381 - Placental exosomal microRNAs as a proxy for diagnosis of abnormal placentation and fetal outcomes

Poster Number: 381
Publication Number: 381.133

Marwa Khalil, Hackensack Meridian School of Medicine, Hackensack, NJ, United States; Megan Mitchell, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United States; Jesus Alvarez-Perez, None, Hackensack, NJ, United States; Manuel Alvarez, Hackensack University Medical Center/Hackensack Meridian School of Medicine, Hackensack, NJ, United States; Abdulla Al-Khan, Hackensack University Medical Center - Hackensack Meridian School of Medicine, Hackensack, NJ, United States; Olivier Loudig, Hackensack Meridian School of Medicine, Nutley, NJ, United States

Background: Placenta accreta spectrum (PAS) pathologies have severe maternal and fetal clinical consequences if undetected. Diagnosis requires specialist expertise which is often limited to referral centers. The identification of robust PAS biomarkers would aid in both early diagnosis and referral. The miRNA content of placenta-specific exosomes found in maternal plasma have been suggested as a potential source to non-invasively monitor pregnancy abnormalities.Previously, we found  there was insufficient separation over the range of individual values  to enable direct use as a biomarker using  data  obtained from total plasma exosomes. We therefore sought to determine if placenta-specific exosomal miRNA profiles present in maternal circulation can provide a potential source of PAS biomarkers and fetal outcomes.

Objective: To determine differential plasma exosomal miRNA expression between cases of PAS and placenta previa matched controls

Design/Methods: Plasma from 16 cases of PAS  and 16 matched controls (placenta previa without accreta) was obtained shortly before delivery. miRNA was isolated from whole maternal plasma and from placental exosomes isolated from maternal plasma using our placental Alkaline Phosphatase (PLAP) exosome isolation assay (EV-CATCHER). Small-RNA next-generation sequencing (NGS) was then performed on both whole plasma and PLAP+ exosomes on an Illumina NextSeq 500 sequencer using 75-bp paired end reads.

Results: Whole plasma miRNA profiling revealed 5 differentially expressed miRNAs [miR-21 (2.3-fold), miR-191 (2.3-fold), miR-223 (2.2-fold), miR-451(-1.41-fold) and miR-486 (-1.72-fold)] between women with PAS and placenta previa whereas the isolation of PLAP+ exosomes from maternal plasma identified 40 differentially expressed miRNAs (p < 7.1e-5) in PAS. Conclusion(s):  This study provides proof-of-concept quantification that placenta-derived PLAP+ exosomes may facilitate the early identification of PAS pathologies and that early detection of miRNA profiles in PLAP+ exosomes within maternal blood may represent a future clinically useful, non-invasive test for placental dysfunction and their fetal outcomes. Some of these miRNAs were associated with fetal inflammation and development. Current efforts are ongoing towards results validation by further analyses.