The direct and sustained consequences of severe placental hypoxia on vascular contractility

PLoS One. 2018 Aug 24;13(8):e0202648. doi: 10.1371/journal.pone.0202648. eCollection 2018.


Introduction: Preeclampsia is a major health problem in human pregnancy, severely complicating 5-8% of all pregnancies. The emerging molecular mechanism is that conditions like hypoxic stress trigger the release of placental messengers into the maternal circulation, which causes preeclampsia. Our objective was to develop an in vitro model, which can be used to further elucidate the molecular mechanisms of preeclampsia and which might be used to find a remedy.

Methods: Human non-complicated term placentas were collected. Placental explants were subjected to severe hypoxia and the conditioned media were added to chorionic arteries that were mounted into a myograph. Contractile responses of the conditioned media were determined, as well as effects on thromboxane-A2 (U46619) induced contractility. To identify the vasoactive compounds present in the conditioned media, specific receptor antagonists were evaluated.

Results: Factors released by placental explants generated under severe hypoxia induced an increased vasoconstriction and vascular contractility to thromboxane-A2. It was found that agonists for the angiotensin-I and endothelin-1 receptor released by placental tissue under severe hypoxia provoke vasoconstriction. The dietary antioxidant quercetin could partially prevent the acute and sustained vascular effects in a concentration-dependent manner.

Discussion: Both the acute vasoconstriction, as well as the increased contractility to U46619 are in line with the clinical vascular complications observed in preeclampsia. Data obtained with quercetin supports that our model opens avenues for e.g. nutritional interventions aimed at treating or preventing preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / genetics
  • Chorion / blood supply
  • Chorion / metabolism
  • Chorion / pathology
  • Constriction, Pathologic / genetics*
  • Constriction, Pathologic / physiopathology
  • Culture Media, Conditioned / pharmacology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Hypoxia / genetics
  • Hypoxia / pathology
  • Muscle Contraction / drug effects
  • Myography
  • Placenta / metabolism*
  • Placenta / pathology
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Vasoconstriction / drug effects
  • Vasoconstriction / genetics*
  • Vasoconstrictor Agents / pharmacology


  • Culture Media, Conditioned
  • Vasoconstrictor Agents
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid

Grants and funding

This study was funded by the internal source: “Nutrim Graduate Programme” and supported by the external source: “Fonds gezond geboren” (PV). There was no additional external funding received for this study.