its antisense oligonucleotide, the effect of hypoxia on the expression of VEGF mRNA was observed.Results: (l)HIF-2 α mRNA was detected in villous explants and in placentas from normal pregnancy, as well as in early embryo. (2) The immunoactivity of HIF-2 protein was localized in the cytoplasm of syncytiotrophoblast in villous explants. (3 ) The mRNA expression of HIF-2 α and VEGF are higher significantly in PIH placentas than in age-matched normal placentas, as well as the expression of HIF-2 α protein. (4) The immunoactivity of HIF-2 α protein was mainly located in the cytoplasm of syncytiotrophoblast and fetoplacental vascular endothelium in the PIH placentas. (5) Compared with normixa group, the expression of HIF-2 α mRNA and HIF-2 α protein in hypoxia group were increased significantly in early villous explants and Be Wo cells, as well as the expression of VEGF mRNA (P<0.05), while that in antisense group was not changed (P>0.05) .When HIF-2 α was blocked by its anti-sense oligonuleotide, the mRNA expression level of HIF-2 α and VEGF under hypoxia condition were decreased significantly than that in sense group, as well as the expression of HIF-2 protein.Conclusions: [1] The expression of HIF-2 α in early trimester villous explants may be related to the development of placentas, while the expression of HIF-2 α in placentas from normal term pregnancy may be involved in maintaining the vascular penetrability [2] The expression of HIF-2 and VEGF...