Impaired cell interactions at the pre-eclamptic maternal-fetal interface

Hypertensive disorders in pregnancy, of which the multisystem pathology pre-eclampsia is most severe, often lead to preterm delivery, maternal mortality and life-long complications. Pre-eclampsia lacks early screening tools and causal therapies, illustrating the urgent need for a better understanding of early disease dynamics. Here, we present the first study comparing single-nuclei transcriptomes of human diseased preterm preeclamptic placentae and healthy controls, embedding the characterization of the maternal-fetal barrier dysfunction in the context of a comprehensive spatio-temporal study including early and late gestational placentae. Our results highlight and contextualize a perturbed communication from fetal to maternal side during the development of pre-eclampsia starting with a dysregulated trophoblast stem-cell maturation. We provide new targets for potential early disease prevention in order to protect mother and child from increased gestational mortality and morbidity but also from life-long increased cardiovascular disease risk.