title: Organic anion transporter 4 (OAT 4) modifies placental transfer of perfluorinated alkyl acids PFOS and PFOA in human placental ex vivo perfusion system.
abstract: BACKGROUND
  Perfluorinated alkyl acids (PFAAs) are widely used in industry and consumer products. Pregnant women are exposed to PFAAs and their presence in umbilical cord blood represents fetal exposure. Interestingly, PFAAs are substrates for organic anion transporters (OAT) of which OAT4 is expressed in human placenta.
  
  
  METHODS
  To evaluate the contribution of OAT4 and ATP-binding cassette transporter G2 (ABCG2) proteins in the transplacental transfer of perfluoro octane sulfonate (PFOS) and perfluoro octanoate (PFOA) an ex vivo dual recirculating human placental perfusion was used. Altogether 8 placentas from healthy mothers with uncomplicated pregnancies were successfully perfused.
  
  
  RESULTS
  Both PFOS and PFOA crossed the placenta as suggested by in vivo data in the literature. The expression of OAT4 and ABCG2 proteins were studied by immunoblotting and correlation with the transfer index %(TI %) of PFOS and PFOA at 120 and 240 min (n = 4) was studied. The expression of OAT4 was in negative correlation with TI % of PFOA (R(2) = 0.92, p = 0.043) and PFOS (R(2) = 0.99, p = 0.007) at 120 min while at 240 min the correlation was statistically significant only with PFOA. The expression of ABCG2 did not correlate with TI% of PFOS or PFOA.
  
  
  CONCLUSIONS
  Data obtained in this study suggest the involvement of OAT4 in placental passage of PFAAs. Placental passage of PFOS and PFOA is modified by the transporter protein OAT4 but not by ABCG2. This is the first study indicating that OAT4 may decrease the fetal exposure to PFAAs and protect the fetus after maternal exposure to PFAAs but further studies are needed to confirm our findings.
authors: Research Group of Biomedicine, Pharmacology and Toxicology, University of Oulu, Finland; Center for Arctic Medicine, Thule Institute, University of Oulu, Oulu, Finland.
authors: M
authors: M
authors: Kummu
authors: Research Group of Biomedicine, Pharmacology and Toxicology, University of Oulu, Finland; Center for Arctic Medicine, Thule Institute, University of Oulu, Oulu, Finland.
authors: E
authors: E
authors: Sieppi
authors: THL National Institute for Health and Welfare, Department of Environmental Health, Kuopio, Finland.
authors: J
authors: J
authors: Koponen
authors: Department of Gynecology and Obstetrics, Oulu University Hospital, Oulu, Finland.
authors: L
authors: L
authors: Laatio
authors: Faculty of Health Sciences, School of Pharmacy/Toxicology, University of Eastern Finland, Kuopio, Finland.
authors: K
authors: K
authors: Vähäkangas
authors: THL National Institute for Health and Welfare, Department of Environmental Health, Kuopio, Finland.
authors: H
authors: H
authors: Kiviranta
authors: Center for Arctic Medicine, Thule Institute, University of Oulu, Oulu, Finland.
authors: A
authors: A
authors: Rautio
authors: Center for Arctic Medicine, Thule Institute, University of Oulu, Oulu, Finland; Nordlab Oulu, Oulu, Finland. Electronic address: paivi.myllynen@oulu.fi.
authors: P
authors: P
authors: Myllynen
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017738:Alkanesulfonic Acids / Q000378:metabolism*; D002210:Caprylates / Q000378:metabolism*; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D009363:Neoplasm Proteins / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D017738:Alkanesulfonic Acids; D002210:Caprylates; D005466:Fluorocarbons; D009363:Neoplasm Proteins; D029362:Organic Anion Transporters, Sodium-Independent; C427207:SLC22A11 protein, human; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: ABCG2; Fetal exposure; OAT4; PFAA; Perfluoro octane sulphonate; Perfluoro octanoate