Circulating Exosomal miRNA Profile During Term and Preterm Birth Pregnancies: A Longitudinal Study

Abstract

Despite decades of research in the field of human reproduction, the mechanisms responsible for human parturition still remain elusive. The objective of this study was to describe the changes in the exosomal miRNA concentrations circulating in the maternal plasma between mothers delivering term and preterm neonates, across gestation using a longitudinal study design. This descriptive study identifies the miRNA content in exosomes present in maternal plasma of term and preterm birth (PTB) (n = 20 and n = 10 per each gestational period, respectively) across gestation ( i.e. , first, second, and third trimesters and at the time of delivery). Changes in exosomal miRNA signature in maternal plasma during term and preterm gestation were determined using the NextSeq 500 high-output 75 cycles sequencing platform. A total of 167 and 153 miRNAs were found to significantly change ( P < 0.05) as a function of the gestational age across term and PTB pregnancies, respectively. Interestingly, a comparison analysis between the exosomal miRNA profile between term and PTB reveals a total of 173 miRNAs that significantly change ( P < 0.05) across gestation. Specific trends of changes ( i.e. , increase, decrease, and both) as a function of the gestational age were also identified. The bioinformatics analyses establish that the differences in the miRNA profile are targeting signaling pathways associated with TGF- β signaling, p53, and glucocorticoid receptor signaling, respectively. These data suggest that the miRNA content of circulating exosomes in maternal blood might represent a biomolecular “fingerprint” of the progression of pregnancy.

Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities

“…The use of miRNA array analysis has revealed that circulating miRNAs, including miR-302b, miR-548, and miR-1253, are downregulated and that miR-223 is upregulated in plasma from those with spontaneous preterm birth compared to those with normal pregnancy [61]. Moreover, high-throughput sequencing platform results suggest that the miRNA content of circulating exosomes is significantly different in pregnant women with preterm birth or spontaneous preterm labour compared to those with normal pregnancy [40,61,62]. Thus, maternal plasma circulating miRNAs or extracellular vesicle miRNAs can be used to reflect placental pathological changes and as biomarkers to predict preterm birth.…”

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

“…One such study demonstrated considerable changes in the plasma-derived exosomal-miRNA profile of human mothers that delivered pre-term compared to those that delivered at term. Increased among the pre-term exosomal miRNA populations were miRNAs involved in glucocorticoid signaling, which is often elevated before labor progression [72]. Even non-EV-derived circulating miRNAs isolated as early as the first trimester can predict pre-term birth [73,74].…”

Extracellular vesicles in normal pregnancy and pregnancy‐related diseases

“…Extracellular vesicles have been suggested as indicators of preterm birth (PTB), with an advantage of non‐invasive isolation from maternal blood and other biological fluids . In a longitudinal study, Menon et al include a cohort of patients with term birth and PTB and reveal a total of 173 miRNAs with significant changes in circulating exosomes across three gestational period by using next‐generation sequencing. The altered miRNAs can be divided into several clusters with different trends of changes over time.…”