Circulating exosomal miRNA profile during term and preterm birth pregnancies - a longitudinal study

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 10 per each gestational period respectively) across gestation (i.e. first, second, third trimester and at the time of delivery). Exosomal miRNA present in maternal circulation was determined using NextSeq 500 High Output 75 cycles sequencing platform. Changes in exosomal miRNA signature in maternal plasma during term and preterm gestation. A total of 167 and 153 miRNAs were found to significantly change (p-value < 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-value < 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 analysis establish that the differences on the miRNA profile are targeting signaling pathways associated with TGF-b signaling, p53, and glucocorticoid receptor signaling, respectively. This data suggest that the miRNA content of circulating exosomes in maternal blood might represent a biomolecular "fingerprint" of the progression of pregnancy