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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Proteomics and bioinformatics analysis reveal underlying pathways of infection associated histologic chorioamnionitis
V Tambor1, M Kacerovsky, J Lenco
1Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, Czech Republic.
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.
Insights
Microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in preterm prelabor rupture of membranes (pPROM) pregnancies are linked to poor neonatal outcomes. Proteomics identified key inflammatory proteins and oxidative stress biomarkers associated with these conditions.
Area of Science:
- Obstetrics and Gynecology
- Neonatology
- Proteomics
- Bioinformatics
Background:
- Microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) are linked to adverse neonatal outcomes in preterm prelabor rupture of membranes (pPROM).
- Identifying reliable biomarkers for MIAC and HCA in pPROM is crucial for improving neonatal care.
Purpose of the Study:
- To identify novel biomarkers and their biofunctions in pPROM pregnancies with and without MIAC and HCA.
- To elucidate the molecular pathways underlying adverse outcomes in complicated pPROM.
Main Methods:
- Quantitative shotgun proteomics was performed on amniotic fluid samples from 38 women with pPROM (19 with MIAC/HCA, 19 without).
- Ingenuity pathway analysis was employed to identify molecular networks and altered proteins.
- Gestational ages at sampling were matched between the groups.
Main Results:
- Proteomic analysis revealed significant alterations in proteins associated with immunological disease and inflammatory response in pPROM with MIAC and HCA.
- Up-regulated proteins included histones (H3, H4, H2B), cathelicidin antimicrobial peptide, myeloperoxidase, and neutrophil gelatinase-associated lipocalin.
- Biomarkers of oxidative stress and reactive oxygen species generation were identified.
Conclusions:
- Bioinformatic analysis of proteomics data successfully projected the biomolecular pathology in pPROM complicated by MIAC and HCA.
- Inflammation in this context involves oxidative-stress-associated DNA damage and proteolysis.
- The identified proteins and pathways offer potential targets for diagnostic and therapeutic strategies.
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