title: Characterization of the myometrial transcriptome in women with an arrest of dilatation during labor.
abstract: OBJECTIVE
  The molecular basis of failure to progress in labor is poorly understood. This study was undertaken to characterize the myometrial transcriptome of patients with an arrest of dilatation (AODIL).
  
  
  METHODS
  Human myometrium was prospectively collected from women in the following groups: (1) spontaneous term labor (TL; n=29) and (2) arrest of dilatation (AODIL; n=14). Gene expression was characterized using Illumina® HumanHT-12 microarrays. A moderated Student's t-test and false discovery rate adjustment were used for analysis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of selected genes was performed in an independent sample set. Pathway analysis was performed on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). The MetaCore knowledge base was also searched for pathway analysis.
  
  
  RESULTS
  (1) Forty-two differentially expressed genes were identified in women with an AODIL; (2) gene ontology analysis indicated enrichment of biological processes, which included regulation of angiogenesis, response to hypoxia, inflammatory response, and chemokine-mediated signaling pathway. Enriched molecular functions included transcription repressor activity, heat shock protein (Hsp) 90 binding, and nitric oxide synthase (NOS) activity; (3) MetaCore analysis identified immune response chemokine (C-C motif) ligand 2 (CCL2) signaling, muscle contraction regulation of endothelial nitric oxide synthase (eNOS) activity in endothelial cells, and triiodothyronine and thyroxine signaling as significantly overrepresented (false discovery rate <0.05); (4) qRT-PCR confirmed the overexpression of Nitric oxide synthase 3 (NOS3); hypoxic ischemic factor 1A (HIF1A); Chemokine (C-C motif) ligand 2 (CCL2); angiopoietin-like 4 (ANGPTL4); ADAM metallopeptidase with thrombospondin type 1, motif 9 (ADAMTS9); G protein-coupled receptor 4 (GPR4); metallothionein 1A (MT1A); MT2A; and selectin E (SELE) in an AODIL.
  
  
  CONCLUSIONS
  The myometrium of women with AODIL has a stereotypic transcriptome profile. This disorder has been associated with a pattern of gene expression involved in muscle contraction, an inflammatory response, and hypoxia. This is the first comprehensive and unbiased examination of the molecular basis of an AODIL.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Ichchha
authors.initials: I
authors.lastname: Madan
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhatti
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Moshe
authors.initials: M
authors.lastname: Mazor
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D007747:Labor Stage, First / Q000235:genetics*; D008668:Metallothionein / Q000235:genetics; D009119:Muscle Contraction / Q000235:genetics; D009215:Myometrium / Q000737:chemistry*; D019001:Nitric Oxide Synthase / Q000235:genetics; D007744:Obstetric Labor Complications / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D018932:Chemokine CCL2; D008668:Metallothionein; D019001:Nitric Oxide Synthase
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