Overview of Drug Transporters in Human Placenta

Yamashita, Michiko; Markert, Udo R.

doi:10.3390/ijms222313149

Cited by 16 publications

(18 citation statements)

References 110 publications

(80 reference statements)

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“…It is well-known that alterations in the expression of these transporters during different stages of gestation or due to ABC transporter modulators can lead to changes in the transfer of substrates to and from the fetus [ 9 , 36 , 37 ]. However, there are limited reports about the function and presence of ABC transporters in extravillous trophoblasts [ 8 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Ashar

Teng²,

Wurpel³

et al. 2022

Biomolecules

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Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetylcysteine (NAC) prevented the palmitic acid-mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in utero environment.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Ashar

Teng²,

Wurpel³

et al. 2022

Biomolecules

View full text Add to dashboard Cite

show abstract

“…It is well known that alterations in the expression of these transporters during different stages of gestation or due to ABC transporter modulators can lead to changes in the transfer of substrates to and from the fetus [9,37,38]. However, there are limited reports about the function and presence of ABC transporters in extravillous trophoblasts [8,39].…”

Section: Discussionmentioning

confidence: 99%

Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Ashar¹,

Teng²,

Wurpel³

et al. 2022

Preprint

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Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetyl cysteine (NAC) prevented the palmitic acid mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in-utero environment.

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“…Thus, the placental barrier protects the developing fetus and later embryo from toxicants and xenobiotics, and it ensures its proper development. The placenta is the largest fetal organ, and its main components include the chorionic villi and the fetal vascular endothelium [ 24 , 25 ]. In detail, shortly after implantation of the blastocyst, the placenta starts to develop, subsequently differentiating into trophoblasts.…”

Section: Histological and Transport Characteristicsmentioning

confidence: 99%

“…One of the histological features of placental development is that the layer of cytotrophoblasts becomes discontinuous and that a thinning of the syncytiotrophoblast layer occurs. Permeability and transport properties of placenta, particularly of the syncytiotrophoblast layer, are important in regulating uptake and excretion of nutrients, hormones, and wastes, as well as in the protection from potential harmful xenobiotics [ 24 , 25 ]. Indeed, several key drug transporters are highly expressed in syncytiotrophoblasts and are believed to play a decisive role in controlling fetal exposure to endogenous and exogenous substances.…”

Section: Histological and Transport Characteristicsmentioning

confidence: 99%

Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta

et al. 2022

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Drug transporters play an important role in the maintenance of chemical balance and homeostasis in different tissues. In addition to their physiological functions, they are crucial for the absorption, distribution, and elimination of many clinically important drugs, thereby impacting therapeutic efficacy and toxicity. Increasing evidence has demonstrated that infectious, metabolic, inflammatory, and neurodegenerative diseases alter the expression and function of drug transporters. However, the current knowledge on transporter regulation in critical protective barriers, such as the brain and placenta, is still limited and requires more research. For instance, while many studies have examined P-glycoprotein, it is evident that research on the regulation of highly expressed transporters in the blood–brain barrier and blood–placental barrier are lacking. The aim of this review is to summarize the currently available literature in order to better understand transporter regulation in these critical barriers.

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Overview of Drug Transporters in Human Placenta

Cited by 16 publications

References 110 publications

RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta

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