Therapies for preeclampsia and fetal growth restriction: restoration of uterine blood flow tested in mouse models
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Abstract
Preeclampsia (PE) and fetal growth restriction (FGR) complicate over 10% of human pregnancies and contribute significantly to fetal and maternal morbidity and mortality. Although the causes of PE and FGR are not well understood, they are known to be associated with impaired uterine artery blood flow. Endothelial nitric oxide synthase knockout mice (eNOS-/-) and catechol-O-methyltransferase knockout mice (COMT-/-) exhibit many signs of PE during pregnancy and deliver growth-restricted pups. We tested the ability of two potential treatments; resveratrol and 2-methoxyestradiol (2-ME) to increase uteroplacental blood flow and therefore ameliorate signs of PE and rescue FGR in relevant mouse models. 2-ME administration led to normalization of umbilical artery blood flow velocity and proteinuria in COMT-/- mice. Resveratrol supplementation increased uterine artery blood flow velocity and pup weight in COMT-/- but not in eNOS-/- mice. Our results indicate that resveratrol and 2-ME may have therapeutic potential in cases of PE and FGR.