ArticleScientific reports2016
Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Maternal Diet Quality Is Associated with Placental Proteins in the Placental Insulin/Growth Factor, Environmental Stress, Inflammation, and mTOR Signaling Pathways: The Healthy Start ECHO Cohort.The Journal of nutrition · 2022Trial
- Maternal lifestyle risk factors and human embryonic morphologic development using 3D ultrasound: a population-based prospective cohort study.Human reproduction (Oxford, England) · 2026Article
- Metabolic Reprogramming at the Maternal-Fetal Interface: Insights from Decidual Stromal Cells and Trophoblasts in Healthy Pregnancy Versus Recurrent Pregnancy Loss.International journal of molecular sciences · 2026Review
- Inducible trophoblast-specific knockdown of mechanistic target of rapamycin impairs placental folate transport in mice.The Journal of nutritional biochemistry · 2026Article
- mTOR Signaling Pathway in Antiphospholipid Syndrome: Pathogenesis and Potential Therapeutic Targets.Drug design, development and therapy · 2026Review
- Trophoblast-specific Deptor knockdown enhances trophoblast nutrient transport and fetal growth in mice.Acta physiologica (Oxford, England) · 2025Article
- Prenatal alcohol exposure is associated with altered feto-placental blood flow and sex-specific placental changes.JCI insight · 2025Article
- Establishment and comparison of human term placenta-derived trophoblast cells†.Biology of reproduction · 2024Article
- Endocytosis at the maternal-fetal interface: balancing nutrient transport and pathogen defense.Frontiers in immunology · 2024Review
- Oleic acid stimulation of amino acid uptake in primary human trophoblast cells is mediated by phosphatidic acid and mTOR signaling.FASEB bioAdvances · 2024Article
- Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.Nutrients · 2023Review
- Maternal-fetal cross-talk via the placenta: influence on offspring development and metabolism.Development (Cambridge, England) · 2023Review
- Placental Remote Control of Fetal Metabolism: Trophoblast mTOR Signaling Regulates Liver IGFBP-1 Phosphorylation and IGF-1 Bioavailability.International journal of molecular sciences · 2023Article
- Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.Advances in nutrition (Bethesda, Md.) · 2022Article
- Tadalafil Treatment of Mice with Fetal Growth Restriction and Preeclampsia Improves Placental mTOR Signaling.International journal of molecular sciences · 2022Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Placental Function and the Development of Fetal Overgrowth and Fetal Growth Restriction.Obstetrics and gynecology clinics of North America · 2021Review
- Interaction between Metformin, Folate and Vitamin BInternational journal of molecular sciences · 2021Review
- Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Folate deficiency in fetal life is strongly associated with structural malformations and linked to intrauterine growth restriction. In addition, limited availability of methyl donors, such as folate, during pregnancy may result in abnormal gene methylation patterns and contribute to developmental programming. The fetus is dependent on placental transfer of folate, however the molecular mechanisms regulating placental folate transport are unknown. We used cultured primary human trophoblast cells to test the hypothesis that mechanistic target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate folate transport by post-translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal folate uptake. Folate uptake stimulated by insulin + IGF-1 was mediated by mTORC2 but did not involve mTORC1. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of FR-α and RFC transporter isoforms without affecting global protein expression. Inhibition of the ubiquitin ligase Nedd4-2 had no effect on folate transport. In conclusion, we report for the first time that mTORC1/C2 are positive regulators of cellular folate uptake by modulating the cell surface abundance of specific transporter isoforms. We propose that regulation of placental folate transport by mTOR signaling provide a direct link between placental function, gene methylation and fetal programming.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.