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. Study Design. Human cervical tissue was obtained from women at term not in labor with ripe (n ¼ 11) and unripe (n ¼ 11) cervices and profiled using Affymetrix GeneChip 1 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. Conclusion.(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.

Cervical Remodeling/Ripening at Term and Preterm Delivery: The Same Mechanism Initiated by Different Mediators and Different Effector Cells

“…A human study emphasizes the lack of correlation between inflammation and cervical remodeling at term. In this study, the authors reported that inflammation-related genes did not emerge as differentially express with cervical ripening [20]. Even though several studies in animals suggest that inflammatory cells do not participate in cervical ripening at term, some human studies suggest that inflammatory cells do participate in the cervical changes in term parturition [21], [22].…”

Transcriptome interrogation of human myometrium identifies differentially expressed sense-antisense pairs of protein-coding and long non-coding RNA genes in spontaneous labor at term

“…There is compelling evidence that physiologic parturition is associated with cellular and molecular signatures of inflammation in the chorioamniotic membranes [28,91–96], myometrium [18,20,22,23,25–27,30,93,96–102], and cervix [19,21,24,93,96,103–107]. Indeed, the participation of chemokines and pro-inflammatory cytokines [108–126], eicosanoids [99,127–137] and lipooxygenase arachidonate products [138–140] in physiologic labor is well established.…”

A molecular signature of an arrest of descent in human parturition

“…Studies using transcriptomics have demonstrated that uncomplicated spontaneous term labor is characterized by the overexpression of genes involved in the inflammatory response in the chorioamniontic membranes115;116, the uterine cervix69;117;118, and the myometrium,77;97;98;100;119 thereby implicating inflammation as a component of the common pathway of parturition.…”