Abstract
Preeclampsia (PE) is a serious pregnancy complication that manifests as hypertension and proteinuria after the 20th gestation week. Previously, fetal hemoglobin (HbF) has been identified as a plausible causative factor. Cell-free Hb and its degradation products are known to cause oxidative stress and tissue damage, typical of the PE placenta. A1M (α1-microglobulin) is an endogenous scavenger of radicals and heme. Here, the usefulness of A1M as a treatment for PE is investigated in the pregnant ewe PE model, in which starvation induces PE symptoms via hemolysis. Eleven ewes, in late pregnancy, were starved for 36 hours and then treated with A1M (n = 5) or placebo (n = 6) injections. After injections, the ewes were re-fed and observed for additional 72 hours. They were monitored for blood pressure, proteinuria, blood cell distribution and clinical and inflammation markers in plasma. Before termination, the utero-placental circulation was analyzed with Doppler velocimetry and the kidney glomerular function was analyzed by Ficoll sieving. At termination, blood, kidney and placenta samples were collected and analyzed for changes in gene expression and tissue structure. The starvation resulted in increased amounts of the hemolysis marker bilirubin in the blood, structural damages to the placenta and kidneys and an increased glomerular sieving coefficient indicating a defect filtration barrier. Treatment with A1M ameliorated these changes without signs of side-effects. In conclusion, A1M displayed positive therapeutic effects in the ewe starvation PE model, and was well tolerated. Therefore, we suggest A1M as a plausible treatment for PE in humans.
Highlights
Preeclampsia (PE) affects up to 3–8% of pregnancies, causing a significant number of maternal and fetal deaths worldwide
Preeclampsia (PE) is a serious pregnancy complication that manifests as hypertension and proteinuria after the 20th gestation week
The ewes were re-fed and observed for additional 72 hours. They were monitored for blood pressure, proteinuria, blood cell distribution and clinical and inflammation markers in plasma
Summary
Preeclampsia (PE) affects up to 3–8% of pregnancies, causing a significant number of maternal and fetal deaths worldwide. The first stage is characterized by a defective formation of the placenta with reduced utero-placental blood flow as a consequence. This leads to oxidative stress that further aggravates the placental vascular dysfunction [2,3] and gives rise to vascular inflammation and insufficient blood perfusion of the placenta and maternal organs [4,5]. Angiospasm in the brain and brain edema may cause severe epileptic seizures–eclampsia [6]. The only cure is delivery of the fetus and removal of the placenta. As placenta removal is crucial for symptom resolution, a placental derived factor has been suggested as a culprit [1]
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