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Maternal circulating miRNAs contribute to negative pregnancy outcomes by altering placental transcriptome and fetal vascular dynamics
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Maternal circulating miRNAs contribute to negative pregnancy outcomes by altering placental transcriptome and fetal vascular dynamics
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Journal Article
Maternal circulating miRNAs contribute to negative pregnancy outcomes by altering placental transcriptome and fetal vascular dynamics
2023
Overview
Circulating miRNAs the in blood are promising biomarkers for predicting pregnancy complications and adverse birth outcomes. Previous work identified 11 gestationally elevated maternal circulating miRNAs ( HEa miRNAs) that predicted infant growth deficits following prenatal alcohol exposure and regulated epithelial–mesenchymal transition in the placenta. Here we show that a single intravascular administration of pooled murine-conserved HEa miRNAs to pregnant mice on gestational day 10 (GD10) attenuates umbilical cord blood flow during gestation, explaining the observed intrauterine growth restriction (IUGR), specifically decreased fetal weight, and morphometric indices of cranial growth. Moreover, RNAseq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of members of the Notch pathway ( Dll4 , Rfng , Hey1 ), which is a pathway important for trophoblast migration and differentiation. Weighted gene co-expression network analysis also identified chemokine signaling, which is responsible for regulating immune cell-mediated angiogenesis in the placenta, as an important predictor of fetal growth and head size. Our data suggest that HEa miRNAs perturb the expression of placental genes relevant for angiogenesis, resulting in impaired umbilical cord blood flow and subsequently, IUGR.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
