Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia

Rahat, Beenish; Hamid, Abid; Bagga, Rashmi; Kaur, Jyotdeep

doi:10.3389/fnut.2022.847136

Cited by 18 publications

(21 citation statements)

References 51 publications

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“…Folic acid is prescribed to pregnant women to prevent fetal defects and to enhance migration and invasion functions of EVTs during placentation [1, 12,47]. We show here, for the first time, that palmitic acid causes folate efflux from EVTs with a direct correlation between the rate of efflux and the time of exposure to this saturated fatty acid.…”

Section: Discussionmentioning

confidence: 62%

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.

show abstract

Section: Discussionmentioning

confidence: 62%

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

Ashar¹,

Teng²,

Wurpel³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Folic acid is prescribed to pregnant women to prevent fetal defects and to enhance migration and invasion functions of EVTs during placentation [ 1 , 12 , 45 ]. We show here, for the first time, that palmitic acid causes folate efflux from EVTs with a direct correlation between the rate of efflux and the time of exposure to this saturated fatty acid.…”

Section: Discussionmentioning

confidence: 99%

“…ABC transporters are also present in the EVTs, which express ABCA1, ABCA5, and ABCC1/MRP1 [ 10 , 11 ]. Folic acid, which is required for normal migration and invasion of EVTs [ 12 ], is a major substrate of MRP1 [ 7 ].…”

Section: Introductionmentioning

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.

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“…There are so much similarities between trophoblast cells into the maternal uterus and the growth of cancer cells ( 32 ). In addition, the development of placental involves a complex but strict gene regulation ( 33 ). The placenta, therefore, act as a pseudomalignant tissue.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa-circ-0005238 enhances trophoblast migration, invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis

et al. 2022

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BackgroundFetal growth restriction (FGR) is attributed to various maternal, fetal, and placental factors. Trophoblasts participate in the establishment and maintenance of pregnancy from implantation and placentation to providing nutrition to fetus. Studies have reported that impaired trophoblast invasion and proliferation are among factors driving development of FGR. Circular RNAs (circRNAs) can regulate trophoblast function. We assessed the significance of circRNAs underlying FGR development.Materials and methodsNext generation sequencing (NGS) was carried out to quantify levels of circRNAs in placenta tissues with and without FGR. In vitro experiments including transfection, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) assays, flow cytometry analyses, Transwell assays, wound healing assays, western blotting, qRT-PCR, dual-luciferase assays, immunofluorescence staining, and RIP assay were performed.ResultsThere were 18 differentially expressed circRNAs between FGR placentas and uncomplicated pregnancies, while levels of hsa-circ-0005238 were markedly low in FGR placentas. Our in vitro experiments further revealed that hsa-circ-0005238 suppressed apoptosis and enhanced proliferation, migration, invasion of trophoblast cell lines. The hsa-miR-370-3p was identified as a direct target of hsa-circ-0005238. Mechanistically, hsa-miR-370-3p prevents invasion as well as migration of trophoblast cells by downregulating CDC25B.ConclusionThe hsa-circ-0005238 modulates FGR pathogenesis by inhibiting trophoblast cell invasion and migration through sponging hsa-miR-370-3p. Hence, targeting this circRNA may be an attractive strategy for FGR treatment.

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Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia

Cited by 18 publications

References 51 publications

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

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

Circular RNA hsa-circ-0005238 enhances trophoblast migration, invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis

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