Circulating Extracellular Vesicular MicroRNA Signatures in Early Gestation Show an Association with Subsequent Clinical Features of Pre-Eclampsia

We report the differential abundance of cell free miRNAs extracted from extracellular vesicles (EV) in the peripheral blood of pregnant women with or without preeclampsia by Next Generation Sequencing. Maternal blood samples were collected form pregnant women enrolled in the study during first to very early second trimester (11–14 weeks ), mid- to late second trimester (19–22 weeks), third trimester (36 weeks) and at delivery. Extracellular vesicles were isolated from peripheral blood and total RNA was extracted using the miRNeasy Mini Kit (Qiagen, Valencia, CA) following manufacturer's instruction. miRNA libraries were prepared utilizing NEB Next Multiplex small RNA Library prep kit (NEB E7300S; New England Biolabs, Inc, Ipswich, MA, USA) and libraries were subsequently sequenced using the HiSeq-2500 platform with single-end 50bp reads (Illumina Inc.; San Diego, CA, USA). Overall design: Differential abundance of EV specific miRNAs were examined at different trimesters. Their association with miRNA targets and pathways were reviewed in the context of preeclampsia. Furthermore, an attempt was made to establish an early predictive model of preeclampsia based on the differential abundance of miRNAs in EVs.