The Significance of ABC Transporters in Human Placenta for the Exposure of Fetus to Xenobiotics

Karttunen, Vesa; Mohammed, Ali Mustafa; Vähäkangas, Kirsi

doi:10.1016/b978-0-12-804239-7.00067-6

Cited by 8 publications

(7 citation statements)

References 218 publications

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“…Various ABC transporters have been identified in the placenta and their localization and function at the maternal–fetal interface across gestation has been studied [ 35 ]. 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

“…Various ABC transporters have been identified in the placenta and their localization and function at the maternal-fetal interface across gestation has been studied [36]. 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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“…Compounds in the tobacco smoke, such as benzo(a)pyrene ( Karttunen et al, 2010 ) and nicotine ( Veid et al, 2011 ), as well as ethanol ( Veid et al 2011 ) go easily through human placenta and may be toxic in placental tissue (for a review, see Karttunen et al, 2017 ). In a recent review about the toxic effects of nicotine ( Suter and Aagaard, 2020 ) the authors point out that “no amount of nicotine is known to be safe in pregnancy”.…”

Section: Resultsmentioning

confidence: 99%

The effect of ethanol and nicotine on ER stress in human placental villous explants

Huovinen

Ietta

Repo

et al. 2022

Current Research in Toxicology

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The Significance of ABC Transporters in Human Placenta for the Exposure of Fetus to Xenobiotics

Cited by 8 publications

References 218 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

The effect of ethanol and nicotine on ER stress in human placental villous explants

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