An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus

Abstract

P-glycoprotein (P-gp)/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2 are highly expressed in the placenta and fetus throughout gestation and can modulate exposure and toxicity of drugs and xenobiotics to the vulnerable fetus during the sensitive times of growth and development. We aim to provide an update on current knowledge on placental and fetal expressions of the two transporters in different species, and to provide insight on interpreting transporter expression and fetal exposure relative to the concept of fraction of drug transported. Areas covered: Comprehensive literature review through PubMed (primarily from July 2010 to February 2018) on P-gp and BCRP expression and function in the placenta and fetus of primarily human, mouse, rat, and guinea pig. Expert opinion: While there are many commonalities in the expression and function of P-gp and BCRP in the placenta and fetal tissues across species, there are distinct differences in expression levels and temporal changes. Further studies are needed to quantify protein abundance of these transporters and functionally assess their activities at various gestational stages. Combining the knowledge of interspecies differences and the concept of fraction of drug transported, we may better predict the magnitude of impact these transporters have on fetal drug exposure.

Keywords: ABC transporter; ABCB1; ABCG2; ATP-binding cassette transporter; BCRP; MDR1; P-glycoprotein; P-gp; breast cancer resistance protein; fetus; placenta; pregnancy.

Figure 1:. Schematic illustration of human placenta with cross-section through a chorionic villus.

P-gp and BCRP are localized on the microvillous membrane (apical membrane) of the syncytiotrophoblasts. BCRP is also expressed in fetal capillary endothelium. First trimester immunostaining also revealed BCRP and P-gp expression in the cytotrophoblasts. Arrows indicate the direction of transport. [–, , –67]

Figure 2:. Schematic illustration of rodent placenta (mouse and rat) from the fetal to maternal interface.

P-gp and Bcrp are mainly expressed on the apical membrane of the syncytiotrophoblast layer II. Arrows indicate the direction of transport. Bcrp is also expressed in the fetal capillary endothelium; however, at present, no information is available about cellular localization and function of Bcrp in fetal capillary endothelium. Therefore, the direction of transport of Bcrp in fetal capillary endothelium is unknown. [–, –70]

Figure 3:. Schematic illustration of guinea pig placenta from the fetal to maternal interface.

P-gp is expressed on the apical membrane of the syncytiotrophoblasts. No information is available about Bcrp expression in the placenta and fetus of this species. Arrow indicates the direction of transport. [38, 39]