Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A2A Receptor

von Versen-Höynck, F.; Rajakumar, A.; Bainbridge, S.A.; Gallaher, M.J.; Roberts, J.M.; Powers, R.W.

doi:10.1016/j.placenta.2009.02.004

« Previous Next »Placenta
Volume 30, Issue 5 , Pages 434-442, May 2009

Human Placental Adenosine Receptor Expression is Elevated in Preeclampsia and Hypoxia Increases Expression of the A_2A Receptor

F. von Versen-Höynck
- Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Biology, University of Pittsburgh, Pittsburgh, PA, USA
- Hannover Medical School, Hannover, Germany.
A. Rajakumar
- Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Biology, University of Pittsburgh, Pittsburgh, PA, USA
S.A. Bainbridge
- Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Biology, University of Pittsburgh, Pittsburgh, PA, USA
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
M.J. Gallaher
- Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
J.M. Roberts
- Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Biology, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
R.W. Powers
- Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Biology, University of Pittsburgh, Pittsburgh, PA, USA
- Corresponding author at: Department of Obstetrics & Gynecology and Reproductive Biology, University of Pittsburgh, School of Medicine, Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA. Tel.: +1 412 641 6005; fax: +1 412 641 1503.

Accepted 23 February 2009. published online 20 March 2009.

Abstract

Placental hypoxia as a result of impaired trophoblast invasion is suggested to be involved in the pathophysiology of preeclampsia. Hypoxia is a potent stimulus for the release of adenosine, and the actions of adenosine are mediated through four adenosine receptors, A₁, A_2A, A_2B and A₃. We investigated the presence, distribution and expression of adenosine receptor subtypes in the human placenta, the expression of the adenosine receptors in placentas from pregnancies complicated by preeclampsia, small for gestational age (SGA) infants and uncomplicated pregnancies, and the effect of hypoxia on placental adenosine receptor expression. Immunofluorescent microscopy localized A₁, A_2A, A_2B and A₃ adenosine receptors to the syncytiotrophoblast, endothelial cells and myofibroblasts within the human placenta. Adenosine receptor protein and message expression levels were significantly higher in placentas from preeclamptic pregnancies with or without SGA infants, but not different in pregnancies with SGA infants alone. In vitro exposure of placental villous explants to hypoxia (2% oxygen) increased the expression of A_2A adenosine receptor 50%. These data indicate that all four known adenosine receptors are expressed in the human placenta and adenosine receptor expression is significantly higher in pregnancies complicated by preeclampsia. These data are consistent with the hypothesis that differences in placental adenosine receptors may contribute to alterations in placental function in preeclampsia.