Placental transporter localization and expression in the human: The importance of species, sex, and gestational age difference

Biology of Reproduction

Volumn 96, Issue 4, 2017, Pages 733-742

  Walker, Natasha ^a   Filis, Panagiotis ^a   Soffientini, Ugo ^b   Bellingham, Michelle ^b   O'Shaughnessy, Peer J ^b   Fowler, Paul A ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

Human; Ontogeny; Placenta; Placental transport

Indexed keywords

ABC TRANSPORTER; ABCB TRANSPORTER; ABCC TRANSPORTER; PLACENTA PROTEIN; PLACENTA TRANSPORTER; SOLUTE CARRIER PROTEIN; UNCLASSIFIED DRUG; CARRIER PROTEIN;

GESTATIONAL AGE; HUMAN; NONHUMAN; ONTOGENY; PLACENTAL TRANSFER; PREGNANCY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REVIEW; SEX DIFFERENCE; SPECIES DIFFERENCE; FEMALE; GENE EXPRESSION REGULATION; GENETICS; MALE; METABOLISM; PHYSIOLOGY; PLACENTA;

FEMALE; GENE EXPRESSION REGULATION; GESTATIONAL AGE; HUMANS; MALE; MEMBRANE TRANSPORT PROTEINS; PLACENTA; PREGNANCY;

EID: 85022344135     PISSN: 00063363     EISSN: 15297268     Source Type: Journal    
DOI: 10.1093/biolre/iox012     Document Type: Review

References (105)

