925
Views
38
CrossRef citations to date
0
Altmetric
Review

Regulation of drug transporter expression and function in the placenta

, PhD (Professor) &

Bibliography

  • Sandovici I, Hoelle K, Angiolini E, Constancia M. Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming. Reprod Biomed Online 2012;25(1):68–89
  • Lager S, Powell TL. Regulation of nutrient transport across the placenta. J Pregnancy 2012;2012:179827
  • Daw JR, Hanley GE, Greyson DL, Morgan SG. Prescription drug use during pregnancy in developed countries: a systematic review. Pharmacoepidemiol Drug Saf 2011;20(9):895–902
  • Vahakangas K, Myllynen P. Drug transporters in the human blood-placental barrier. Br J Pharmacol 2009;158(3):665–78
  • Staud F, Cerveny L, Ceckova M. Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure. J Drug Target 2012;20(9):736–63
  • Dean M, Annilo T. Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates. Annu Rev Genomics Hum Genet 2005;6:123–42
  • Szakacs G, Paterson JK, Ludwig JA, et al. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006;5(3):219–34
  • Ceckova-Novotna M, Pavek P, Staud F. P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol 2006;22(3):400–10
  • Hahnova-Cygalova L, Ceckova M, Staud F. Fetoprotective activity of breast cancer resistance protein (BCRP, ABCG2): expression and function throughout pregnancy. Drug Metab Rev 2010;43(1):53–68
  • Atkinson DE, Greenwood SL, Sibley CP, et al. Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. Am J Physiol Cell Physiol 2003;285(3):C584–91
  • Meyer zu Schwabedissen HE, Jedlitschky G, Gratz M, et al. Variable expression of MRP2 (ABCC2) in human placenta: influence of gestational age and cellular differentiation. Drug Metab Dispos 2005;33(7):896–904
  • Pascolo L, Fernetti C, Pirulli D, et al. Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells. Biochem Biophys Res Commun 2003;303(1):259–65
  • Serrano MA, Macias RI, Briz O, et al. Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta. Placenta 2007;28(2-3):107–17
  • St-Pierre MV, Serrano MA, Macias RI, et al. Expression of members of the multidrug resistance protein family in human term placenta. Am J Physiol Regul Integr Comp Physiol 2000;279(4):R1495–503
  • May K, Minarikova V, Linnemann K, et al. Role of the multidrug transporter proteins ABCB1 and ABCC2 in the diaplacental transport of talinolol in the term human placenta. Drug Metab Dispos 2008;36(4):740–4
  • Koepsell H, Endou H. The SLC22 drug transporter family. Pflugers Arch 2004;447(5):666–76
  • Staud F, Cerveny L, Ahmadimoghaddam D, Ceckova M. Multidrug and toxin extrusion proteins (MATE/SLC47); role in pharmacokinetics. Int J Biochem Cell Biol 2013;45(9):2007–11
  • Klaassen CD, Aleksunes LM. Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol Rev 2010;62(1):1–96
  • Klaassen CD, Lu H, Cui JY. Epigenetic regulation of drug processing genes. Toxicol Mech Methods 2011;21(4):312–24
  • Staudinger JL, Woody S, Sun M, Cui W. Nuclear-receptor-mediated regulation of drug- and bile-acid-transporter proteins in gut and liver. Drug Metab Rev 2013;45(1):48–59
  • Geenes VL, Dixon PH, Chambers J, et al. Characterisation of the nuclear receptors FXR, PXR and CAR in normal and cholestatic placenta. Placenta 2011;32(7):535–7
  • Mathias AA, Hitti J, Unadkat JD. P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages. Am J Physiol Regul Integr Comp Physiol 2005;289(4):R963–9
  • Nishimura M, Naito S, Yokoi T. Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies. Drug Metab Pharmacokinet 2004;19(2):135–49
  • Jiang YZ, Wang K, Fang R, Zheng J. Expression of aryl hydrocarbon receptor in human placentas and fetal tissues. J Histochem Cytochem 2010;58(8):679–85
  • Stejskalova L, Vecerova L, Perez LM, et al. Aryl hydrocarbon receptor and aryl hydrocarbon nuclear translocator expression in human and rat placentas and transcription activity in human trophoblast cultures. Toxicol Sci 2011;123(1):26–36
