Compartmentalized profiling of amniotic fluid cytokines in women with preterm labor

Autoři: Gaurav Bhatti aff001;  Roberto Romero aff001;  Gregory Edward Rice aff008;  Wendy Fitzgerald aff009;  Percy Pacora aff001;  Nardhy Gomez-Lopez aff001;  Mahendra Kavdia aff002;  Adi L. Tarca aff001;  Leonid Margolis aff009
Působiště autorů: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Beth aff001;  Department of Biomedical Engineering, Wayne State University College of Engineering, Detroit, Michigan, United States of America aff002;  Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, United States of America aff003;  Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, United States of America aff004;  Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, United States of America aff005;  Detroit Medical Center, Detroit, Michigan, United States of America aff006;  Department of Obstetrics and Gynecology, Florida International University, Miami, Florida, United States of America aff007;  Centre for Clinical Research, University of Queensland, Herston, Queensland, Australia aff008;  Section on Intercellular Interactions, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland, United States of America aff009;  Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff010;  Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff011;  Department of Computer Science, Wayne State University College of Engineering, Detroit, Michigan, United States of America aff012
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article



Amniotic fluid cytokines have been implicated in the mechanisms of preterm labor and birth. Cytokines can be packaged within or on the surface of extracellular vesicles. The main aim of this study was to test whether the protein abundance internal to and on the surface of extracellular vesicles changes in the presence of sterile intra-amniotic inflammation and proven intra-amniotic infection in women with preterm labor as compared to the women with preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection.

Study design

Women who had an episode of preterm labor and underwent an amniocentesis for the diagnosis of intra-amniotic infection or intra-amniotic inflammation were classified into three groups: 1) preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection, 2) preterm labor with sterile intra-amniotic inflammation, and 3) preterm labor with intra-amniotic infection. The concentrations of 38 proteins were determined on the extracellular vesicle surface, within the vesicles, and in the soluble fraction of amniotic fluid.


1) Intra-amniotic inflammation, regardless of detected microbes, was associated with an increased abundance of amniotic fluid cytokines on the extracellular vesicle surface, within vesicles, and in the soluble fraction. These changes were most prominent in women with proven intra-amniotic infection. 2) Cytokine changes on the surface of extracellular vesicles were correlated with those determined in the soluble fraction; yet the magnitude of the increase was significantly different between these compartments. 3) The performance of prediction models of early preterm delivery based on measurements on the extracellular vesicle surface was equivalent to those based on the soluble fraction.


Differential packaging of amniotic fluid cytokines in extracellular vesicles during preterm labor with sterile intra-amniotic inflammation or proven intra-amniotic infection is reported herein for the first time. The current study provides insights into the biology of the intra-amniotic fluid ad may aid in the development of biomarkers for obstetrical disease.

Klíčová slova:

Amniotic fluid – Cytokines – Forecasting – Inflammation – Labor and delivery – Preterm birth – Vesicles – Preterm labor


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