title: Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term.
abstract: to characterize the transcriptome of human myometrium during spontaneous labor at term.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA. pmittal@med.wayne.edu
authors.forename: Pooja
authors.initials: P
authors.lastname: Mittal
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Nhan-Chang
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Stephen
authors.initials: S
authors.lastname: Lye
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.forename: Shali
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007743:Labor, Obstetric / Q000235:genetics / Q000502:physiology*; D009215:Myometrium / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D012313:RNA