title: Transcriptional profiling with a pathway-oriented analysis in the placental villi of unexplained miscarriage.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Systemic vulnerability for ROS in PV could be a major cause of unexplained miscarriage.
authors.affiliation: Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Lyu
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.forename: J A
authors.initials: JA
authors.lastname: Yoon
authors.forename: Mi-Uk
authors.initials: MU
authors.lastname: Chin
authors.forename: S R
authors.initials: SR
authors.lastname: Sung
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: W S
authors.initials: WS
authors.lastname: Lee
authors.forename: T K
authors.initials: TK
authors.lastname: Yoon
authors.forename: D H
authors.initials: DH
authors.lastname: Cha
authors.forename: S H
authors.initials: SH
authors.lastname: Shim
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D002824:Chorionic Villi / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005978:Glutathione