title: The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: identification of novel molecular functions involved in this process.
abstract: OBJECTIVE
  The aim of this study was to identify changes in the cervical transcriptome in the human uterine cervix as a function of ripening before the onset of labor.
  
  
  METHODS
  Human cervical tissue was obtained from women at term not in labor with ripe (n = 11) and unripe (n = 11) cervices and profiled using Affymetrix GeneChip HGU133Plus2.0 arrays. Gene expression was analyzed using a moderated t-test (False Discovery Rate 5%). Gene ontology and pathway analysis were performed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for confirmation of selected differentially expressed genes.
  
  
  RESULTS
  (1) Ninety-one genes were differentially expressed between ripe and unripe groups. (2) Cervical ripening was associated with enrichment of specific biological processes (e.g. cell adhesion, regulation of anatomical structure), pathways and 11 molecular functions (e.g. extracelluar matrix (ECM)-structural constituent, protein binding, glycosaminoglycan binding). (3) qRT-PCR confirmed that 9 of 11 tested differentially expressed genes (determined by microarray) were upregulated in a ripe cervix (e.g. MYOCD, VCAN, THBS1, COL5A1). (4) Twenty-three additional genes related to ECM metabolism and adhesion molecules were differentially regulated (by qRT-PCR) in ripe cervices.
  
  
  CONCLUSIONS
  (1) This is the first description of the changes in the human cervical transcriptome with ripening before the onset of labor. (2) Biological processes, pathways and molecular functions were identified with the use of this unbiased approach. (3) In contrast to cervical dilation after term labor, inflammation-related genes did not emerge as differentially regulated with cervical ripening. (4) Myocardin was identified as a novel gene upregulated in human cervical ripening.
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women's Hospital, Detroit, MI 48201, USA. shassan@med.wayne.edu
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Nhan-Chang
authors.forename: Edi
authors.initials: E
authors.lastname: Vaisbuch
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
authors.forename: Pooja
authors.initials: P
authors.lastname: Mittal
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Shali
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Niels
authors.initials: N
authors.lastname: Uldbjerg
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D020070:Cervical Ripening / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002584:Cervix Uteri / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007745:Labor Onset / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D047929:Term Birth / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin