title: Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.
abstract: BACKGROUND
  Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP.
  
  
  METHODS
  Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining.
  
  
  RESULTS
  The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas.
  
  
  CONCLUSIONS
  Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.
authors.forename: QiaoLing
authors.initials: Q
authors.lastname: Du
authors.forename: YouDong
authors.initials: Y
authors.lastname: Pan
authors.forename: YouHua
authors.initials: Y
authors.lastname: Zhang
authors.forename: HaiLong
authors.initials: H
authors.lastname: Zhang
authors.forename: YaJuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: JunLei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China. tduan@yahoo.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
authors.forename: JianFeng
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000150:complications; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001647:Bile Acids and Salts