Project description: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.
Project description:The first trimester is a critical window of maternal-fetal communication for pregnancy. RNA-sequencing of matched maternal decidua (4) and placenta (4) identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface, 32 in females and 59 in males.
Project description:Maternal and fetal monocytes and tissue macrophages (decidual macrophages, Hofbauer cells) at the feto-maternal interface have different methylome.
Project description:Maternal and fetal monocytes and tissue macrophages (decidual macrophages, Hofbauer cells) at the feto-maternal interface have different methylome. Paired and balanced design. We compared maternal blood monocytes (MB) vs. cord blood monocytes (CB), maternal blood monocytes (MB) vs. decidual macrophages (Deci), cord blood monocytes (CB) vs placental macrophages (villi) and decidual macrophages (Deci) vs. placental macrophages (villi).
Project description:The first trimester is a critical window of maternal-fetal communication for pregnancy. Using single cell RNA-sequencing to dissect placenta heterogeneity, we identified five major cell types (trophoblasts, stromal cells, hofbauer cells, antigen presenting cells and endothelial cells). We identified seven unique trophoblast subclusters, including new subtypes that transition into the terminal cell types, extra-villous trophoblasts and syncytiotrophoblasts. As fetal sex impacts pregnancy, we analyzed sex differences in each cell type and identified differences in immune cell function. TGFβ1, β-estradiol, and dihydrotestosterone emerge as upstream regulators of sexually dimorphic genes in a cell type specific manner. Thus, the fetal contribution at the maternal-fetal interface is cell and sex specific.
Project description:The involvement of epigenetic regulation of cis-regulatory elements and retrotransposons in the maternal-fetal interface of COVID-19-related pregnancy complications.