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

• Published in: Endocrinology (Philadelphia) Vol. 160; no. 2; pp. 249 - 275
• Main Authors: Menon, Ramkumar, Debnath, Chirantan, Lai, Andrew, Guanzon, Dominic, Bhatnagar, Shinjini, Kshetrapal, Pallavi K, Sheller-Miller, Samantha, Salomon, Carlos
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.02.2019; Oxford University Press
• Subjects: Bioinformatics; Birth; Blood circulation; Bone morphogenetic proteins; Case-Control Studies; Computational biology; Correlation analysis; Endocrinology; Exosomes; Exosomes - metabolism; Female; Gene Expression Profiling; Genetic aspects; Gestation; Gestational Age; Glucocorticoids; Human reproduction; Humans; Longitudinal Studies; MicroRNA; MicroRNAs - metabolism; miRNA; Neonates; Newborn infants; Obstetrical research; Organelles; p53 Protein; Parturition; Physiological aspects; Pregnancy; Pregnancy - metabolism; Pregnant women; Premature birth; Premature Birth - metabolism; Premature infants; Signaling; Term Birth - metabolism; Time; Transforming growth factors; Tumor proteins; Young Adult; India
• ISSN: 1945-7170; 0013-7227; 1945-7170
• DOI: 10.1210/en.2018-00836

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.