Proteomics and bioinformatics analysis reveal underlying pathways of infection associated histologic chorioamnionitis in pPROM

V. Tambor, M. Kacerovsky, J. Lenco, G. Bhat, R. Menon

    Research output: Contribution to journalArticlepeer-review

    32 Scopus citations

    Abstract

    Introduction: The presence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) is associated with adverse neonatal outcomes in pregnancies complicated by preterm prelabor rupture of membranes (pPROM). Therefore, there is an urgent need to identify new biomarkers revealing these conditions. The objective of this study is to identify possible biomarkers and their underlying biofunctions in pPROM pregnancies with and without MIAC and HCA. Methods: A total of 72 women with pPROM were recruited. Only women with both MIAC and HCA (n = 19) and all women without these complications (n = 19) having the same range of gestational ages at sampling were included in the study. Samples of amniotic fluid were obtained by transabdominal amniocentesis, processed and analyzed using quantitative shotgun proteomics. Ingenuity pathway analysis was used to identify molecular networks that involve altered proteins. Results: Network interaction identified by ingenuity pathway analysis revealed immunological disease and the inflammatory response as the top functions and disease associated with pPROM in the presence of MIAC and HCA. The proteins involved in these pathways were significantly altered between the groups with and without the presence of both MIAC and HCA. Proteins involved included histones H3, H4, H2B, cathelicidin antimicrobial peptide, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, peptidoglycan recognition protein-1 and neutrophil defensin 1, all of which were found to be up-regulated in the presence of MIAC and HCA. Conclusion: Bioinformatic analysis of proteomics data allowed us to project likely biomolecular pathology resulting in pPROM complicated by MIAC and HCA. As inflammation is not a homogeneous phenomenon, we provide evidence for oxidative-stress-associated DNA damage and biomarkers of reactive oxygen species generation as factors associated with inflammation and proteolysis.

    Original languageEnglish (US)
    Pages (from-to)155-161
    Number of pages7
    JournalPlacenta
    Volume34
    Issue number2
    DOIs
    StatePublished - Feb 2013

    Keywords

    • Amniotic fluid
    • Chorioamnionitis
    • Ingenuity pathway analysis
    • Intraamniotic infection
    • Preterm delivery
    • Proteomics

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology
    • Developmental Biology

    Fingerprint

    Dive into the research topics of 'Proteomics and bioinformatics analysis reveal underlying pathways of infection associated histologic chorioamnionitis in pPROM'. Together they form a unique fingerprint.

    Cite this