BCRP/ABCG2 in the Placenta: Expression, Function and Regulation

Abstract

Abstract. Knowledge concerning transport of maternally administered drugs across the placental barrier is essential for determining potential toxicity of drugs to the fetus and the value of drug therapy during pregnancy. An important determinant for fetal drug exposure is the expression of efflux transporters in the placenta. Among human tissues, the ATP-binding cassette efflux transporter BCRP (gene symbol ABCG2) is most abundantly expressed in the apical membrane of placental syncytiotrophoblasts. Although the precise physiological role of BCRP in the placenta is still unclear, existing data strongly suggest that BCRP plays an important role in protecting the fetus against the potential toxicity of drugs, xenobiotics, and metabolites by expelling them across the placental barrier. In this review, we summarize the current knowledge with respect to the expression, function, and polymorphisms of BCRP, as well as transcriptional and posttranscriptional regulation of the transporter in the placenta. Finally, clinical significance of BCRP in the placenta for drug therapy in pregnant women is discussed.

Toxic Effects of Maternal Zearalenone Exposure on Uterine Capacity and Fetal Development in Gestation Rats

“…54 Adenosine triphosphatebinding cassette transporters expressed in the placenta, which have been relatively well defined with respect to their roles in the transport of clinically and toxicologically important drugs/xenobiotics, include P-glycoprotein (ABCB1), the breast cancer resistance protein (ABCG2), and (to a lesser extent) the multidrug resistance proteins 1 to 3 and 5 (ABCC1-3 and 5). [55][56][57] Adenosine triphosphate-binding cassette B1 plays an important role in limiting fetal exposure to various potentially harmful drugs and xenobiotics. 58 This result is in agreement with in vitro studies conducted in the Caco-2 cell line.…”

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

“…These efflux transporters include ABC transporters such as P-glycoprotein (P-gp) or multidrug resistance protein (MDR1), gene symbol ABCB1; breast cancer resistance protein (BCRP) or mitoxantrone resistance protein or placental ABC, gene symbol ABCG2 and multidrug resistance associated proteins (MRP)-1, -2 or -3, gene symbols ABCC1 , ABCC2 , or ABCC3, respectively. These are integral membrane proteins that depend on the energy derived from ATP to drive the transport of substances from the inside of the cell or from the cell membrane out of the cell (12–14). Recently, the mRNA and/or protein expression of these transporters in the fetal membranes; yolk sac and amniotic membranes, and decidua have also been characterized (15–17).…”

Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME

“…Breast cancer resistant protein (BCRP), a member of the ATP-binding cassette transporter family, is highly expressed in the apical membrane of enterocytes and hepatocytes facing bile canaliculus [120, 121]. It is responsible to facilitate intestinal and biliary excretion of several compounds and their metabolites [122–124].…”