Expression of AT1R, AT2R and AT4R and Their Roles in Extravillous Trophoblast Invasion in the Human

The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. An...

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Published in:Placenta (Eastbourne) Vol. 31; no. 5; pp. 448 - 455
Main Authors: Williams, P.J., Mistry, H.D., Innes, B.A., Bulmer, J.N., Broughton Pipkin, F.
Format: Journal Article
Language:English
Published: Kidlington Elsevier Ltd 01.05.2010
Elsevier
Subjects:
Abortion, Legal
Adult
Angiotensin
Angiotensins - pharmacology
Biological and medical sciences
Biomarkers - metabolism
Cell Movement - drug effects
Embryology: invertebrates and vertebrates. Teratology
Female
Fundamental and applied biological sciences. Psychology
Gene Expression
Gestational Age
Humans
Internal Medicine
NADPH Oxidases - metabolism
Obstetrics and Gynecology
Organ Culture Techniques
Placenta
Placentation - physiology
Pre-Eclampsia - metabolism
Pregnancy
Receptor
Receptor, Angiotensin, Type 1 - genetics
Receptor, Angiotensin, Type 1 - metabolism
Receptor, Angiotensin, Type 2 - genetics
Receptor, Angiotensin, Type 2 - metabolism
Receptors, Angiotensin - genetics
Receptors, Angiotensin - metabolism
RNA, Messenger - metabolism
Term Birth
Trophoblasts - drug effects
Trophoblasts - metabolism
Type 1
Type 2
Xanthine Oxidase - metabolism
Type 2
Placenta
Receptor
Angiotensin
Type 1
Human
Trophoblaste
Vertebrata
Mammalia
Fetal membrane
Invasion
ISSN:0143-4004, 1532-3102, 1532-3102
Online Access:Get full text
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Summary:The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. Angiotensin (3-8) (AngIV) has a specific receptor (AT4R) and evokes hypertrophy, vasodilatation and vascular inflammatory response. The aim of this study was to characterise placental expression of AT1R, AT2R and AT4R, and to determine whether AngII and AngIV regulate extravillous trophoblast (EVT) invasion, apoptosis and proliferation. Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 8–10 weeks gestation (early TOP), 12–14 weeks gestation (mid TOP) or at delivery following normal pregnancy or with pre-eclampsia (PE). Immunohistochemistry and qRT-PCR were performed to determine placental mRNA and protein expression of AT1R, AT2R and AT4R at all gestational ages. EVT invasion following culture with AngII or AngIV was assessed in early placental tissue using Matrigel invasion assays. Invasion was assessed on day 6 of culture and placental explants were harvested for immunohistochemical analysis of apoptosis and proliferation. The results from qRT-PCR and immunohistochemistry showed placental AT1R expression which did not vary with gestation. The highest levels of expression of AT2R were found in early and mid TOP placentae compared to term pregnancy. Expression of AT4R was increased in term placentae, with a significant reduction in PE placentae. Moreover, culture with AngIV or AngII increased EVT invasion from placental explants, which showed increased trophoblast proliferation and reduced apoptosis. This study has characterised expression of AT4R and AT1R and AT2R in human placenta throughout normal pregnancy and in PE. Both AngIV and AngII may play an important role in normal pregnancy.
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ISSN:0143-4004
1532-3102
1532-3102
DOI:10.1016/j.placenta.2010.02.014