  • Wang H, Wu X, Hudkins K, et al. Expression of the breast cancer resistance protein (Bcrp1/Abcg2) in tissues from pregnant mice: effects of pregnancy and correlations with nuclear receptors. Am J Physiol Endocrinol Metab 2006;291(6):E1295–304
  • Pospechova K, Rozehnal V, Stejskalova L, et al. Expression and activity of vitamin D receptor in the human placenta and in choriocarcinoma BeWo and JEG-3 cell lines. Mol Cell Endocrinol 2009;299(2):178–87
  • Pavek P, Smutny T. Nuclear receptors in regulation of biotransformation enzymes and drug transporters in the placental barrier. Drug Metab Rev 2014;46(1):19–32
  • Gahir SS, Piquette-Miller M. Gestational and pregnane X receptor-mediated regulation of placental ATP-binding cassette drug transporters in mice. Drug Metab Dispos 2011;39(3):465–71
  • Evseenko DA, Paxton JW, Keelan JA. Independent regulation of apical and basolateral drug transporter expression and function in placental trophoblasts by cytokines, steroids, and growth factors. Drug Metab Dispos 2007;35(4):595–601
  • Oda K, Nishimura T, Higuchi K, et al. Estrogen receptor alpha induction by mitoxantrone increases Abcg2 expression in placental trophoblast cells. J Pharm Sci 2013;102(9):3364–72
  • Wang H, Unadkat JD, Mao Q. Hormonal regulation of BCRP expression in human placental BeWo cells. Pharm Res 2008;25(2):444–52
  • Pavek P, Cerveny L, Svecova L, et al. Examination of Glucocorticoid receptor alpha-mediated transcriptional regulation of P-glycoprotein, CYP3A4, and CYP2C9 genes in placental trophoblast cell lines. Placenta 2007;28(10):1004–11
  • Manceau S, Giraud C, Decleves X, et al. ABC drug transporter and nuclear receptor expression in human cytotrophoblasts: influence of spontaneous syncytialization and induction by glucocorticoids. Placenta 2012;33(11):927–32
  • Mason CW, Lee GT, Dong Y, et al. Effect of prostaglandin e2 on multidrug resistance transporters in human placental cells. Drug Metab Dispos 2014;42(12):2077–86
  • Blazquez AG, Briz O, Gonzalez-Sanchez E, et al. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis. Toxicol Appl Pharmacol 2014;277(1):77–85
  • Svoboda M, Riha J, Wlcek K, et al. Organic anion transporting polypeptides (OATPs): regulation of expression and function. Curr Drug Metab 2011;12(2):139–53
  • Chang TT, Shyu MK, Huang MC, et al. Hypoxia-mediated down-regulation of OCTN2 and PPARalpha expression in human placentas and in BeWo cells. Mol Pharm 2011;8(1):117–25
  • Tanabe M, Ieiri I, Nagata N, et al. Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J Pharmacol Exp Ther 2001;297(3):1137–43
  • Hitzl M, Schaeffeler E, Hocher B, et al. Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1). Pharmacogenetics 2004;14(5):309–18
  • Hemauer SJ, Nanovskaya TN, Abdel-Rahman SZ, et al. Modulation of human placental P-glycoprotein expression and activity by MDR1 gene polymorphisms. Biochem Pharmacol 2010;79(6):921–5
  • Wang C, Xie L, Zhou K, et al. Increased risk for congenital heart defects in children carrying the ABCB1 Gene C3435T polymorphism and maternal periconceptional toxicants exposure. PLoS One 2013;8(7):e68807
  • Li J, Wang ZN, Chen YP, et al. Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life. Clin Lab 2012;58(9-10):1085–9
  • Ieiri I. Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Drug Metab Pharmacokinet 2012;27(1):85–105
  • Kobayashi D, Ieiri I, Hirota T, et al. Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metab Dispos 2005;33(1):94–101
  • Wang C, Xie L, Li H, et al. Associations between ABCG2 gene polymorphisms and isolated septal defects in a han Chinese population. DNA Cell Biol 2014;33(10):689–98
  • Hutson JR, Koren G, Matthews SG. Placental P-glycoprotein and breast cancer resistance protein: influence of polymorphisms on fetal drug exposure and physiology. Placenta 2010;31(5):351–7
  • Pollex EK, Anger G, Hutson J, et al. Breast cancer resistance protein (BCRP)-mediated glyburide transport: effect of the C421A/Q141K BCRP single-nucleotide polymorphism. Drug Metab Dispos 2012;38(5):740–4
