Document Detail

Transcriptional profiling with a pathway-oriented analysis in the placental villi of unexplained miscarriage.
MedLine Citation:
PMID:  23266290     Owner:  NLM     Status:  Publisher    
INTRODUCTION: Miscarriage is the most common placental-related complication of pregnancy. It has been extensively investigated to discover the underlying mechanism(s) by which miscarriage occurs, but in many cases the etiology still remains unclear. The aim of this study was to analyze genome-wide expression profiles of placental villi (PV) from unexplained miscarriage with a pathway-oriented method for identifying underlying mechanism(s) of unexplained miscarriage. METHODS: We investigated PV of 18 women with unexplained miscarriage and 11 women underwent normal pregnancy. Each PV was obtained through dilatation & evacuation and chorionic villous sampling, respectively. Genome-wide expression profiles of PV were analyzed by Gene Set Enrichment Analysis (GSEA) to find dysregulated signaling pathways in PV of unexplained miscarriage. RESULTS: Unsupervised hierarchical clustering showed heterogeneity of expression profiles between PV of normal developing pregnancy and unexplained miscarriage. GSEA, a supervised analysis, with KEGG pathways revealed that several gene sets associated with mitochondrial function including glutathione metabolism and oxidative phosphorylation are dysregulated in PV from unexplained miscarriage. RT-PCR, real-time RT-PCR and/or immunohistochemistry reinforced that expression of genes constituting these gene sets enriched in normal pregnancy and Cu/Zn-superoxide dismutase was down-regulated in PV of unexplained miscarriage. DISCUSSION: Structural vulnerability of placental villi for reactive oxygen species (ROS), which is caused by systemic down-regulation of mitochondrial pathways involved in mitochondrial redox balance and functions, aggravates oxidative stress with increased ROS production in PV of unexplained miscarriage. CONCLUSION: Systemic vulnerability for ROS in PV could be a major cause of unexplained miscarriage.
S W Lyu; H Song; J A Yoon; Mi-Uk Chin; S R Sung; Y S Kim; W S Lee; T K Yoon; D H Cha; S H Shim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-21
Journal Detail:
Title:  Placenta     Volume:  -     ISSN:  1532-3102     ISO Abbreviation:  Placenta     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea; Laboratory of Medical Genetics, CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea.
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