title: Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother-placenta-foetus trio during cholestasis of pregnancy.
abstract: OBJECTIVE
  Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio.
  
  
  METHODS
  Using HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence.
  
  
  RESULTS
  In ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2.
  
  
  CONCLUSIONS
  UDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP.
authors.affiliation: Ramón Sardá Mother' and Children's Hospital, Buenos Aires, Argentina.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Estiú
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Monte
authors.forename: Laura
authors.initials: L
authors.lastname: Rivas
authors.forename: Maria
authors.initials: M
authors.lastname: Moirón
authors.forename: Laura
authors.initials: L
authors.lastname: Gomez-Rodriguez
authors.forename: Tomas
authors.initials: T
authors.lastname: Rodriguez-Bravo
authors.forename: Jose J G
authors.initials: JJ
authors.lastname: Marin
authors.forename: Rocio I R
authors.initials: RI
authors.lastname: Macias
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000503:physiopathology; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods; D015854:Up-Regulation; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011374:Progesterone; D014580:Ursodeoxycholic Acid
keywords: bile acids; cholestasis of pregnancy; progesterone; ursodeoxycholic acid
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