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

Pooja Mittal*, Roberto Romero, Adi L. Tarca, Juan Gonzalez, Sorin Draghici, Yi Xu, Zhong Dong, Chia Ling Nhan-Chang, Tinnakorn Chaiworapongsa, Stephen Lye, Juan Pedro Kusanovic, Leonard Lipovich, Shali Mazaki-Tovi, Sonia S. Hassan, Sam Mesiano, Chong Jai Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 f-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.

Original languageEnglish
Pages (from-to)617-643
Number of pages27
JournalJournal of Perinatal Medicine
Volume38
Issue number6
DOIs
StatePublished - Nov 2010
Externally publishedYes

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 (LIL-RA5/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

Fingerprint

Dive into the research topics of 'Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term'. Together they form a unique fingerprint.

Cite this