The multidrug resistance phosphoglycoprotein ATP-binding cassette subfamily B (ABCB1) actively extrudes a range of structurally and functionally diverse xenobiotics as well as glucocorticoids. ABCB1 is present in many cancer cell types as well as in normal tissues. Although it has been localized within the mouse placenta, virtually nothing is known about its regulation. In the mouse, two genes, Abcb1a and Abcb1b, encode ABCB1. We hypothesized that there are changes in placental Abcb1a and Abcb1b gene expression and ABCB1 protein levels during pregnancy. Using in situ hybridization, we demonstrated that Abcb1b mRNA is the predominant placental isoform and that there are profound gestational changes in the expression of both Abcb1a and Abcb1b mRNA. Placentas from pregnant mice were analyzed between Embryonic Days (E) 9.5 and 19 (term approximately 19.5d). Abcb1b mRNA was detected in invading trophoblast cells by E9.5, peaked within the placental labyrinth at E12.5, and then progressively decreased toward term (P < 0.0001). Abcb1a mRNA, although lower than that of Abcb1b at midgestation, paralleled changes in Abcb1b mRNA. Changes in Abcb1 mRNA were reflected by a significant decrease in ABCB1 protein (P < 0.05). A strong correlation existed between placental Abcb1b mRNA and maternal progesterone concentrations, indicating a potential role of progesterone in regulation of placental Abcb1b mRNA. In conclusion, there are dramatic decreases in Abcb1a and Abcb1b mRNA and in ABCB1 at the maternal-fetal interface over the second half of gestation, suggesting that the fetus may become increasingly susceptible to the influences of xenobiotics and natural steroids in the maternal circulation.

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Multidrug resistance phosphoglycoprotein (ABCB1) has been shown to limit maternal-fetal transfer by actively excluding ABCB1 substrates. The authors have previously demonstrated a marked decrease in placental ABCB1 expression in the human and mouse with advancing gestation. In the present study, it is hypothesized that the decrease in ABCB1 expression will result in increased transplacental transfer of ABCB1 substrates over the second half of gestation and that progesterone exhibits a regulatory role on placental ABCB1 expression and function. The authors demonstrate a significant increase in transplacental transfer of [(3)H]digoxin (an ABCB1 substrate) in late gestation (E18.5; P < .001) when compared to earlier embryonic days. Furthermore, maternal plasma progesterone levels did not influence expression or function of ABCB1. The authors conclude that the fetus is increasingly exposed to both endogenous and exogenous substrates of ABCB1 present in the maternal circulation with advancing gestation and that progesterone does not elicit a regulatory role on placental ABCB1 expression or function in vivo.