Dysregulation of miRNA–mRNA expression in fetal growth restriction in a caloric restricted mouse model

Abstract

Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA–mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.