Clin Exp Reprod Med.  2013 Mar;40(1):12-22. 10.5653/cerm.2013.40.1.12.

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

• Na KH
• Choi JH
• Kim CH
• Kim KS
• Kim GJ

• KMID: 1430078
• DOI: http://doi.org/10.5653/cerm.2013.40.1.12

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.

Keyword

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

MeSH Terms

Blotting, Western
Enzyme-Linked Immunosorbent Assay
Female
Humans
Matrix Metalloproteinase 9
Norepinephrine
Norepinephrine Plasma Membrane Transport Proteins
Placenta
Placentation
Plasma
Pre-Eclampsia
Pregnant Women
RNA
RNA, Messenger
RNA, Small Interfering
Transfection
Trophoblasts
Up-Regulation
Matrix Metalloproteinase 9
Norepinephrine
Norepinephrine Plasma Membrane Transport Proteins
RNA
RNA, Messenger
RNA, Small Interfering