Spatially resolved fetal and maternal cell contributions to severe Preeclampsia

The molecular and cellular pathophysiology of the fetal-maternal interface in preeclamsia remains poorly understood, but it is increasingly clear that both fetus and mother make independent contributions to it. Here, we spatially distinguish them from each other and from gestational age for the severe form of the disease, interrogating tissues and cell types beyond the placenta for the Early and Late presentation of the condition. 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 chorioamniotic 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 beneficial due to its severity. Thus, timely intervention during gestation could change the extremely poor prognosis of severe disease.