  • Daud AN, Bergman JE, Bakker MK, et al. Pharmacogenetics of drug-induced birth defects: the role of polymorphisms of placental transporter proteins. Pharmacogenomics 2014;15(7):1029–41
  • Tertti K, Petsalo A, Niemi M, et al. Transfer of repaglinide in the dually perfused human placenta and the role of organic anion transporting polypeptides (OATPs). Eur J Pharm Sci 2011;44(3):181–6
  • Maccani MA, Marsit CJ. Epigenetics in the placenta. Am J Reprod Immunol 2009;62(2):78–89
  • Ng RK, Dean W, Dawson C, et al. Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5. Nat Cell Biol 2008;10(11):1280–90
  • Ingelman-Sundberg M, Zhong XB, Hankinson O, et al. Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metab Dispos 2013;41(10):1725–31
  • Schroeder DI, LaSalle JM. How has the study of the human placenta aided our understanding of partially methylated genes? Epigenomics 2013;5(6):645–54
  • Ehrlich M, Gama-Sosa MA, Huang LH, et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 1982;10(8):2709–21
  • Schroeder DI, Blair JD, Lott P, et al. The human placenta methylome. Proc Natl Acad Sci USA 2013;110(15):6037–42
  • Lister R, Pelizzola M, Kida YS, et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 2011;471(7336):68–73
  • Gama-Sosa MA, Midgett RM, Slagel VA, et al. Tissue-specific differences in DNA methylation in various mammals. Biochim Biophys Acta 1983;740(2):212–19
  • Novakovic B, Yuen RK, Gordon L, et al. Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors. BMC Genomics 2011;12:529
  • Takane H, Kobayashi D, Hirota T, et al. Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene. J Pharmacol Exp Ther 2004;311(3):1179–87
  • Ciarimboli G. Membrane transporters as mediators of cisplatin side-effects. Anticancer Res 2014;34(1):547–50
  • Chen L, Hong C, Chen EC, et al. Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3. Pharmacogenomics J 2013;13(2):110–20
  • Imai S, Kikuchi R, Tsuruya Y, et al. Epigenetic regulation of organic anion transporting polypeptide 1B3 in cancer cell lines. Pharm Res 2013;30(11):2880–90
  • Kikuchi R, Yagi S, Kusuhara H, et al. Genome-wide analysis of epigenetic signatures for kidney-specific transporters. Kidney Int 2010;78(6):569–77
  • Saito J, Hirota T, Kikunaga N, et al. Interindividual differences in placental expression of the SLC22A2 (OCT2) gene: relationship to epigenetic variations in the 5’-upstream regulatory region. J Pharm Sci 2011;100(9):3875–83
  • Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75(5):843–54
  • Ikemura K, Iwamoto T, Okuda M. MicroRNAs as regulators of drug transporters, drug-metabolizing enzymes, and tight junctions: implication for intestinal barrier function. Pharmacol Ther 2014;143(2):217–24
  • Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120(1):15–20
  • Gu Y, Sun J, Groome LJ, Wang Y. Differential miRNA expression profiles between the first and third trimester human placentas. Am J Physiol Endocrinol Metab 2013;304(8):E836–43
  • Pineles BL, Romero R, Montenegro D, et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol 2007;196(3):261; e261-266
  • Zhu XM, Han T, Sargent IL, et al. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol 2009;200(6):661; e661-667
  • To KK. MicroRNA: a prognostic biomarker and a possible druggable target for circumventing multidrug resistance in cancer chemotherapy. J Biomed Sci 2013;20:99
  • Haenisch S, Werk AN, Cascorbi I. MicroRNAs and their relevance to ABC transporters. Br J Clin Pharmacol 2014;77(4):587–96
  • Lim CH, Jeong W, Lim W, et al. Differential expression of select members of the SLC family of genes and regulation of expression by microRNAs in the chicken oviduct. Biol Reprod 2012;87(6):145
  • Baudry A, Mouillet-Richard S, Schneider B, et al. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science 2010;329(5998):1537–41
  • Dalmasso G, Nguyen HT, Yan Y, et al. MicroRNA-92b regulates expression of the oligopeptide transporter PepT1 in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2011;300(1):G52–9
  • Henrique R, Oliveira AI, Costa VL, et al. Epigenetic regulation of MDR1 gene through post-translational histone modifications in prostate cancer. BMC Genomics 2013;14:898
