Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies.
Pre-eclampsia is one of the most common causes of perinatal and maternal morbidity and mortality. High blood pressure and proteinuria are important clinical signs of pre-eclampsia. Sympathetic overactivity and elevated level of circulating vaso active substances, such as monoamines has been shown. Extracellular concentrations of monoamines are normally kept low by specific transporter proteins of which many are expressed in the placenta. In this study we used in situ hybridization and real-time PCR to study the gene expression of monoamine transporters, such as NET, SERT, VMAT2, EMT and OCT1/2, in normal as well as in pre-eclamptic placentae. We demonstrated high expression of NET mRNA in the trophoblast cells of the anchoring villi and a lower expression intensity in the chorionic villi. SERT mRNA was mainly detected in chorionic villi. VMAT2 mRNA was not detected in the central part of the placenta but was present in the spiral arteries of placenta bed biopsies, in cytokeratin positive cells. EMT mRNA was mainly detected in the intra lobular septa and together with OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias. Moreover, quantitative analysis showed a significant lower expression of NET and EMT mRNAs in pre-eclamptic placentae as compared to the control group. A defective gene expression or function of these monoamines transporters might explain the elevated concentrations of monoamines in pre-eclamptic patients. Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus.
Bottalico
B
B
Department of Obstetrics and Gynecology, Lund University Hospital, Klinikgatan, 221 85, Lund, Scania, Sweden.
Larsson
I
I
Brodszki
J
J
Hernandez-Andrade
E
E
Casslén
B
B
Marsál
K
K
Hansson
S R
SR
D000328:Adult; D002824:Chorionic Villi / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D027702:Organic Cation Transporter 1 / Q000235:genetics; D000075102:Organic Cation Transporter 2; D010920:Placenta / Q000098:blood supply / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000235:genetics*; D014327:Trophoblasts / Q000737:chemistry; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D000099254:Organic Cation Transporter 3
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D000099254:Organic Cation Transporter 3; C493452:SLC18A2 protein, human; C491013:SLC22A2 protein, human; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human