Placental Protein Release and Uptake From the Fetal Circulation in Healthy Term Pregnancies—A Human In Vivo Exploratory Study

To better understand the crosstalk between the placenta and the fetus, we aimed to identify proteins released by the placenta into the fetal circulation, as well as proteins taken up by the placenta. This study included 75 healthy term pregnancies, analyzing proteins from plasma samples collected from the umbilical artery and vein using the Somalogic 5000-plex platform. Placental protein release and uptake were determined by comparing protein abundances in the umbilical artery and vein. Additionally, transcriptomic data mapping and gene ontology enrichment analysis were conducted to assign cellular and tissue origin and functions to the proteins. After controlling for the false discovery rate, we identified 766 proteins released by the placenta into the fetal circulation and 926 proteins taken up by the placenta (q < 0.05). Among the released proteins, 70% were previously recognized as expressed in the placenta, affirming their placental origin. Conversely, the proteins taken up from the fetal circulation showed an overrepresentation of proteins specific to bone marrow, tongue, and skeletal muscle, while proteins specific to salivary glands, liver, and placenta were underrepresented. Enrichment analysis revealed molecular functions and biological processes that promote tissue growth and differentiation. Our findings demonstrate a considerable interaction between the placenta and fetus in healthy term pregnancies, with a high number of proteins being exchanged. This research enhances our understanding of the fetal-placental interactions, paving the way for new insights into pathophysiological processes and potential therapeutic strategies in utero.