1. Winder NR, Krishnaveni GV, Hill JC, Karat CL, Fall CH, Veena SR, Barker DJ. Placental programming of blood pressure in Indian children. Acta Paediatr 2011; 100:653-660.
2. Yinon Y, Nevo O, Xu J, Many A, Rolfo A, Todros T, Post M, Caniggia I. Severe intrauterine growth restriction pregnancies have increased placental endoglin levels. Am J Pathol 2008; 172(1):77-85.
3. Redman CWG. Current topics: pre-eclampsia and the placenta. Placenta 1991; 12:301-308.
4. Barker DJP. Maternal nutrition, fetal nutrition, and disease in later life. Nutrition 1997; 13:807.
5. Fox H. Aging of the placenta. Arch Dis Child Fetal Neonatal Ed 1997; 77(3):F165-F170.
6. Mikheev AM, Nabekura T, Kaddoumi A, Bammler TK, Govindarajan R, Hebert MF, Unadkat JD. Profiling gene expression in human placentae of different gestational age: an OPRV network and UW SCOR study. Reprod Sci 2008; 15:866-877.
7. Konkel L. Lasting impact of an ephemeral organ: the role of the placenta in fetal programming. Environ Health Perspect 2016; 124(7):A124- A129.
8. Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001; 42:1007-1017.
9. Gaccioli F, Lager S, Powell T, Jansson T. Placental transport in response to altered maternal nutrition. JDev Orig Health Dis 2013; 4(2):101-115.
10. Pettitt DJ, Nelso RG, Mf Saad, Bennett PH, Knowler WC. Diabetes and obesity in the offspring of pima indian woman with diabetes during pregnancy. Diabetes Care 1993; 16:310-314.
11. Prouillac C, Lecoeur S. The role of the placenta in fetal exposure to xenobiotics: importance of membrane transporters and human models for transfer studies. Drug Metab Dispos 2010; 38:1623-1635.
12. Barker DJP, Godfrey KM, Gluckman PD, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341:938-941.
13. Harder T, Rodekamp E, Schellong K, Dudenhausen JW, Plagemann A. Birth weight and subsequent risk of type 2 diabetes: a meta-analysis. Am J Epidemiol 2007; 165(8):849-857.
14. Mao Q. BCRP/ABCG2 in the placenta: expression, function and regulation. Pharm Res 2008; 25(6):1244-1255.
15. 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; 20:736-763.
16. Ceckova-Novotna M, Pavek P, Staud F. P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol 2006; 22:400-410.
17. Malek A, Obrist C, Wenzinger S, von Mandach U. The impact of cocaine and heroin on the placental transfer of methadone. Reprod Biol Endocrinol 2009; 7(61):61-70.
18. 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:R963-R969.
19. Gil S, Saura R, Forestier F, Farinotti R. P-glycoprotein expression of the human placenta during pregnancy. Placenta 2005; 26:268-270.
20. Sun M, Kingdom J, Baczyk D, Lye SJ, Matthews SG, Gibb W. Expression of the multidrug resistance P-glycoprotein, (ABCB1 glycoprotein) in the human placenta decreases with advancing gestation. Placenta 2006; 27:602-609.
21. Lye P, Bloise E, Dunk C, Javam M, Gibb W, Lye SJ, Matthews SG. Effect of oxygen on multidrug resistance in the first trimester human placenta. Placenta 2013; 34:817-823.
22. Kimura Y, Morita SY, Matsuo M, Ueda K. Mechanism of multidrug recognition by MDR1/ABCB1. Cancer Sci 2007; 98:1303-1310.
23. 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 2006; 290(5):R1357-R1365.
24. Patel P, Weerasekera N, Hitchins M, Boyd CAR, Johnston DG, Williamson C. Semi quantitative expression analysis of MDR3, FIC1, BSEP, OATP-A, OATP-C, OATP-D, OATP-E and NCTP gene transcripts in 1st and 3rd trimester human placenta. Placenta 2003; 24: 39-44.
25. Jacquemin E, Cresteil D, Manouvrier S, Boute O, Hadchouel M. Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. Lancet 1999; 353:210-211.
26. Borst P, Evers R, Kool M, Wijnholds J. A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 2000; 92:1295-1302.
27. Serrano MA, Macias RIR, Briz O, Monte MJ, Blazquez AG, Williamson C, Kubitz R, Marin JJG. 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; 28:107-117.
28. St-Pierre MV, Serrano MA, Macias RI, Dubs U, Hoechli M, Lauper U, Meier PJ, Marin JJ. Expression of members of the multidrug resistance protein family in human term placenta. Am J Physiol Regul Integr Comp Physiol 2000; 279:R1495-R1503.
29. Macias RI, Marin JJ, Serrano MA. Excretion of biliary compounds during intrauterine life. World J Gastroenterol 2009; 15:817-828.
30. Reider MJ. Prevention of neural tube defects with periconceptional folic acid. Clin Perinatol 1994; 21:483-503.
31. Pascolo L, Fernetti C, Pirulli D, Crovella S, Amoroso A, Tiribelli C. Effects of maturation on RNA transcription and protein expression on four MRP genes in human placenta and in BeWo cells. Biochem Biophys Res Commun 2003; 303:259-265.
