Placental small-RNA sequencing reveals a distinct microRNA signature and its functional relevance in a preeclampsia rat model

OBJECTIVE: Despite extensive investigations over the last few decades, molecular mechanisms underlying the pathogenesis of preeclampsia remain incompletely understood. Emerging evidence suggests that microRNAs (miRNAs) regulate key pathological processes in preeclampsia including endothelial dysfunction, inflammation, and oxidative stress. However, a comprehensive profiling of miRNA expression has not been previously carried out. Thus, using reduced uterine perfusion pressure (RUPP) model of preeclampsia, we performed placental miRNA sequencing to identify functional relevance of abnormally expressed miRNAs. METHODS: Blood pressure was measured via carotid catheterization on gestational day (GD)19. Placental small-RNA sequencing was performed using Illumina NextSeq2000 sequencer. RESULTS: Our analysis identified 142 differentially regulated miRNAs (40 up- and 102 down-regulated) in placenta from RUPP rats. The top upregulated miRNAs included miR-211-3p, miR-628, miR-6324, miR-363-5p, and miR-6329, while miR-3587, miR-29b-3p, miR-3556a, miR-29a-3p, and miR-21-3p were the most downregulated. Functional annotation revealed associations with immune response (miR-363, miR-21, miR-29), B-cell differentiation (miR-628), T-cell activation (miR-21), adipogenesis, and lipid metabolism (miR-211, miR-29, miR-21), and angiogenesis (miR-363, miR-21). Further, gene ontology analysis revealed significant enrichment in biological processes; regulation of transport, cell-cell signaling, and calcium-dependent exocytosis, cellular components; synaptic vesicles, perinuclear cytoplasm, and clathrin-coated vesicles, and molecular functions; glycoprotein binding, protein dimerization, and myosin binding. CONCLUSION: These findings suggest that robust miRNA dysregulation in RUPP rats may underlie disease pathogenesis.