Clinical and Experimental Reproductive Medicine  2013;40(1):12-22

doi:10.5653/cerm.2013.40.1.12

Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion.

Kyu Hwan NA 1 ; Jong Ho CHOI ; Chun Hyung KIM ; Kwang Soo KIM ; Gi Jin KIM

Affiliations

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Keywords

Placenta; Pre-eclampsia; Norepinephrine transporter; Enzyme-linked immunosorbent assay; Small interfering RNA

Country

Republic of Korea

Language

English

Abstract

OBJECTIVE: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. METHODS: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. RESULTS: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. CONCLUSION: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development.