Role of breast cancer resistance protein (Bcrp/Abcg2) in fetal protection during gestation in rat

Breast cancer resistance protein (BCRP/ABCG2) is an ABC family drug efflux transporter expressed in a number of physiological tissues including placenta. Here we investigated the expression and function of Bcrp in the rat placenta and fetus during pregnancy. We show that the expression of Bcrp mRNA in placenta peaks on gestation day (gd) 15 and declines significantly to one third up to term. In fetal body tissue, 6.9 and 7.4-fold Bcrp mRNA increase was detected on gds 15 and 18, respectively, compared to the early gd 12. The expression of Bcrp mRNA in fetal organs on gds 18 and 21 is also demonstrated. Additionally, the function of placental and fetal Bcrp during pregnancy was studied by fetal exposure to cimetidine infused to the maternal circulation. The relative amount of drug that penetrated to fetus was highest on gd 12 and decreased to one tenth thereafter. Studies on cimetidine distribution in fetus revealed 2- and 4.4-times lower penetration to the brain on gds 18 and 21, respectively, compared to the whole fetal tissue. Our results indicate that the rat fetus is protected by Bcrp against potentially detrimental substances from gd 15 onwards. Moreover, we propose that the protection of fetus by placental Bcrp is further strengthened by fetal Bcrp.