AMPK: Accumulating Evidence in Support of its role in Dual Regulation of Vascular Function and Metabolism During Human Pregnancy

Adenosine monophosphate-activated protein kinase (AMPK) serves to match perfusion with metabolism. Since pregnancy necessitates significant changes in both perfusion and metabolism for supporting fetal growth, surprising is that AMPK has received scant attention during pregnancy, perhaps due to the complexity of its actions and multiple maternal, placental, and fetal targets. Here we review human as well as experimental animal studies documenting AMPK activation's broad-ranging maternal effects. Emphasized are those affecting vascular control and blood flow to the uteroplacental circulation under conditions of chronic hypoxia. Time and dosage-dependent effects on the placenta and the fetus are also reviewed, revealing that AMPK activation affects all three—maternal, placental, and fetal—pregnancy compartments. We point to the need for an integrated study of AMPK's effects in each compartment during normal as well as fetal growth-restricted (FGR) pregnancies. Since there are currently no therapies for FGR apart from early delivery, whereas there are drugs or nutritional substances activating AMPK approved for human use, such agents may represent new treatments. However, understanding their molecular mechanisms and specific actions in pregnancy compartments is required before conducting such trials.