title: Study on the expressions of PHD and HIF in placentas from normal pregnant women and patients with preeclampsia.
abstract: OBJECTIVE
  To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia.
  
  
  METHODS
  Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; middle pregnancy group (MP), 9 cases; late pregnancy group (LP, or control group), 12 cases; preeclampsia (PE) group, 20 cases; gestational hypertension group (GH), 10 cases. The mRNA expressions of PHD-1 and -2 and -3 in placentas from all the subjects were assessed by in situ hybridization and Real-time PCR. The expressions of HIF-1α and -2α in placentas from different groups were assessed by immunohistochemistry and western blot.
  
  
  RESULTS
  PHD-1,-2 and -3 mRNA were mainly expressed in cytoplasm of trophoblast, especially strongly expressed in extravillous trophoblast. During the progress of pregnancy, the expression of PHD-1 increased significantly (R=0.616, P<0.001). The PHD-1mRNA expression in placentas from PE group decreased significantly compared with that from control group, P<0.05. A significant direct correlation between the PHD-1 mRNA expression in placentas from PE group and their placenta weight was found (R=0.457, P<0.05). The HIF-2α, not the HIF-1α expression, from PE group was significantly higher than that from control group, P<0.01; The HIF-2α expression in trophoblast from PE was inversely correlated to the date of the onset of the disease (R=-0.730, P<0.01).
  
  
  CONCLUSIONS
  PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2α. The overly activated hypoxic response pathway of trophoblast in preeclamptic placenta, which is manifested as the result of HIF-2α over-expression, is the key point to hypoxic dysfunction of trophoblast.
authors.affiliation: 1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: 2. Shanghai Institute of Immunology, Shanghai, 200025, China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: 1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China;
authors.forename: Qi-De
authors.initials: QD
authors.lastname: Lin
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy; D014327:Trophoblasts / Q000201:enzymology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C447780:EGLN2 protein, human
keywords: Hypoxia-inducible factor; Preeclampsia; Trophoblast.; hypoxia-inducible factor prolyl 4-hydroxylase