A Cross-Sectional Analysis of Syncytiotrophoblast Membrane Extracellular Vesicles Derived Transcriptomic Biomarkers in Preeclampsia

Background Preeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2-8% of pregnancies worldwide. Biomarker(s) for PE exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles - STB-EVs-have been identified as being involved in PE with the potential to act as liquid biopsies. Objective To identify differences in STB-EV and placenta transcriptome between PE and normal pregnancy (NP). Methods We performed RNA-sequencing (RNA-seq) on placental tissue, medium/large and small STB-EVs from PE (n=6) and NP (n=6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions. Results Our analysis identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in-silico prediction of STB-EV-based mechanistic pathways. Conclusions In this study, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies. Funding This research was funded by the Medical Research Council (MRC Programme Grant (MR/J0033601) and the Medical & Life Sciences translational fund (BRR00142 HE01.01)