1: Identification of signature pathways at the site of rupture in chorionic membranes in spontaneous labor at term

Article Outline

• Objective
• Study Design
• Results
• Conclusion
• Copyright

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Objective 

The mechanisms responsible for spontaneous rupture of membranes (SROM) remain to be elucidated. This study was undertaken to examine differences in the transcriptome between the site of membrane rupture and a section of the chorionic membranes away from the site of rupture.

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Study Design 

Extra-placental membranes were prospectively collected from women who underwent a vaginal delivery after SROM at term. Membranes with histological chorioamnionitis or meconium staining were excluded. The transcriptome of individual sets (n=20) of amnion and chorion from the site of rupture and membranes distal from the site of rupture was profiled with Illumina HumanHT-12 microarrays. Selected differentially expressed genes were validated using qRT-PCR on a separate set of samples (n=10).

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Results 

1) 677 genes were differentially expressed in the chorion between the rupture and non-rupture sites (false discovery rate <0.1 and fold change >1.5); 2) qRT-PCR confirmed increased expression of IL-6 and PTGS2 and decreased expression of progestagen-associated endometrial protein (PAEP), granulysin (GNLY), CXCL12, CXCL14, IGFBP2, IGFBP4, cannabinoid receptor 1(CNR1) and ADAM metallopeptidase with thrombospondin type-1 motif-5(ADAMTS5) in the rupture site compared to the non-rupture site; 3) biological processes with enrichment included:anatomical structure development, cell adhesion, signal transduction and cell communication; 4) extracellular matrix-receptor interaction and complement and coagulation cascades were among the most impacted signaling pathways by the presence of rupture in the membranes and 5) there were no significant regional (rupture vs non-rupture) differences in the amnion transcriptome.

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Conclusion 

1) The transcriptome of fetal membranes in SROM in term labor is characterized by region and tissue-specific differential expression of genes involved in signal transduction, cell communication, graft-versus-host disease and the complement and coagulation cascades; 2) these differences were detected in the chorion but not in the amnion, and confirmed by qRT-PCR.