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

Authors
  • Menon, Ramkumar1
  • Debnath, Chirantan2
  • Lai, Andrew3
  • Guanzon, Dominic3
  • Bhatnagar, Shinjini2
  • Kshetrapal, Pallavi K2
  • Sheller-Miller, Samantha1
  • Salomon, Carlos3, 4
  • 1 Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas
  • 2 Translational Health Science and Technology Institute, Faridabad, Haryana, India
  • 3 Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, University of Queensland, Brisbane, Queensland, Australia
  • 4 Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
Type
Published Article
Journal
Endocrinology
Publisher
The Endocrine Society
Publication Date
Oct 24, 2018
Volume
160
Issue
2
Pages
249–275
Identifiers
DOI: 10.1210/en.2018-00836
PMID: 30358826
PMCID: PMC6394761
Source
PubMed Central
License
Unknown

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.

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