Placental Exosomes as Early Biomarker of Preeclampsia: Potential Role of Exosomal MicroRNAs Across Gestation

TLDR

Early prediction of preeclampsia is essential to reduce its prevalence and severity. This study examined whether circulating exosomes and their microRNA cargo could serve as an early biomarker for preeclampsia. A retrospective stratified study quantified total and placenta‑derived exosomes in maternal plasma of normal and preeclamptic pregnancies using nanoparticle tracking analysis and Illumina TruSeq small‑RNA library preparation. Presymptomatic preeclamptic women had significantly higher total and placenta‑derived exosome concentrations throughout pregnancy, with AUCs of 0.745 and 0.829, and over 300 miRNAs—including hsa‑miR‑486‑1‑5p and hsa‑miR‑486‑2‑5p—were identified, indicating diagnostic potential.

Abstract

Abstract Context There is a need to develop strategies for early prediction of patients who will develop preeclampsia (PE) to establish preventive strategies to reduce the prevalence and severity of the disease and their associated complications. Objective The objective of this study was to investigate whether exosomes and their microRNA cargo present in maternal circulation can be used as early biomarker for PE. Design, Setting, Patients, and Interventions A retrospective stratified study design was used to quantify total exosomes and placenta-derived exosomes present in maternal plasma of normal (n = 32 per time point) and PE (n = 15 per time point) pregnancies. Exosomes present in maternal circulation were determined by nanoparticle tracking analysis. An Illumina TruSeq® Small RNA Library Prep Kit was used to construct a small RNA library from exosomal RNA obtained from plasma samples. Results In presymptomatic women, who subsequently developed PE, the concentration of total exosomes and placenta-derived exosomes in maternal plasma was significantly greater than those observed in controls, throughout pregnancy. The area under the receiver operating characteristic curves for total exosome and placenta-derived exosome concentrations were 0.745 ± 0.094 and 0.829 ± 0.077, respectively. In total, over 300 microRNAs were identified in exosomes across gestation, where hsa-miR-486-1-5p and hsa-miR-486-2-5p were identified as the candidate microRNAs. Conclusions Although the role of exosomes during PE remains to be fully elucidated, we suggest that the concentration and content of exosomes may be of diagnostic utility for women at risk for developing PE.