32. Williams PJ, Mistry HD, Morgan L. Folate transporter expression decreases in the human placenta throughout pregnancy and in preeclampsia. Pregnancy Hypertens 2012; 2:123-131.
33. Sasaki K, Duan J, Murohara T, Ikeda H, Shintani S, Shimada T, Akita T, Egami K, Imaizumi T. Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation. J Am Coll Cardiol 2003; 42(2):364-372.
34. Meyerzu Schwabedissen HE, Jedlitschky G, Gratz M, Haenisch S, Linnemann K, Fusch C, Cascorbi I, Kroemer HK. Variable expression of MRP2 (ABCC2) in human placenta: influence of gestational age and cellular differentiation. Drug Metab Dispos 2005; 33(7):896-904.
35. Meyerzu SchwabedissenHE, Grube M, Heydrich B, Linnemann K, Fusch C, Kroemer HK, Jedlitschky G. Expression, localization and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation. Am J Pathol 2005; 166:39-48.
36. Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res 1998; 58:5337-5339.
37. Morrissey KM, Wen CC, Johns SJ, Zhang L, Huang SM, Giacomini KM. The UCSF-FDA TransPortal: a public drug transporter database. Clin Pharmacol Ther 2012; 92(5):545-546.
38. Evseenko DA, Murthi P, Paxton JW, Reid G, Emerald BS, Mohankumar KM, Lobie PE, Brennecke SP, Kalionis B, Keelan JA. The ABC transporter BCRP/ABCG2 is a placental survival factor, and its expression is reduced in idiopathic human fetal growth restriction. Faseb J 2007; 21:3592- 3605.
39. Sieppi E, Vahakangas K, Rautio A, Letta F, Paulesu L, Myllynen P. The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of the ABCG2 transporter protein in human term placental explant cultures. Mol Cell Endocrinol 2016; 429:41-49.
40. Yeboah D, Sun M, Kingdom J, Baczyk D, Lye SJ, Matthews SG, Gibb W. 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; 84:1251-1258.
41. Petrovic V, Kojovic D, Cressman A, Piquette-Miller M. Maternal bacterial infections impact expression of drug transporters in human placenta. Int Immunopharmacol 2015; 26(2):349-356.
42. Meyerzu Schwabedissen HE, Grube M, Dreisbach A, Jedlitschky G, Meissner K, Linnemann K, Fusch C, Ritter CA, Volker U, Kroemer HK. Epidermal growth factor-mediated activation of the map-kinase cascade results in altered expression and function of ABCG2 (BCRP). Drug Metab Dispos 2006; 34:524-533.
43. Sitras V, Fenton C, Paulssen R, Vartun A, Acharya G. Differences in gene expression between first and third trimester human placenta: a microarray study. PLoS One 2012; 7:e33294. doi: 10.1371/journal. pone.0033294. pmid:22442682.
44. He L, Vasiliou K, Nebert DW. Analysis and update of the human solute carrier (SLC) gene superfamily. Hum Genomics 2009; 3:195-205.
45. Roth M, Obaidat A, Hagenbuch B. OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 2012; 165:1260-1287.
46. Obaidat A, Roth M, Hagenbuch B. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. Annu Rev Pharmacol Toxicol 2012; 52:135-151.
47. Wang H, Yan Z, Dong M, Zhu X, Wang H, Wang Z. Alteration in placental expression of bile acids transporters OATP1A2, OATP1B1, OATP1B3 in intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet 2012; 285(6):1535-1540.
48. Phillips RJ, Fortier MA, Bernal AL. Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation. BMC Pregnancy Childbirth 2014; 14:241-255.
49. St-Pierre MV, Hagenbuch B, Ugele B, Meier PJ, Stallmach T. Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta. J Clin Endocrinol Metab 2002; 87(4):1856-1863.
50. Lofthouse EM, Brooks S, Cleal JK, Hanson MA, Poore KR, O'Kelly IM, Lewis RM. Glutamate recycling may drive organic anion transport on the basal membrane of human placental syncytiotrophoblast. J Physiol 2015; 593(20):4549-4559.
51. Sato K, Sugawara J, Sato T,Mizutamari H, Suzuki T, Ito A,Mikkaichi T, Onogawa T, Tanemoto M, Unno M, Abe T, Okamura K. Expression of organic anion transporting polypeptide E (OATP-E) in human placenta. Placenta 2003; 24(2-3):144-148.
52. Sata R, Ohtani H, TsujimotoM, Murakami H, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Nagata H, Tsukimori K, Nakano H, Sawada Y. Functional analysis of organic cation transporter 3 expressed in human placenta. J Pharm Exp Ther 2005; 315(2):888-895.
53. Grube M, Schwabedissen HM, Draber K, Prager D, Moritz KU, Linnemann K, Fusch C, Jedlitschky G, Kroemer HK. Expression, localization, and function of the carnitine transporter OCTN2 (SLC22A5) in a human placenta. Drug Metab Dispos 2005; 33:31-37.
54. Settle P, Mynett K, Speake P, Champion E, Doughty IM, Sibley CP, D'Souzs SW, Glazier J. Polarized lactate transporter activity and expression in the syncytiotrophoblast of the term human placenta. Placenta 2004; 25(6):469-504.
55. Ganapathy V, Prasad PD. Role of transporters in placental transfer of drugs. Toxicol Appl Pharmacol 2005; 207(2):381-387.
