Placental drug transporters and their role in fetal protection

Iqbal, Majid; Audette, Melanie C.; Petropoulos, Sophie; Gibb, William; Matthews, Stephen G.

doi:10.1016/j.placenta.2012.01.008

Cited by 117 publications

(99 citation statements)

References 82 publications

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“…BCRP is highly expressed in the apical membrane of the syncytiotrophoblast [8, 48-50], and the up-regulation may promote increased efflux of BCRP substrates. Therefore, third-trimester chorioamnionitis has the potential to decrease accumulation of BCRP endogenous and exogenous substrates in the fetal compartment including folate, antibiotics and antiretrovirals.…”

Section: Discussionmentioning

confidence: 99%

Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta

Império

Bloise

Javam³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The ATP-binding cassette (ABC) transporters mediate drug biodisposition and immunological responses in the placental barrier. In vitro infective challenges alter expression of specific placental ABC transporters. We hypothesized that chorioamnionitis induces a distinct pattern of ABC transporter expression. Methods: Gene expression of 50 ABC transporters was assessed using TaqMan® Human ABC Transporter Array, in preterm human placentas without (PTD; n=6) or with histological chorioamnionitis (PTDC; n=6). Validation was performed using qPCR, immunohistochemistry and Western blot. MicroRNAs known to regulate P-glycoprotein (P-gp) were examined by qPCR. Results: Up-regulation of ABCB9, ABCC2 and ABCF2 mRNA was detected in chorioamnionitis (p<0.05), whereas placental ABCB1 (P-gp; p=0.051) and ABCG2 (breast cancer resistance protein-BCRP) mRNA levels (p=0.055) approached near significant up-regulation. In most cases, the magnitude of the effect significantly correlated to the severity of inflammation. Upon validation, increased placental ABCB1 and ABCG2 mRNA levels (p<0.05) were observed. At the level of immunohistochemistry, while BCRP was increased (p<0.05), P-gp staining intensity was significantly decreased (p<0.05) in PTDC. miR-331-5p, involved in P-gp suppression, was upregulated in PTDC (p<0.01) and correlated to the grade of chorioamnionitis (p<0.01). Conclusions: Alterations in the expression of ABC transporters will likely lead to modified transport of clinically relevant compounds at the inflamed placenta. A better understanding of the potential role of these transporters in the events surrounding PTD may also enable new strategies to be developed for prevention and treatment of PTD.

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Section: Discussionmentioning

confidence: 99%

Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta

Império

Bloise

Javam³

et al. 2018

Cell Physiol Biochem

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“…The fetal placenta consists of syncytiotrophoblast and cytotrophoblast layers. The BCRP is located in the maternalfacing apical membrane of the syncytiotrophoblast and the fetal blood vessels of the villous core, both of which are of fetal origin (Weier et al, 2008;Prouillac and Lecoeur, 2010;Mason et al, 2011;Ni and Mao, 2011;Iqbal et al, 2012;Staud et al, 2012). Therefore, only the genotypes of 421C > A and 34G > A polymorphisms in the ABCG2 gene of the children (but not mothers) might be associated with altered BCRP expression and transport activity in placenta, thereby modifying the inter-individual susceptibility to CHDs.…”

Section: Study Participantsmentioning

confidence: 99%

“…The placenta is obviously considered the crucial organ responsible for successful ontogeny. Evidence strongly suggests that the placenta expresses a range of transporters which are capable of controlling the transplacental dispositions of many toxicant agents, thereby playing a crucial role in fetal protection against maternal toxins (Myllynen et al, 2005Ceckova et al, 2006;Atkinson et al, 2007;Behravan and Piquette-Miller, 2007;Myren et al, 2007;Vahakangas and Myllynen, 2009;Prouillac and Lecoeur, 2010;Ni and Mao, 2011;Iqbal et al, 2012). Of main interest are the ATPbinding cassette (ABC) transporters, particularly the P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP), which are most intensively studied currently.…”

Section: Introductionmentioning

confidence: 99%

Associations Between ABCG2 Gene Polymorphisms and Isolated Septal Defects in a Han Chinese Population

Wang

Xie

et al. 2014

DNA and Cell Biology

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Breast cancer resistance protein (BCRP) in the placenta, encoded by the ABCG2 gene in humans, plays an essential role in regulating fetal exposure to toxicants and the maintenance of cellular folic acid homeostasis. This study aimed at exploring the associations between 421C > A and 34G > A polymorphisms within the ABCG2 gene of the children and isolated septal defects in a Han Chinese population. An age-and gendermatched case-control study involving 210 pairs was conducted. Genotyping of the ABCG2 gene polymorphisms was performed by sequencing. Forty-six placental tissues and umbilical cords from healthy Han Chinese mothers with uncomplicated pregnancy were collected to investigate the impact of these two polymorphisms on the transcription and translation activities of the ABCG2 gene. The results showed that there were no differences in the genotype distributions and allele frequencies of 421C > A polymorphism. For the 34G > A polymorphism, more cases were carriers of the GA/AA genotypes (adjusted odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.0-2.3). The ABCG2 mRNA and protein expression did not differ among the three genotypes of 421C > A polymorphism. For the 34G > A polymorphism, the ABCG2 mRNA and protein expression of the GG genotype was significantly higher than that of the AA genotype. In conclusion, 34G > A polymorphism in the ABCG2 gene of the children is associated with isolated septal defects in a Han Chinese population, presumably through regulation of BCRP expression in the placenta.

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“…SSRIs administered during pregnancy will initially enter the maternal blood stream before passing through the placenta and into the blood stream of the fetus (Iqbal et al 2012). This transfer may cause an imbalance in fetal neurotransmission, which in turn may alter neural programming, plasticity, structural, and functional development (Gaspar et al 2003;).…”

Section: Introductionmentioning

confidence: 99%

Behavior and inhibitory control in children with prenatal exposure to antidepressants and medically untreated depression

et al. 2016

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Analyses of variance revealed no effects of prenatal exposure to depression or SSRIs upon general cognition or inhibition. Regarding behavioral problems, there was a significant negative association between both SSRI and depression exposure upon externalizing, and between SSRI exposure and internalizing problems. The results are interpreted in light of theories on interactive specialization and reactivity.

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Placental drug transporters and their role in fetal protection

Cited by 117 publications

References 82 publications

Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta

Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta

Associations Between ABCG2 Gene Polymorphisms and Isolated Septal Defects in a Han Chinese Population

Behavior and inhibitory control in children with prenatal exposure to antidepressants and medically untreated depression

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