Research ArticleReproductive Biology

Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes

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Sci. Signal.  16 May 2017:
Vol. 10, Issue 479, eaam5711
DOI: 10.1126/scisignal.aam5711

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ROS against preeclampsia

Preeclampsia is the onset of high blood pressure and proteinuria that acutely develops after about 20 weeks of pregnancy, which impairs fetal growth and can result in maternal organ damage. There are few treatment options available. Oxidative stress mediated by reactive oxygen species (ROS) has been proposed to inhibit blood vessel formation (a process called angiogenesis) in the placenta, which would be expected to increase the risk of preeclampsia; however, clinical trials have found antioxidants to be ineffective in preventing preeclampsia. Nezu et al. used a mouse model of preeclampsia in which the antioxidant system Nrf2 had been genetically or pharmacologically manipulated. Unexpectedly, genetic ablation of an inhibitor of Nrf2 or treatment with an activator of Nrf2 decreased placental angiogenesis, suppressed fetal growth, and worsened maternal survival. In contrast, deficiency of Nrf2 increased placental angiogenesis and improved fetal and maternal outcomes. These results indicate that ROS are necessary for the placental angiogenesis that reduces the risk of preeclampsia, and help to explain the negative results of the clinical trials of antioxidants.