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Global Gene Expression Analysis of Term Amniotic Fluid Cell-Free Fetal RNA

Hui, Lisa MBBS; Wick, Heather C. BSc; Edlow, Andrea G. MD; Cowan, Janet M. PhD; Bianchi, Diana W. MD

doi: 10.1097/AOG.0b013e318293d70b
Original Research

OBJECTIVE: To identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants.

METHODS: This was a prospective whole genome microarray study comparing eight amniotic fluid samples collected from women at term who underwent prelabor cesarean delivery and eight second-trimester amniotic fluid samples from routine amniocenteses. A functional annotation tool was used to compare tissue expression patterns in term and second-trimester samples. Pathways analysis software identified physiologic systems, molecular and cellular functions, and upstream regulators that were significantly overrepresented in term amniotic fluid.

RESULTS: There were 2,871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid.

CONCLUSIONS: Transcriptomic analysis of amniotic fluid cell-free fetal RNA detects fetal maturation processes activated in term pregnancy. These findings further develop the concept of amniotic fluid supernatant as a real-time gene expression “summary fluid” and support its potential for future studies of fetal development.


Supplemental Digital Content is Available in the Text.Global gene expression analysis of term amniotic fluid reveals upregulation of multiple biological pathways involved in fetal maturation and preparation for labor.

Discipline of Obstetrics, Gynaecology and Neonatology, Sydney Medical School, University of Sydney, Sydney, Australia; the Mother Infant Research Institute and the Cytogenetics Laboratory, Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts; and the Department of Computer Science, Tufts University, Medford, Massachusetts.

Corresponding author: Lisa Hui, MBBS, 96 Ivanhoe Parade, Ivanhoe VIC 3079 Australia; e-mail:

Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01 HD42053-09 and R01 HD058880; the University of Sydney Medical School (Albert S. McKern Research Scholarship to Dr Hui); and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (Fotheringham Fellowship to Dr Hui).

Financial Disclosure The authors did not report any potential conflicts of interest.

Presented at the 33rd Annual Meeting of the Society for Maternal-Fetal Medicine, February14–16, 2013, San Francisco, California.

The authors thank the staff of the Labor and Delivery Unit at Tufts Medical Center for assistance with patient recruitment and sample collection; and Karen Krajewski from the Department of Pathology and Laboratory Medicine at Tufts Medical Center for assistance with control amniotic fluid samples and data collection.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.