OBJECTIVE: This study aimed to discover "signature pathways" that characterize biologic processes, based on genes differentially expressed in the uterine cervix before and after spontaneous labor. STUDY DESIGN: The cervical transcriptome was characterized previously from biopsy specimens taken before and after term labor. Pathway analysis was used to study the differentially expressed genes, based on 2 gene-to-pathway annotation databases (Kyoto Encyclopedia of Genes and Genomes [Kanehisa Laboratories, Kyoto University, Kyoto, Japan] and Metacore software [GeneGo, Inc, St. Joseph, MI]). Overrepresented and highly impacted pathways and connectivity nodes were identified. RESULTS: Fifty-two pathways in the Metacore database were enriched significantly in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling. Two novel pathways were plasmin signaling and plasminogen activator urokinase signaling. The same analysis with the Kyoto Encyclopedia of Genes and Genomes database identified 4 significant pathways that the impact analysis confirmed. Multiple nodes that provide connectivity within the plasmin and plasminogen activator urokinase signaling pathways were identified. CONCLUSION: Three strategies for pathway analysis were consistent in their identification of novel, unexpected, and expected pathways, which suggests that this approach is both valid and effective for the elucidation of biologic mechanisms that are involved in cervical dilation and remodeling.