Amongst released purinergic mediators, extracellular ATP serves as an important signaling molecule that modulates several pathological effects in the settings of thrombosis and inflammation, such as chemotaxis, inflammasome activation and platelet activation. Extracellular ATP is converted into AMP and subsequently into adenosine by the two major nucleotide-metabolizing enzymes CD39 and CD73. In this project, the hypothesis will be tested whether placental CD39 and CD73 are expressed from very early phase onwards to term of gestation, and whether they are deregulated in response to pro-inflammatory cytokines, to ischemia–reperfusion and/or increased fluidic shear stress. A protective role of CD39 and CD73 might be disturbed in pregnancy pathologies such as pre-eclampsia (PE). This global hypothesis is tested by three work packages. The first analyzes the spatial and temporal expression and enzymatic activity of CD39 and CD73 in human placenta. The second focuses on regulation of CD39 and CD73 in response to platelet-derived factors, to inflammatory cytokines, or under conditions of ischemia–reperfusion and fluidic shear stress. Furthermore, signaling pathways involved in deregulation of placental CD39 and CD73 is analyzed. Finally, the third work package will analyze placental CD39 and CD73 in pregnancies complicated by PE.