56. Hosoyamada M, Sekine T, Kanai Y, Endou H. Molecular cloning and functional expression of a multispecfic organic anion transporter from human kidney. Am J Physiol 1999; 276:F122-F128.
57. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H. Molecular cloning and characterisation of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem 2000; 275:4507-4512.
58. Ugele B, St-Pierre MV, Pihusch M, Bahn A, Hantschmann P. Characterisation and identification of steroid sulfate transporters of human placenta. Am J Physiol Endocrinol Metab 2003; 284:E390-E398.
59. Yasuda S, Hasui S, Kobayashi M, Itagaki S, Hirano T, Iseki K. The mechanism of carrier-mediated transport of folates in BeWo cells: the involvement of heme carrier protein 1 in placental folate transport. Biosci Biotechnol Biochem 2008; 72(2):329-334.
60. Rask-Andersen M, Marusam S, Fredriksson R, Schioth HB. Solute carriers as drug targets: current use, clinical trials and perspective. Mol Cell Ther 2014; 2(15):702-710.
61. Nigam SK. What do drug transporters really do? Nat Rev Drug Discov 2015; 14:29-44.
62. Tomi M, Eguchi H, Ozaki M, Tawara T, Nishimura S, Higuchi K, Maruyama T, Nishimura T, Nakashima E. Role of OAT4 in uptake of estriol precursor 16a-hydroxydehydroepiandrosterone sulfate into human placental syncytiotrophoblasts from fetus. Endocrinology 2015; 156(7):2704-2712.
63. Ahmadimoghaddam D, Hofman J, Zemankova L, Nachtigal P, Dolezelova E, Cerveny L, Ceckova M, Micuda S, Staud F. 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):471-481.
64. Ahmadimoghaddam D, Zemankova L, Nachtigal P, Dolezelova E, Neumanova Z, Cerveny L, Ceckova M, Kacerovsky M, Micuda S, Staud F. Organic cation transporter 3 (oct3/slc22a3) and multidrug and toxin extrusion (mate1/slc47a1) transporter in the placental and fetal tissues: expression profile and fetus protective role at different stages of gestation. Biol Reprod 2013; 88(3):55.
65. Loubiere LS, Vasilopoulou E, Bulmer JN, Taylor PM, Stieger b, Verrey F, McCabe CJ, Franklyn JA, Kilby MD, Chan SY. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction. Placenta 2010; 31:295-304.
66. Alzamil HA, Pawade J, Fortier MA, Bernal AL. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor. Front Physiol 2014; 5:272.
67. Schmidt A, Morales-Prieto DM, Pastuschek J, Frohlich K, Markert UR. Only humans have human placentas: molecular differences between mice and humans. J Reprod Immunol 2015; 108:65-71.
68. Beckman DA, Koszalka TR, Jensen M, Brent RL. Experimental manipulation of the rodent visceral yolk sac. Teratology 1990; 41:395-404.
69. Chu X, Bleasby K, Evers R. Species differences in drug transporters and implications for translating preclinical findings to humans. Expert Opin Drug Metab Toxicol 2013; 9(3):237-252.
70. Rossant J, Cross JC. Placental development: lessons from mousemutants. Nat Rev Genet 2001; 2:538-548.
71. Mayhew TM. Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal mass. J Anat 2006; 208(6):785- 794.
72. Jansson T, Powell TL.Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? Placenta 2006; 27:S91- S97.
73. Rodrigues RF, Carter AM, Ambrosio CES, dos Santos TC, MiglinoMA. The subplacenta of the red-rumped agouti (dasyprocta leporina L). Reprod Biol Endocrinol 2006; 4:31.
74. Schatten H. Animal Models and Human Reproduction: Cell and Molecular Approaches With Reference to Human Reproduction. New Jersey: John Wiley and Sons; 2017:79.
75. Barry JS, Anthony RV. The pregnant sheep as a model for human pregnancy. Theriogenology 2008; 69(1):55-67.
76. Burton GJ, Fowden AL, Thornburg KL. Placental origins of chronic disease. Physiol Rev 2016; 96:1509-1565.
77. Mathiesen L, Morck TA, Zuri G, AndersonMH, Pehrson C, Frederiksen M, Mose T, Rytting E, Poulsen MS, Nielsen JKS, Knudsen LE. Modelling of human transplacental transport as performed in Copenhagen Denmark. Basic Clin Pharmacol Toxicol 2014; 115:93-100.
78. Nanovskaya T, Nekhayeva I, Karunaratne N, Audus K, Hankins GDV, Ahmed MS. Role of P-glycoprotein in transplacental transfer of methadone. Biochem Pharmacol 2005; 69(12):1869-1878.
79. Pattillo RA, Gey GO. The establishment of a cell line of human hormonesynthesizing trophoblastic cells in vitro. Cancer Res 1968; 28:1231- 1236.
80. Clifton VL, Murphy VE.Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Placenta 2004; 25:S45-S52.
81. Vyhlidal CA, Riffel AK, Haley KJ, Sharma S, Dai H, Tantisira KG,Weiss ST, Leeder JS. Cotinine in human placenta predicts induction of gene expression in fetal tissues. Drug Metab Dispos 2013; 41(2):305-311.