  • Tomiyasu H, Goto-Koshino Y, Fujino Y, et al. Epigenetic regulation of the ABCB1 gene in drug-sensitive and drug-resistant lymphoid tumour cell lines obtained from canine patients. Vet J 2014;199(1):103–9
  • Baker EK, Johnstone RW, Zalcberg JR, El-Osta A. Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene 2005;24(54):8061–75
  • Huo H, Magro PG, Pietsch EC, et al. Histone methyltransferase MLL1 regulates MDR1 transcription and chemoresistance. Cancer Res 2010;70(21):8726–35
  • Jiang ZP, Xu P, Wang GP, et al. Hypothesizing that histone deacetylase inhibitors can be used to reverse multiple drug resistance. Med Hypotheses 2010;74(1):92–4
  • Wagschal A, Sutherland HG, Woodfine K, et al. G9a histone methyltransferase contributes to imprinting in the mouse placenta. Mol Cell Biol 2008;28(3):1104–13
  • Lujambio A, Esteller M. CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle 2007;6(12):1455–9
  • Saito J, Hirota T, Furuta S, et al. Association between DNA methylation in the miR-328 5’-flanking region and inter-individual differences in miR-328 and BCRP expression in human placenta. PLoS One 2013;8(8):e72906
  • Fu D, Arias IM. Intracellular trafficking of P-glycoprotein. Int J Biochem Cell Biol 2012;44(3):461–4
  • Kipp H, Arias IM. Intracellular trafficking and regulation of canalicular ATP-binding cassette transporters. Semin Liver Dis 2000;20(3):339–51
  • Jedlitschky G, Hoffmann U, Kroemer HK. Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin Drug Metab Toxicol 2006;2(3):351–66
  • Noack A, Noack S, Hoffmann A, et al. Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C. PLoS One 2014;9(2):e88154
  • Zhang Z, Wu JY, Hait WN, Yang JM. Regulation of the stability of P-glycoprotein by ubiquitination. Mol Pharmacol 2004;66(3):395–403
  • Kock K, Koenen A, Giese B, et al. Rapid modulation of the organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) function by protein kinase C-mediated internalization. J Biol Chem 2010;285(15):11336–47
  • Maeda K, Sugiyama Y. Transporter biology in drug approval: regulatory aspects. Mol Aspects Med 2013;34(2-3):711–18
  • Feinshtein V, Erez O, Ben-Zvi Z, et al. Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: an ex vivo study. Am J Obstet Gynecol 2013;209(6):573; e571-573 e515
  • Pollex E, Lubetsky A, Koren G. The role of placental breast cancer resistance protein in the efflux of glyburide across the human placenta. Placenta 2008;29(8):743–7
  • Donofrio MT, Moon-Grady AJ, Hornberger LK, et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation 2014;129(21):2183–242
  • Wang C, Li H, Zhou K, et al. Sodium tanshinone IIA sulfonate and sodium danshensu open the placental barrier through down-regulation of placental P-glycoprotein in mice: implications in the transplacental digoxin treatment for fetal heart failure. Int J Cardiol 2014;176(3):1331–3
  • Gulati A, Gerk PM. Role of placental ATP-binding cassette (ABC) transporters in antiretroviral therapy during pregnancy. J Pharm Sci 2009;98(7):2317–35
  • Molsa M, Heikkinen T, Hakkola J, et al. Functional role of P-glycoprotein in the human blood-placental barrier. Clin Pharmacol Ther 2005;78(2):123–31
  • Sudhakaran S, Ghabrial H, Nation RL, et al. Differential bidirectional transfer of indinavir in the isolated perfused human placenta. Antimicrob Agents Chemother 2005;49(3):1023–8
  • Vinot C, Gavard L, Treluyer JM, et al. Placental transfer of maraviroc in an ex vivo human cotyledon perfusion model and influence of ABC transporter expression. Antimicrob Agents Chemother 2013;57(3):1415–20
  • Gil S, Saura R, Forestier F, Farinotti R. P-glycoprotein expression of the human placenta during pregnancy. Placenta 2005;26(2-3):268–70
  • Lye P, Bloise E, Dunk C, et al. Effect of oxygen on multidrug resistance in the first trimester human placenta. Placenta 2012;34(9):817–23
  • Sun M, Kingdom J, Baczyk D, et al. Expression of the multidrug resistance P-glycoprotein, (ABCB1 glycoprotein) in the human placenta decreases with advancing gestation. Placenta 2006;27(6-7):602–9
