Evidence map›Paper›PMID 28638048›Full record

ArticleScientific reports2017

Maternal folate deficiency causes inhibition of mTOR signaling, down-regulation of placental amino acid transporters and fetal growth restriction in mice.

Fredrick J Rosario, Peter W Nathanielsz, Theresa L Powell, Thomas Jansson

Abstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Fredrick J RosarioDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. fredrick.joseph@ucdenver.edu.
Peter W NathanielszDepartment of Animal Science, University of Wyoming, Laramsie, WY, 82071, USA.
Theresa L PowellDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Thomas JanssonDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

Funding

The Southwest National Primate Research Center Supplement- Infrastructure improvements of ABSL2 holding areasP51OD011133 · OD · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI Larry S. Schlesinger · 2012 to 2026
$129.7M
PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Wendy M Kohrt · 1995 to 2026
$32.6M
Trophoblast mTOR: a critical hub linking maternal nutrient supply to placental function, fetal growth and fetal islet functionR01HD068370 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JANSSON, THOMAS, ROSARIO-JOSEPH, FREDRICK · 2011 to 2024
$4.1M
mTOR as a trophoblast folate sensorR01HD078376 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JANSSON, THOMAS · 2014 to 2018
$1.6M
NICHD NIH HHS R01 HD078376NIDDK NIH HHS P30 DK048520NIH HHS P51 OD011133
6 · The paper itself

Abstract

Maternal folate deficiency is linked to restricted fetal growth, however the underlying mechanisms remain to be established. Here we tested the hypothesis that mTOR functions as a folate sensor in vivo in mice and that maternal folate deficiency inhibits placental mTOR signaling and amino acid transporter activity and causes fetal growth restriction. Folate deficient mice had lower serum folate (-60%). In late pregnancy, fetal weight in the folate deficient group was decreased (-17%, p < 0.05), whereas placental weight, litter size and crown rump length were unaltered. Maternal folate deficiency inhibited placental mTORC1 and mTORC2 signaling and decreased trophoblast plasma membrane System A and L amino acid transporter activities and transporter isoform expression. Folate deficiency also caused a decrease in phosphorylation of specific functional readouts of mTORC1 and mTORC2 signaling in multiple maternal and fetal tissues. We have identified a novel specific molecular link between maternal folate availability and fetal growth, involving regulation of placental mTOR signaling by folate, resulting in changes in placental nutrient transport. mTOR folate sensing may have broad biological significance because of the critical role of folate in normal cell function and the wide range of disorders, including cancer, that have been linked to folate availability.

Indexed as

Amino Acid Transport SystemsAnimalsDown-RegulationFemaleFetal Growth RetardationFolic AcidFolic Acid DeficiencyLysosomal-Associated Membrane Protein 2Maternal Nutritional Physiological PhenomenaMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mice, Inbred ICRPapioPlacentaPlacentationPregnancyAmino Acid Transport SystemsFolic AcidLysosomal-Associated Membrane Protein 2Mechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2mTOR protein, mouseTOR Serine-Threonine Kinases

Identifiers

PMID28638048
PMCPMC5479823

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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.