82. Niu Z, Xie C, Wen X, Tian F, Ding P, He Y, Lin J, Yuan S, Guo X, Jia, D, Chen WQ. Placenta mediates the association between maternal second hand smoke exposure during pregnancy and small for gestational age. Placenta 2015; 36:876-880.
83. Buckberry S, Bianco-Miotto T, Bent SJ, Dekker GA, Roberts CT. Integrative transcriptome meta-analysis reveals wide-spread sex-biased gene expression at the human fetal-maternal interface. Mol Hum Reprod 2014; 20(8):810-819.
84. Barker DJ. The origins of the developmental origins theory. J InternMed 2007; 261(5):412-417.
85. Van Abeelen AF, de Rooij SR, Osmond C, Painter RC, Veenendaal MV, Bossuyt PM, Elias SG, Grobbee DE, van der Schouw YT, Barker DJ, Roseboom TJ. The sex-specific effects of famine on the association between placental size and later hypertension. Placenta 2011; 32:694-698.
86. Lubchencho LO, Hansman C, Dressler M, Boyd E. Intrauterine growth as estimated from live born birth-weight data at 24 to 42 weeks of gestation. Pediatrics 1963; 32:793-800.
87. Vore M, Leggas M. Progesterone acts via progesterone receptors A and B to regulate breast cancer resistance protein expression. Mol Pharmacol 2008; 73(3):613-615.
88. Fornes R, Hu M, Maliqueo M, Kokosar M, Benrick A, Carr D, Billig H, Jansson T, Manni L, Stener-Victorin E. Maternal testosterone and placental function: effect of electroacupuncture on placental expression of angiogenic markers and fetal growth. Mol Cell Endocrinol 2016; 433:1-11.
89. Cleal JK, Day PL, Hanson MA, Lewis RM. Sex differences in the mRNA levels of housekeeping genes in human placenta. Placenta 2010; 31(6):556-557.
90. Parisi MA, Spong CY, Zajicek A, Guttmacher AE. We don't know what we don't study: the case for research on medication effects in pregnancy. Am J Med Genet C Semin Med Genet 2011; 157(3):247-250.
91. Shields KE, Lyerly AD. Exclusion of pregnant woman from industrysponsored clinical trials. Obstet Gynecol 2013; 122:1077-1081.
92. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet 2004; 43(8):487-514.
93. Munic V, Kelneric Z, Mikac L, Erakovic Haber V. Differences in assessment of macrolide interaction with human MDR1 (ABCB1, P-gp) using rhodamine-123 efflux, ATPase activity and cellular accumulation assays. Eur J Pharm Sci 2010; 41:86-95.
94. Audette MC, Challis JRG, Jones RL, Sibley CP, Matthews SG. Synthetic glucocorticoid reduces human placental system a transport in woman treated with antenatal therapy. J Clin Endocrinol Metab 2014; 99(11):E2226-E2233.
95. Murphy KE, Hannah ME, Willian AR, Hewson SA, Ohlsson A, Kelly EN, Matthews SG, Saigal S, Asztalos E, Ross S, Delisle MF, Amankwah K et al. Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial. Lancet 2008; 372: 2143-2151.
96. Merino G, Jonker JW, Wagenaar E, van Herwaarden AE, Schinkel AH. The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol Pharmacol 2005; 67:1758-1764.
97. Fisher BG, Thankamony A, Hughes IA, Ong KK, Dunger DB, Acerini CL. Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants. Hum Reprod 2016; (in press). Published online ahead of print 8 Sept 2016; DOI 10.1093/humrep/dew196.
98. Blazquez AG, Briz O, Gonzalez-Sanchez E, PerezMJ, Ghanem CI, Marin JJ. 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.
99. Albrecht C, Soumain S, Tetlow N, Patel P, Sullivan MHF, Lakasing L, Nicolaides K, Williamson C. Placental ABCA1 expression is reduced in primary antiphospholipid syndrome compared to pre-eclampsia and controls. Placenta 2007; 28:701-708.
100. Aye IL, Waddell BJ, Mark PJ, Keelan JA. Placental ABCA1 and ABCG1 transporters efflux cholesterol and protect trophoblasts from oxysterol induced toxicity. Biochim Biophys Acta 2010; 1801(9):1013-1024.
101. Bloise E, Ortiga-Carvalho TM, Reis FM, Lye SJ, Gibb W, Matthews SG. ATP-binding cassette transporters in reproduction: a new frontier. Hum Reprod Update 2016; 22(2):164-181.
102. Azzaroli F, Mennone A, Feletti V, Simoni P, Baglivo E, Montagnani M, Rizzo N, Pelusi G, DE Aloysio D, Lodato F, Festi D, Colecchia A et al. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid. Aliment Pharmacol Ther 2007; 26:1139-1146.
103. Marin JJG, Macias RIR, Briz O, Perez MJ, Blazquez AG, Arrese M, Serrano MA. Molecular bases of the fetal-placenta-maternal liver excretory pathway for cholephilic compounds. Liver Int 2008; 28(4): 435-454.
104. Faller DP, Egan DA, Ryan MP. Evidence for location of the CFTR in human placental apical membrane vesicles. Am J Physiol 1995; 269(1):C148-C155.
105. Litman T, Jensen U, Hansen A, Covitz KM, Zhan Z, Fetsch P, Abati Am Hansen PR, Horn T, Skovsgaard T, Bates SE. Use of peptide antibodies to probe for the mitoxantrone resistance-associated protein MXR/BCRP/ABCP/ABCG2. Biochim Biophys Acta 2002; 1565:6-16.