Int J Biol Sci 2014; 10(3):278-284. doi:10.7150/ijbs.6375

Research Paper

Study on the Expressions of PHD and HIF in Placentas from Normal Pregnant Women and Patients with Preeclampsia

Wei Liu1, Shu-Jun Wang2, Qi-De Lin1✉

1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China;
2. Shanghai Institute of Immunology, Shanghai, 200025, China.

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.

Keywords: Preeclampsia, Hypoxia-inducible factor, hypoxia-inducible factor prolyl 4-hydroxylase, Trophoblast.

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How to cite this article:
Liu W, Wang SJ, Lin QD. Study on the Expressions of PHD and HIF in Placentas from Normal Pregnant Women and Patients with Preeclampsia. Int J Biol Sci 2014; 10(3):278-284. doi:10.7150/ijbs.6375. Available from http://www.ijbs.com/v10p0278.htm