Magnetic Resonance Imaging Detects Placental Hypoxia and Acidosis in Mouse Models of Perturbed Pregnancies

Gabriele Bobek,Angela Makris,William S Price,Laura Surmon,Annemarie Hennessy,Joanne M Lind,Tim Stait-Gardner,Ana Claudia Zenclussen

doi:10.1371/journal.pone.0059971

Abstract

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

Highlights

The placenta is central in the aetiology of preeclampsia, a complication of pregnancy characterised by gestational hypertension and proteinuria and a leading cause of morbidity and mortality in both mothers and infants
Endothelial dysfunction has emerged as the proximal cause for the maternal clinical symptoms, with increased levels of soluble fms-like tyrosine kinase-1 secreted by the placenta interfering with the bioavailability of vascular endothelial growth factor (VEGF) and VEGF signalling across the maternal endothelium leading to the maternal hypertensive response [2]
Pattern of T2 contrast altered in perturbed pregnancies We examined whether morphological differences could be detected by T2 mapping in the placenta of mice subjected to two experimental models of preeclampsia; namely the reduced uterine perfusion pressure (RUPP) model and the inflammatory cytokine imbalance model (TNF-a)

Summary

Introduction

The placenta is central in the aetiology of preeclampsia, a complication of pregnancy characterised by gestational hypertension and proteinuria and a leading cause of morbidity and mortality in both mothers and infants. Endothelial dysfunction has emerged as the proximal cause for the maternal clinical symptoms, with increased levels of soluble fms-like tyrosine kinase-1 (sFlt-1) secreted by the placenta interfering with the bioavailability of vascular endothelial growth factor (VEGF) and VEGF signalling across the maternal endothelium leading to the maternal hypertensive response [2]. While dynamic contrast-enhanced MRI, using injected contrast agents, has yielded estimates of mean blood flow in the placenta of animals [11] non-invasive techniques such as arterial spin labelling, diffusion imaging and measurements of T1 (spin-lattice or longitudinal) and T2 (spin-spin or transverse) relaxation times have been investigated to provide alternative safe techniques for assessing human placental structure and function [12]

Methods

Results

Conclusion