  • Petropoulos S, Kalabis GM, Gibb W, Matthews SG. Functional changes of mouse placental multidrug resistance phosphoglycoprotein (ABCB1) with advancing gestation and regulation by progesterone. Reprod Sci 2007;14(4):321–8
  • Javam M, Audette MC, Iqbal M, et al. Effect of oxygen on multidrug resistance in term human placenta. Placenta 2014;35(5):324–30
  • Novotna M, Libra A, Kopecky M, et al. P-glycoprotein expression and distribution in the rat placenta during pregnancy. Reprod Toxicol 2004;18(6):785–92
  • Yeboah D, Sun M, Kingdom J, et al. Expression of breast cancer resistance protein (BCRP/ABCG2) in human placenta throughout gestation and at term before and after labor. Can J Physiol Pharmacol 2006;84(12):1251–8
  • Ceckova M, Libra A, Pavek P, et al. Expression and functional activity of breast cancer resistance protein (BCRP, ABCG2) transporter in the human choriocarcinoma cell line BeWo. Clin Exp Pharmacol Physiol 2006;33(1-2):58–65
  • Meyer zu Schwabedissen HE, Grube M, Dreisbach A, et al. Epidermal growth factor-mediated activation of the map kinase cascade results in altered expression and function of ABCG2 (BCRP). Drug Metab Dispos 2006;34(4):524–33
  • Kalabis GM, Petropoulos S, Gibb W, Matthews SG. Breast cancer resistance protein (Bcrp1/Abcg2) in mouse placenta and yolk sac: ontogeny and its regulation by progesterone. Placenta 2007;28(10):1073–81
  • Yasuda S, Itagaki S, Hirano T, Iseki K. Expression level of ABCG2 in the placenta decreases from the mid stage to the end of gestation. Biosci Biotechnol Biochem 2005;69(10):1871–6
  • Otsuka M, Matsumoto T, Morimoto R, et al. A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci USA 2005;102(50):17923–8
  • Ahmadimoghaddam D, Zemankova L, Nachtigal P, et al. Organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter in the placenta and fetal tissues: expression profile and fetus protective role at different stages of gestation. Biol Reprod 2013;88(3):55
  • Lee N, Hebert MF, Prasad B, et al. Effect of gestational age on mRNA and protein expression of polyspecific organic cation transporters during pregnancy. Drug Metab Dispos 2013;41(12):2225–32
  • Shuster DL, Bammler TK, Beyer RP, et al. Gestational age-dependent changes in gene expression of metabolic enzymes and transporters in pregnant mice. Drug Metab Dispos 2013;41(2):332–42
  • Gauster M, Desoye G, Totsch M, Hiden U. The placenta and gestational diabetes mellitus. Curr Diab Rep 2012;12(1):16–23
  • Ruchat SM, Houde AA, Voisin G, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics 2013;8(9):935–43
  • Nomura Y, Lambertini L, Rialdi A, et al. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod Sci 2014;21(1):131–7
  • Anger GJ, Cressman AM, Piquette-Miller M. Expression of ABC Efflux transporters in placenta from women with insulin-managed diabetes. PLoS One 2012;7(4):e35027
  • Slaviero KA, Clarke SJ, Rivory LP. Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 2003;4(4):224–32
  • Wang JH, Scollard DA, Teng S, et al. Detection of P-glycoprotein activity in endotoxemic rats by 99mTc-sestamibi imaging. J Nucl Med 2005;46(9):1537–45
  • Petrovic V, Wang JH, Piquette-Miller M. Effect of endotoxin on the expression of placental drug transporters and glyburide disposition in pregnant rats. Drug Metab Dispos 2008;36(9):1944–50
  • Petrovic V, Piquette-Miller M. Impact of polyinosinic/polycytidylic acid on placental and hepatobiliary drug transporters in pregnant rats. Drug Metab Dispos 2010;38(10):1760–6
  • Petropoulos S, Gibb W, Matthews SG. Glucocorticoid regulation of placental breast cancer resistance protein (Bcrp1) in the mouse. Reprod Sci 2011;18(7):631–9
  • Petropoulos S, Gibb W, Matthews SG. Breast cancer-resistance protein (BCRP1) in the fetal mouse brain: development and glucocorticoid regulation. Biol Reprod 2011;84(4):783–9
  • Petropoulos S, Gibb W, Matthews SG. Effect of glucocorticoids on regulation of placental multidrug resistance phosphoglycoprotein (P-gp) in the mouse. Placenta 2010;31(9):803–10
