- Objective The purpose of this study was to compare the transcriptome between the site of membrane rupture and the chorioamniotic membranes away from the site of rupture. Study Design The transcriptome of amnion and chorion (n = 20 each) from and distal to the site of rupture from women with spontaneous labor and vaginal delivery at term after spontaneous rupture of membranes was profiled with Illumina HumanHT-12 microarrays. Selected genes were validated with the use of quantitative reverse transcription–polymerase chain reaction. Results Six hundred seventy-seven genes were differentially expressed in the chorion between the rupture and nonrupture sites (false discovery rate <0.1; fold change >1.5). Quantitative reverse transcription–polymerase chain reaction confirmed the differential expression in 10 of 14 genes. Enriched biological processes included anatomic structure development, cell adhesion and signal transduction. Extracellular matrix–receptor interaction was the most impacted signaling pathway. Conclusion The transcriptome of fetal membranes after spontaneous rupture of membranes in term labor is characterized by region- and tissue-specific differential expression of genes that are involved in signature pathways, which include extracellular matrix–receptor interactions.