PS-B05-11: IMPAIRED CELL INTERACTIONS AT THE PRE-ECLAMPTIC MATERNAL-FOETAL INTERFACE

• DOI: 10.1097/01.hjh.0000916520.83656.b0
• Publication Date: 2023-01-12T16:02:21Z
• Authors: Olivia Nonn; Olivia Debnath; Daniela Valdes; Katja Sallinger; Ali Kerim Secener; Sandra Haider; Sebastian Tiesmeyer; Fabian Coscia; Amin El Heliebi; Basky Tilaganathan; Dominik N Mueller; Berthold Huppertz; Martin Gauster; Naveed Ishaque; Florian Herse
• Keywords: Syncytiotrophoblasts; Trophoblast; Gestational hypertension

Hypertensive disorders in pregnancy, of which the multisystem syndrome pre-eclampsia is most severe, leading to preterm delivery, maternal mortality and life-long complications1. Pre-eclampsia lacks early screening tools2,3 causal therapies4,5. To elucidate disease dynamics, we present first spatio-temporal study comparing single-nuclei transcriptomes human pre-eclamptic placentae healthy controls, contextualising this a comprehensive including late gestational implementing spatial multi-omics methods. Here show trophoblast pre-fusion cells their developmental trajectory running towards novel cell-state identify as juvenile syncytiotrophoblast. We found that disturbed development, reconstructed by dysregulation differentiation-driving transcription factor p300, likely initiates pre-eclampsia. suggest be dysregulated syncytiotrophoblast differentiation: Disease-specific premature differentiation maternal-foetal barrier leads senescent syncytiotrophoblastic interaction through circulation with vessels. This disrupted decidual response via LEP, GDF15 INHBA. Our results highlight cellular communication from foetal side during development starting maturation. provide new targets for potential prevention order protect mother child increased morbidity but also cardiovascular risk.