Preterm and term cervical ripening in CD1 mice (Mus musculus): Similar or divergent molecular mechanisms?

Juan M. Gonzalez, Hua Xu, Jinghua Chai, Ella Ofori, Michal A. Elovitz

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Premature cervical ripening is believed to contribute to preterm birth (PTB). Preterm cervical ripening may be due to an aberrant regulation in timing of the same processes that occur at term, or may result from unique molecular mechanisms. Using mouse models of PTB, this study sought to investigate if the molecular mechanisms that govern cervical ripening were similar between preterm and term. Lipopolysaccharide (LPS) is infused into the uterine horn to create a mouse model of inflammation-induced PTB. For a noninfectious model of PTB, RU486 was administered. Both models result in delivery of pups in 8-24 h. Cervical tissues were collected from these models, as well as throughout gestation. Cervical tissues from E15 (preterm), E15 LPS (preterm inflammation), and E18.5 (term) were used for microarray analysis (n = 18). Additional experiments using gestational time course specimens were performed to confirm microarray results. Specific gene pathways were differentially expressed between the groups. Genes involved in immunity and inflammation were increased in the cervix in inflammation-induced PTB; term labor was not associated with differential expression of immune pathways. Cytokine expression was not increased in cervices during term labor, but was increased in the pospartum period. Epithelial cell differentiation pathway was significantly altered in term, but not preterm, labor. Activation of immune pathways may be sufficient for cervial ripening, but does not appear necessary. Differential expression of the epithelial cell differentiation pathway appears necessary in the process of cervical repair. Our results indicate that the molecular mechanisms governing preterm and term cervical ripening are distinctly different.

Original languageEnglish
Pages (from-to)1226-1232
Number of pages7
JournalBiology of Reproduction
Volume81
Issue number6
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Cervical remodeling
  • Cervical ripeing
  • Cervix
  • Parturition
  • Pregnancy
  • Preterm birth

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