Effect of oxygen on multidrug resistance in the first trimester human placenta

• Published in: Placenta (Eastbourne) 2013-09, Vol.34 (9), p.817-823
• Main Authors: Lye, P, Bloise, E, Dunk, C, Javam, M, Gibb, W, Lye, S.J, Matthews, S.G
• Format: Article
• Language: English
• Subjects: ATP Binding Cassette Transporter, Sub-Family B; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; BCRP; Biological and medical sciences; Cell Hypoxia; Drug Resistance, Multiple; Embryology: invertebrates and vertebrates. Teratology; Female; First-trimester placenta; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Giant Cells - cytology; Giant Cells - drug effects; Giant Cells - metabolism; Humans; Hyperoxia; Hypoxia; Internal Medicine; Multidrug resistance; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Obstetrics and Gynecology; Oxygen - metabolism; P-glycoprotein; Placenta - cytology; Placenta - drug effects; Placenta - metabolism; Placentation; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; RNA, Messenger - metabolism; Tissue Banks; Tissue Culture Techniques; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2013.05.010

Abstract Introduction The multidrug resistance proteins, P-glycoprotein (P-gp, encoded by the ABCB1 gene) and breast cancer resistance protein (BCRP, encoded by ABCG2 ) are highly expressed in the first trimester placenta. These transporters protect the fetus from exposure to maternally derived toxins and xenobiotics. Since oxygen is a regulator of multidrug resistance in various tissues, we hypothesized that changes in oxygen tension alter placental ABCB1 /P-gp and ABCG2 /BCRP expression in the first trimester. Methods Placental specimens were collected from first ( n  = 7), second ( n  = 5) and term pregnancies ( n  = 5). First trimester placental villous explants were incubated (24 or 48 h) in different oxygen tension (3–20%). ABCB1 , ABCG2 and VEGFA mRNA expression levels were assessed by RT-PCR and protein was localized by IHC. Results ABCB1 is expressed most highly in the first trimester placenta ( p