Characterization of the myometrial transcriptome in women with an arrest of dilatation during labor.
J Perinat Med
; 41(6): 665-81, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23893668
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). STUDYDESIGN:
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.CONCLUSION:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Primeira Fase do Trabalho de Parto
/
Perfilação da Expressão Gênica
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Complicações do Trabalho de Parto
/
Miométrio
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Pregnancy
Idioma:
En
Revista:
J Perinat Med
Ano de publicação:
2013
Tipo de documento:
Article