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Journal of Perinatal Medicine

Official Journal of the World Association of Perinatal Medicine

Editor-in-Chief: Dudenhausen, Joachim W.

Editorial Board Member: / Bancalari, Eduardo / Milner, Anne / Genc, Mehmet R. / Chervenak, Frank A. / Chappelle, Joseph / Bergmann, Renate L. / Bernardes, J.F. / Bevilacqua, G. / Blickstein, Isaac / Cabero Roura, Luis / Carbonell-Estrany, Xavier / Carrera, Jose M. / D`Addario, Vincenzo / D'Alton, MD, Mary E. / Dimitrou, G. / Grunebaum, Amos / Hentschel, Roland / Köpcke, W. / Kawabata, Ichiro / Keirse, Marc J.N.C. / Kurjak M.D., Asim / Lee, Ben H. / Levene, Malcolm / Lockwood, Charles J. / Marsal, Karel / Makatsariya, Alexander / Nishida, Hiroshi / Ogata, Edward / Papp, Zoltán / Pejaver, Ranjan Kumar / Pooh, Ritsuko K. / Romero, Roberto / Saugstad, Ola D. / Schenker, Joseph G. / Sen, Cihat / Seri, Istvan / Vetter, Klaus / Winn, Hung N. / Young, Bruce K. / Zimmermann, Roland

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1619-3997
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Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

Pooja Mittal
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Roberto Romero
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
  • Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Adi L. Tarca
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA
  • Department of Computer Science, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Juan Gonzalez
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Sorin Draghici
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Computer Science, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Yi Xu
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
/ Zhong Dong
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
/ Chia-Ling Nhan-Chang
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Tinnakorn Chaiworapongsa
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Stephen Lye
  • Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
/ Juan Pedro Kusanovic
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Leonard Lipovich
  • Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA
  • Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Shali Mazaki-Tovi
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Sonia S. Hassan
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
/ Sam Mesiano
  • Department of Reproductive Biology, Case Western Reserve University, Cleveland, Ohio, USA
/ Chong Jai Kim
  • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, and Detroit, Michigan, USA
  • Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA
Published Online: 2010-07-14 | DOI: https://doi.org/10.1515/jpm.2010.097

Abstract

Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term.

Methods: Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina® HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set.

Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group.

Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.

Keywords: Aldehyde dehydrogenase (ALDH2); chemokine C-C motif ligand 2 (CCL2/MCP-1); chemokine C-X-C motif ligand 6 (CXCL6/GCP2); FK506 binding-protein 5 (FKBP5); heparin binding EGF-like growth factor (HBEGF); inflammasome; inflammation; interleukin (IL)-6, -8; leukocyte immunoglobulin-like receptor, subfamily A, member 5 (LILRA5/LIR9); microarray; nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta (NFKBIZ); parturition; pregnancy; progesterone; prostaglandin-endoperoxide synthase-2 (PTGS2/COX2); suppressor of cytokine signaling 3 (SOCS3); systems biology

Corresponding authors: Pooja Mittal, MD and Roberto Romero, MD Perinatology Research Branch NICHD, NIH, DHHS Wayne State University/Hutzel Women's Hospital 3990 John R Box #4 Detroit MI 48201 USA Tel.: +1 313 993-2700 Fax: +1 313 993-2694 ;


Received: 2010-03-21

Revised: 2010-05-13

Accepted: 2010-05-18

Published Online: 2010-07-14

Published Online: 2010-07-14

Published in Print: 2010-11-01


Citation Information: Journal of Perinatal Medicine. Volume 38, Issue 6, Pages 617–643, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: https://doi.org/10.1515/jpm.2010.097, July 2010

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