Expression of the Multidrug Resistance P-Glycoprotein, (ABCB1 glycoprotein) in the Human Placenta Decreases with Advancing Gestation

Sun, Mingjun; Kingdom, John; Baczyk, Dora; Lye, Stephen J.; Matthews, Stephen G.; Gibb, William

doi:10.1016/j.placenta.2005.05.007

Cited by 203 publications

(158 citation statements)

References 36 publications

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“…1, A and B). Other laboratories have shown that MDR1 expression is not dependent on the region of the sample or on cesarean versus vaginal delivery (Camus et al, 2006;Sun et al, 2006). MRP1, MRP2, and MDR3 were present in all samples, but their expression was variable and did not appear to be dramatically affected by pregnancy condition (Fig.…”

Section: Resultsmentioning

confidence: 74%

“…The general consensus is that MDR1 and BCRP expression decline (Gil et al, 2005;Mathias et al, 2005;Sun et al, 2006;Meyer zu Schwabedissen et al, 2006), whereas MRP2 and MDR3 levels increase with gestational age toward term (Patel et al, 2003;Meyer zu Schwabedissen et al, 2005). These changes may reflect a physiological adaptation to the changing requirements for fetal protection, especially in the preterm period.…”

Section: Discussionmentioning

confidence: 99%

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ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Mason

Buhimschi²,

Buhimschi³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Fetal drug exposure is determined by the type and concentration of placental transporters, and their regulation is central to the development of new treatments and delivery strategies for pregnant women and their fetuses. We tested the expression of several clinically important transporters in the human placenta associated with various pregnancy conditions (i.e., labor, preeclampsia, and preterm labor-inflammation). Placentas were obtained from five groups of women at the time of primary cesarean section: 1) term no labor; 2) term labor; 3) preterm no labor (delivered for severe preeclampsia); 4) preterm labor without inflammation (PTLNI); and 5) preterm labor with inflammation (PTLI). Samples were analyzed by Western blot and immunohistochemistry to identify changes in protein expression. Relative mRNA expression was determined by quantitative real-time polymerase chain reaction. A functional genomic approach was used to identify placental gene expression and elucidate molecular events that underlie the given condition. Placental expression of ATP-binding cassette transporters from women in labor and women with preeclampsia was unaltered. Multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) and mRNA expression increased in placentas of women with preterm labor with inflammation. Molecular pathways of genes up-regulated in PTLI samples included cytokinecytokine receptor interactions and inflammatory response compared with those in the PTLNI group. The mRNA expression of MDR1 and BCRP was correlated with that of interleukin-8, which also increased significantly in PTLI samples. These data suggest that the transfer of drugs across the placenta may be altered in preterm pregnancy conditions associated with inflammation through changes in MDR1 and BCRP.

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Section: Resultsmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Mason

Buhimschi²,

Buhimschi³

et al. 2011

Drug Metab Dispos

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“…Interestingly, the mean expression of ABCB1 has been found to be two times higher in the early (13-14 week) compared with the late (full-term) gestation human placenta, which is mostly fetal in origin. [17][18][19] We observed significant association with ABCB1 SNPs rs1128503, rs2032582, and rs1045642, although only rs1128503 remained significant after Bonferroni correction. It should be noted, however, that SNPs, rs1128503, rs2032582, and rs1045642, are not independent but are in strong linkage disequilibrium, 14 therefore application of …”

Section: Discussionmentioning

confidence: 74%

“…The ABCtransporter proteins ABCB1, ABCC1, ABCC2, and ABCG2 are known to be expressed in maternal barrier organs (intestine, kidney, liver, lung) and the fetal barrier organ (placenta). ABCB1 is highly expressed in human placenta during early gestation, [17][18][19] while ABCG2 is expressed more in mid gestation. 20 During late gestation, ABCC1 21 and ABCC2 22 show the highest placental expression.…”

Section: Discussionmentioning

confidence: 99%

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

et al. 2013

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ATP-binding cassette (ABC) proteins in the placenta regulate fetal exposure to xenobiotics. We hypothesized that functional polymorphisms in ABC genes influence risk for non-syndromic oral clefts (NSOC). Both family-based and case-control studies were undertaken to evaluate the association of nine potentially functional single-nucleotide polymorphisms within four ABC genes with risk of NSOC. Peripheral blood DNA from a total of 150 NSOC case-parent trios from Singapore and Taiwan were genotyped, as was cord blood DNA from 189 normal Chinese neonates used as controls. In trios, significant association was observed between the ABCB1 single-nucleotide polymorphisms and NSOC (Po0.05). Only ABCB1 rs1128503 retained significant association after Bonferroni correction (odds ratio (OR) ¼ 2.04; 95% confidence interval (CI) ¼ 1.42-2.98), while rs2032582 and rs1045642 showed nominal significance. Association with rs1128503 was replicated in a case-control analysis comparing NSOC probands with controls (OR ¼ 1.58; 95% CI ¼ 1.12-2.23). A comparison between the mothers of probands and controls showed no evidence of association, suggesting NSOC risk is determined by fetal and not maternal ABCB1 genotype. The two studies produced a combined OR of 1.79 (95% CI ¼ 1.38-2.30). The T-allele at rs1128503 was associated with higher risk. This study thus provides evidence that potentially functional polymorphisms in fetal ABCB1 modulate risk for NSOC, presumably through suboptimal exclusion of xenobiotics at the fetal-maternal interface.

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“…It is now well established that P-gp is expressed by the placental syncytiotrophoblast throughout gestation (38) and that at term it is localized to the microvillous maternal facing plasma membrane (Figs. 1A and 2) (8,39).…”

Section: Placental Mdrpsmentioning

confidence: 99%

Antiepileptic Medication During Pregnancy: Does Fetal Genotype Affect Outcome?

2007

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Expression of the Multidrug Resistance P-Glycoprotein, (ABCB1 glycoprotein) in the Human Placenta Decreases with Advancing Gestation

Cited by 203 publications

References 36 publications

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

Antiepileptic Medication During Pregnancy: Does Fetal Genotype Affect Outcome?

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