  • Patel J, Landers K, Mortimer RH, Richard K. Regulation of hypoxia inducible factors (HIF) in hypoxia and normoxia during placental development. Placenta 2010;31(11):951–7
  • Lye P, Bloise E, Dunk C, et al. Effect of oxygen on multidrug resistance in the first trimester human placenta. Placenta 2013;34(9):817–23
  • Comerford KM, Wallace TJ, Karhausen J, et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 2002;62(12):3387–94
  • Rytting E, Audus KL. Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells. J Pharm Pharmacol 2007;59(8):1095–102
  • Iqbal M, Audette MC, Petropoulos S, et al. Placental drug transporters and their role in fetal protection. Placenta 2012;33(3):137–42
  • Yuen RK, Chen B, Blair JD, et al. Hypoxia alters the epigenetic profile in cultured human placental trophoblasts. Epigenetics 2013;8(2):192–202
  • Jones HN, Powell TL, Jansson T. Regulation of placental nutrient transport-a review. Placenta 2007;28(8-9):763–74
  • Cui T, Liu Y, Men X, et al. Bile acid transport correlative protein mRNA expression profile in human placenta with intrahepatic cholestasis of pregnancy. Saudi Med J 2009;30(11):1406–10
  • Azzaroli F, Mennone A, Feletti V, et al. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid. Aliment Pharmacol Ther 2007;26(8):1139–46
  • Azzaroli F, Raspanti ME, Simoni P, et al. High doses of ursodeoxycholic acid up-regulate the expression of placental breast cancer resistance protein in patients affected by intrahepatic cholestasis of pregnancy. PLoS One 2013;8(5):e64101
  • WHO. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. Recommendations for a public health approach (2010 version). Available from: http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf [Accessed 29 May 2013]
  • Kis O, Robillard K, Chan GN, Bendayan R. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci 2009;31(1):22–35
  • Camus M, Delomenie C, Didier N, et al. Increased expression of MDR1 mRNAs and P-glycoprotein in placentas from HIV-1 infected women. Placenta 2006;27(6-7):699–706
  • Papp E, Gadawski I, Cote HC. Longitudinal effects of thymidine analogues on mtDNA, mtRNA and multidrug resistance (MDR-1) induction in cultured cells. J Antimicrob Chemother 2008;61(5):1048–52
  • Triunfo S, Scambia G. Cancer in pregnancy: diagnosis, treatment and neonatal outcome. Minerva Ginecol 2014;66(3):325–34
  • Vetter G, Zimmermann F, Bruder E, et al. Aggressive breast cancer during pregnancy with a rare form of metastasis in the maternal placenta. Geburtshilfe Frauenheilkd 2014;74(6):579–82
  • Isoherranen N, Thummel KE. Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes? Drug Metab Dispos 2013;41(2):256–62
  • van Gelder MM, van Rooij IA, de Jong-van den Berg LT, Roeleveld N. Teratogenic mechanisms associated with prenatal medication exposure. Therapie 2014;69(1):13–24
  • Marzolini C, Rudin C, Decosterd LA, Swiss Mother + Child HIVCS. Transplacental passage of protease inhibitors at delivery. AIDS 2002;16(6):889–93
  • Onwuchuruba CN, Towers CV, Howard BC, et al. Transplacental passage of vancomycin from mother to neonate. Am J Obstet Gynecol 2014;210(4):352; e351-354
  • Schneider H, Panigel M, Dancis J. Transfer across the perfused human placenta of antipyrine, sodium and leucine. Am J Obstet Gynecol 1972;114(6):822–8
  • Atkinson DE, Sibley CP, Fairbairn LJ, Greenwood SL. MDR1 P-gp expression and activity in intact human placental tissue; upregulation by retroviral transduction. Placenta 2006;27(6-7):707–14
  • Greenwood SL, Sibley CP. In vitro methods for studying human placental amino acid transport placental villous fragments. Methods Mol Med 2006;122:253–64
  • Glazier JD, Sibley CP. In vitro methods for studying human placental amino acid transport: placental plasma membrane vesicles. Methods Mol Med 2006;122:241–52
  • Ushigome F, Takanaga H, Matsuo H, et al. Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein. Eur J Pharmacol 2000;408(1):1–10
