Gestational age‐dependent gene expression profiling of ATP ‐binding cassette transporters in the healthy human placenta

TheATP‐binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal‐fetal interface. We and others have demonstrated a gestational age‐dependent expression pattern of twoABCtransporters, P‐glycoprotein and breast cancer resistance protein throughout pregnancy. However, no reports have comprehensively elucidated the expression pattern of all 50ABCproteins, comparing first trimester and term human placentae. We hypothesized that placentalABCtransporters are expressed in a gestational‐age dependent manner in normal human pregnancy. Using the TaqMan®HumanABCTransporter Array, we assessed themRNAexpression of all 50ABCtransporters in first (first trimester, n = 8) and third trimester (term, n = 12) human placentae and validated the resulting expression of selectedABCtransporters usingqPCR, Western blot and immunohistochemistry. A distinct gene expression profile of 30ABCtransporters was observed comparing first trimestervs. term placentae. Using individualqPCRin selected genes, we validated the increased expression ofABCA1(P < 0.01),ABCA6(P < 0.001),ABCA9(P < 0.001) andABCC3(P < 0.001), as well as the decreased expression ofABCB11(P < 0.001) andABCG4(P < 0.01) with advancing gestation. One important lipid transporter,ABCA6, was selected to correlate protein abundance and characterize tissue localization.ABCA6 exhibited increased protein expression towards term and was predominantly localized to syncytiotrophoblast cells. In conclusion, expression patterns of placentalABCtransporters change as a function of gestational age. These changes are likely fundamental to a healthy pregnancy given the critical role that these transporters play in the regulation of steroidogenesis, immunological responses, and placental barrier function and integrity.