Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

Abstract

Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term.

Methods: Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina^® HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set.

Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group.

Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.