title: Immunolocalization of ABC drug transporters in human placenta from normal and gestational diabetic pregnancies.
abstract: OBJECTIVE
  ABC transporters, P-gp, MDR3, BCRP and MRP1, can bind both endo- and exogenous ligands. The latter include immunosuppressive, anticancer sedative, anticonvulsant, antiparasitic and cardiovascular drugs, as well as HIV protease inhibitors and antibiotics. Protein transporters are also involved in tissue distribution of orally administered medicines in combination therapy for gestational diabetes mellitus (GDM) and could be used during GDM treatment. The distribution depends on transporter specificity its expression and subcellular localization.
  
  
  OBJECTIVE
  The aim of the study was to compare P-gp, MDR3, BCRP and MRP1 localization in placental tissues from normal and GDM diabetic pregnancies.
  
  
  METHODS
  Tissue samples were taken from 10 normal and 10 GDM placentas. Immunohistochemical reactions were performed with the use of adequate monoclonal antibodies. Avidin-biotin-peroxidase complex method was used for the visualization of antigen-antibody complexes.
  
  
  RESULTS
  P-gp, MDR3 and BCRP were found in all parts of normal human placenta i.e. the amniotic epithelium, cytotrophoblast, syncytiotrophoblast and decidual cells. P-gp and BCRP, but not MDR3 and MRP1, were also localized on the endothelial cells of fetal blood vessels in the chorionic plate, as well as stem and tertiary villi. MRP1 expression was observed in the cytotrophoblast and the syncytiotrophoblast. Its expression was very low or undetectable in the amniotic epithelium and the majority of decidual cells. Immunohistochemical reactions within the syncytiotrophoblast showed apical (P-gp, BCRP), apical and basal (MRP1) or diffuse (MDR3) distribution. The main changes observed in GDM placentas included weaker MRP1 and MDR3 positive reactions in the syncytiotrophoblast, slightly lower expression of P-gp in the decidual and amniotic epithelial cells, and MDR3 in the amniotic epithelium.
  
  
  CONCLUSIONS
  Our results indicate that GDM-related changes in the environment of placental cells do not substantially influence tissue and subcellular location of ABC transporters. Nevertheless, the expression of P-gp, MDR3 and MRP1 may be lower in comparison to normal placentas. Basal syncytiotrophoblast transporters, MRP1 and MDR3, seem to be more sensitive to the influence of GDM than apical proteins, what may result in altered biodisposition of endogenous substrates and drugs.
authors.forename: Danuta
authors.initials: D
authors.lastname: Kozłowska-Rup
authors.forename: Piotr
authors.initials: P
authors.lastname: Czekaj
authors.forename: Danuta
authors.initials: D
authors.lastname: Plewka
authors.forename: Jerzy
authors.initials: J
authors.lastname: Sikora
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000936:Antigen-Antibody Complex; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C095122:multidrug resistance protein 3; C421109:multidrug resistance-associated protein 1