title: Placental ABCA1 and ABCG1 expression in gestational disease: Pre-eclampsia affects ABCA1 levels in syncytiotrophoblasts.
abstract: BACKGROUND
  Transplacental feto-maternal lipid exchange through the ATP-binding cassette transporters ABCA1 and ABCG1 is important for normal fetal development. However, only scarce and conflicting data exist on the involvement of these transporters in gestational disease.
  
  
  METHODS
  Placenta samples (n = 72) derived from common gestational diseases, including pre-eclampsia (PE), HELLP, intrauterine growth restriction (IUGR), intrahepatic cholestasis of pregnancy and gestational diabetes, were assessed for their ABCA1 and ABCG1 expression levels and compared to age-matched control placentas with qRT-PCR and immunohistochemistry. ABCA1 expression was additionally investigated with immunoblot in placental membrane vesicles. Furthermore, placental cholesterol and phospholipid contents were assessed.
  
  
  RESULTS
  ABCA1 mRNA levels differed significantly between preterm and term control placentas (p = 0.0013). They were down-regulated in isolated PE and PE with IUGR (p = 0.0006 and p = 0.0012, respectively), but unchanged in isolated IUGR, isolated HELLP and other gestational diseases compared to gestational age-matched controls. Correspondingly, in PE, ABCA1 protein expression was significantly reduced in the apical membrane of the villous syncytiotrophoblast (p = 0.011) and in villous fetal endothelial cells (p = 0.036). Furthermore, in PE there was a significant increase in the placental content of total and individual classes of phospholipids which were partially correlated with diminished ABCA1 expression. Conversely, ABCG1 mRNA and protein levels were stable in the investigated conditions.
  
  
  CONCLUSIONS
  In gestational disease, there is a specific down-regulation of placental ABCA1 expression at sites of feto-maternal lipid exchange in PE. At a functional level, the increase in placental lipid concentrations provides indirect evidence of an impaired transport capacity of ABCA1 in this disease.
authors.affiliation: Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland; Department of Obstetrics and Gynecology, University Hospital, University of Bern, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Baumann
authors.forename: M
authors.initials: M
authors.lastname: Körner
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: Wenger
authors.forename: D
authors.initials: D
authors.lastname: Surbek
authors.forename: C
authors.initials: C
authors.lastname: Albrecht
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D002780:Cholestasis, Intrahepatic / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D016640:Diabetes, Gestational / Q000378:metabolism / Q000473:pathology; D005321:Extraembryonic Membranes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D017359:HELLP Syndrome / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D010929:Placentation; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000473:pathology; D047928:Premature Birth / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger
keywords: ABCA1; ABCG1; IUGR; Placenta; Pre-eclampsia