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

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 u...

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Main Authors: Yunali Ashar, Qiuxu Teng, John N. D. Wurpel, Zhe-Sheng Chen, Sandra E. Reznik
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/12/8/1162
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author Yunali Ashar
Qiuxu Teng
John N. D. Wurpel
Zhe-Sheng Chen
Sandra E. Reznik
author_facet Yunali Ashar
Qiuxu Teng
John N. D. Wurpel
Zhe-Sheng Chen
Sandra E. Reznik
author_sort Yunali Ashar
collection DOAJ
description 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 <i>ABCC1</i> 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 <i>ABCC1</i> 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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spelling doaj-art-8f6a51a80a864b6a82503d134ef346702025-02-10T09:19:00ZengMDPI AGBiomolecules2218-273X2022-08-01128116210.3390/biom12081162RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and FunctionYunali Ashar0Qiuxu Teng1John N. D. Wurpel2Zhe-Sheng Chen3Sandra E. Reznik4Department of Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USADepartment of Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USADepartment of Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USADepartment of Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USADepartment of Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USANormal 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 <i>ABCC1</i> 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 <i>ABCC1</i> 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.https://www.mdpi.com/2218-273X/12/8/1162extravillous trophoblastplacentasaturated fatty acidin utero environmentMRP1
spellingShingle Yunali Ashar
Qiuxu Teng
John N. D. Wurpel
Zhe-Sheng Chen
Sandra E. Reznik
RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
Biomolecules
extravillous trophoblast
placenta
saturated fatty acid
in utero environment
MRP1
title RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
title_full RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
title_fullStr RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
title_full_unstemmed RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
title_short RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function
title_sort retracted palmitic acid impedes extravillous trophoblast activity by increasing mrp1 expression and function
topic extravillous trophoblast
placenta
saturated fatty acid
in utero environment
MRP1
url https://www.mdpi.com/2218-273X/12/8/1162
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