  • Wadsack C, Hammer A, Levak-Frank S, et al. Selective cholesteryl ester uptake from high density lipoprotein by human first trimester and term villous trophoblast cells. Placenta 2003;24(2-3):131–43
  • Utoguchi N, Chandorkar GA, Avery M, Audus KL. Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells. Reprod Toxicol 2000;14(3):217–24
  • Evseenko DA, Paxton JW, Keelan JA. ABC drug transporter expression and functional activity in trophoblast-like cell lines and differentiating primary trophoblast. Am J Physiol Regul Integr Comp Physiol 2006;290(5):R1357–65
  • Li H, van Ravenzwaay B, Rietjens IM, Louisse J. Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds. Arch Toxicol 2013;87(9):1661–9
  • Cygalova L, Ceckova M, Pavek P, Staud F. Role of breast cancer resistance protein (Bcrp/Abcg2) in fetal protection during gestation in rat. Toxicol Lett 2008;178(3):176–80
  • Ahmadimoghaddam D, Hofman J, Zemankova L, et al. Synchronized activity of organic cation transporter 3 (Oct3/Slc22a3) and multidrug and toxin extrusion 1 (Mate1/Slc47a1) transporter in transplacental passage of MPP+ in rat. Toxicol Sci 2012;128(2):471–81
  • Ahmadimoghaddam D, Staud F. Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein. Reprod Toxicol 2013;39:17–22
  • Cygalova LH, Hofman J, Ceckova M, Staud F. Transplacental pharmacokinetics of glyburide, rhodamine 123, and BODIPY FL prazosin: effect of drug efflux transporters and lipid solubility. J Pharmacol Exp Ther 2009;331(3):1118–25
  • Goeden N, Bonnin A. Ex vivo perfusion of mid-to-late-gestation mouse placenta for maternal-fetal interaction studies during pregnancy. Nat Protoc 2013;8(1):66–74
  • Neumanova Z, Cerveny L, Ceckova M, Staud F. Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta. AIDS 2014;28(1):9–17
  • Weatherley AJ, Ross R, Pickard DW, Care AD. The transfer of calcium during perfusion of the placenta and intact and thyroparathyroidectomized sheep. Placenta 1983;4(3):271–7
  • Staud F, Vackova Z, Pospechova K, et al. Expression and transport activity of breast cancer resistance protein (Bcrp/Abcg2) in dually perfused rat placenta and HRP-1 cell line. J Pharmacol Exp Ther 2006;319(1):53–62
  • Slikker WJr, Bailey JR, Newport D, et al. Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey. J Pharmacol Exp Ther 1982;223(2):483–9
  • Jonker JW, Buitelaar M, Wagenaar E, et al. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci USA 2002;99(24):15649–54
  • Smit JW, Huisman MT, van Tellingen O, et al. Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest 1999;104(10):1441–7
  • Tang SC, de Vries N, Sparidans RW, et al. Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) gene dosage on plasma pharmacokinetics and brain accumulation of dasatinib, sorafenib, and sunitinib. J Pharmacol Exp Ther 2013;346(3):486–94
  • Novak D, Quiggle F, Artime C, Beveridge M. Regulation of glutamate transport and transport proteins in a placental cell line. Am J Physiol Cell Physiol 2001;281(3):C1014–22
  • Abduljalil K, Furness P, Johnson TN, et al. Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling. Clin Pharmacokinet 2012;51(6):365–96
  • Gaohua L, Abduljalil K, Jamei M, et al. A pregnancy physiologically based pharmacokinetic (p-PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4. Br J Clin Pharmacol 2012;74(5):873–85
  • Chernyavsky IL, Jensen OE, Leach L. A mathematical model of intervillous blood flow in the human placentone. Placenta 2010;31(1):44–52
  • Panitchob N, Widdows KL, Crocker IP, et al. Computational modelling of amino acid exchange and facilitated transport in placental membrane vesicles. J Theor Biol 2014;365C:352–64
  • Lu G, Abduljalil K, Jamei M, et al. Physiologically-based pharmacokinetic (PBPK) models for assessing the kinetics of xenobiotics during pregnancy: achievements and shortcomings. Curr Drug Metab 2012;13(6):695–720
  • Kalabis GM, Kostaki A, Andrews MH, et al. Multidrug resistance phosphoglycoprotein (ABCB1) in the mouse placenta: fetal protection. Biol Reprod 2005;73(4):591–7

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.