title: ATP-binding cassette proteins BCRP, MRP1 and P-gp expression and localization in the human umbilical cord.
abstract: 1. The umbilical cord is a direct conduit to the fetus hence transporters could have roles in partitioning substances between the maternal-placental-fetal units. Here we determined the expression and localization of the ATP-Binding Cassette (ABC) transporters BCRP (ABCG2), P-gp (ABCB1) and MRP1 (ABCC1) in human umbilical cords. 2. The mRNA for BCRP and MRP1 was detected in 25/25 samples, but P-gp was detected in only 5/25. ABC transporter mRNA expression relative to 18S was 25.6 ± 0.3, 26.5 ± 0.6 and 22.2 ± 0.2 cycles for BCRP, MRP1 and P-gp respectively. 3. Using a subset of 10 umbilical cords, BCRP protein was present in all samples (immunoblot) with positive correlation between mRNA and proteins (p = 0.07, r = 0.62) and between immunoblotting and immunohistochemistry (IHC) (p = 0.03, r = 0.67). P-gp protein was observed in 4/10 samples by both immunoblot and IHC, with no correlation between mRNA and protein (p = 0.45, r = 0.55) or immunoblotting and IHC (p = 0.2, r = 0.72), likely due to small sample size. MRP1 protein was not observed. 4. Localization of BCRP and P-gp proteins was to Wharton's jelly with no specific staining in arterial or venous endothelia. 5. Understanding ABC transporter expression in the umbilical cord may be useful for determining fetal exposures to xenobiotics if functional properties can be defined.
authors.affiliation: a Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada and.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Riches
authors.affiliation: a Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada and.
authors.forename: Gurinder
authors.initials: G
authors.lastname: Walia
authors.affiliation: a Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada and.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Berman
authors.affiliation: b Department of Obstetrics , Gynecology and Women's Health, John A. Burns School of Medicine, Kapi'Olani Medical Center for Women and Children , Honolulu , HI , USA.
authors.forename: Tricia E
authors.initials: TE
authors.lastname: Wright
authors.affiliation: a Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada and.
authors.forename: Abby C
authors.initials: AC
authors.lastname: Collier
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D014470:Umbilical Cord / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1
keywords: Developmental toxicology; fetal exposure; pregnancy; transporters