Spatially resolved maternal and fetal cell contributions to severe Preeclampsia

The molecular and cellular pathophysiology of the maternal-fetal interface in preeclamsia remains poorly understood, but it is increasingly clear that both mother and fetus make independent contributions to it. Here, we spatially distinguish these contributions to the severe form of the disease, per tissue and cell type, in its Early and Late presentations in gestation. In addition to concerted hypoxia, angiogenic imbalance, fibrosis and aberrant metabolism in the placenta, new maternal immune signatures, including changes in macrophages, mitochondrial dysfunction and interferon signalling in the placenta, myometrium or choreamniotic membranes, offer an explanation to systemic inflammation and endothelial dysfunction in the mother. These tissue and cell-specific responses are potential targets for therapy, with their prompt consideration in Early gestational disease likely most beneficial.