Evidence mapPaperPMID 41444682Full record

ArticleClinical epigenetics2025

Folic acid ameliorates placental structure and function in fetal growth restriction via epigenetic modifications.

Juanmei Gao, Yingya Lou, Weiwu He, Kaixing Xu, Xin Zhan, Jinyi Tong, Hongbo Zhai

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

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4 · The record

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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

7 authors.

Juanmei GaoKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Obstetrics, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, 310006, Zhejiang, China. 11807103@zju.edu.cn.
Yingya LouThe Fourth Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, Zhejiang, China.
Weiwu HeThe Fourth Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, Zhejiang, China.
Kaixing XuMedicine College of Hangzhou Normal University, Hangzhou, Zhejiang, China.
Xin ZhanKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Obstetrics, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, 310006, Zhejiang, China.
Jinyi TongKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Obstetrics, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, 310006, Zhejiang, China. tongjinyi@hospital.westlake.edu.cn.
Hongbo ZhaiKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Obstetrics, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, 310006, Zhejiang, China. zhaihb@126.com.

Funding

The Construction Fund of Key Medical Disciplines of Hangzhou NO. 2025HZZD07The Hangzhou Biomedical and Health Industry Development Support Science and Technology Special Project No. 2021WJCY098The Zhejiang Medical and Health Science and Technology Project No. 2022KY955
6 · The paper itself

Abstract

backgroundFetal growth restriction (FGR) is associated with perinatal complications and potential neurodevelopmental risks, yet mechanistic understanding of metabolic dysregulation remains incomplete. We investigated amniotic fluid metabolites as potential functional biomarkers of fetal-placental dysfunction and explored the possibility of folic acid-mediated epigenetic remediation of metabolic imbalances in FGR.

resultsIn FGR amniotic fluid, hypoxanthine was significantly upregulated, valproic acid (VPA) was significantly downregulated, and arginine/proline metabolism pathways were markedly enriched. Folic acid intervention significantly improved fetal growth parameters (crown-rump length, body weight, and placental weight; all P < 0.001). Compensatory labyrinth zone (Lb) hyperplasia was observed in FGR placenta, with a 40% increase in Lb/Jz ratio, while folic acid supplementation reduced Lb proportion by 10% and appeared to restore placental architecture. Epigenetically, folic acid supplementation suppressed histone deacetylases1 (HDAC1) expression, elevated H3K9ac levels and enhanced trophoblast proliferation.

conclusionsOur research suggests that dysregulation of the VPA-hypoxanthine axis may serve as a hallmark of FGR-associated metabolic stress. Folic acid may exerts potential dual therapeutic effects by correcting placental architecture through Lb normalization and initiating epigenetic reprogramming via HDAC1 inhibition and acetylation at lysine 9 of histone H3 (H3K9ac). These findings indicate that folate metabolism could play a regulatory role in placental gene transcription and fetal growth trajectories.

Indexed as

Epigenesis, GeneticFetal Growth RetardationFolic AcidPlacentaAdultAmniotic FluidDNA MethylationFemaleHistone Deacetylase 1HistonesHumansPregnancyValproic AcidFolic AcidHDAC1 protein, humanHistone Deacetylase 1HistonesValproic AcidEpigeneticFetal growth restrictionFolic acidMetabolismPlacenta

Identifiers

PMID41444682
PMCPMC12729199

What Socratic holds

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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 Socratic graph.