Evidence map›Paper›PMID 41044654›Full record

ArticleClinical epigenetics2025

Maternal glucose concentrations and DNA methylation of genes related to the PPAR signaling pathway in human placenta: insights for maternal glucose concentrations' effects on neonatal anthropometrics.

Likang Li, Lei Zhang, Yafei Chen, Fen Yang, Xiuxia Song, Hong Liang, Wei Yuan, Honglei Ji, Min Luan, Maohua Miao

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Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Likang LiShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Public Health, Fudan University, Shanghai, 200237, China.
Lei ZhangMinhang District Maternal and Child Health Hospital, Shanghai, China.
Yafei ChenDepartment of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Fen YangInstitute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Xiuxia SongShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
Hong LiangShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
Wei YuanShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
Honglei JiShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China. hongleijish@163.com.
Min LuanShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. min.luan@sjtu.edu.cn.
Maohua MiaoShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.

Funding

Innovation Promotion Program of NHC and Shanghai Key Labs RC2024-05National Natural Science Foundation of China 22276125National Natural Science Foundation of China 22406132National Natural Science Foundation of China 82404275Shanghai Sixth People's Hospital Grant Award ynqn202425Three-year action plan for strengthening the construction of the public health system in Shanghai GWVI-11.2-YQ24
6 · The paper itself

Abstract

backgroundAccumulating evidence indicates that elevated maternal glucose concentrations during pregnancy are associated with adverse birth outcomes, but the mechanistic underpinnings remain unclear. This study aimed to evaluate the associations between maternal glucose concentrations and DNA methylation levels in genes related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the human placenta and explore the potential mediating role of placental DNA methylation in the relationship between maternal glucose concentrations and neonatal anthropometric measures.

methodsMaternal glucose concentrations were obtained from medical records, and neonatal anthropometric parameters were measured in 335 mother-infant pairs. DNA methylation levels of 14 genes related to the PPAR signaling pathway were analyzed in placental samples. Multiple linear regression models and mediation analyses were used to examine the associations and potential mediation effects.

resultsHigher maternal fasting plasma glucose (FPG) concentrations were generally associated with hypomethylation of genes related to the PPAR signaling pathway, with stronger effects in male neonates. Maternal 1-h plasma glucose concentrations after the glucose challenge test exhibited weaker but consistent patterns. Mediation analyses indicated that hypomethylation of ACAA1 mediated 29.00% (Indirect effect [IE]: β = 0.07; 95% confidence interval [CI] 0.02, 0.14) and 21.75% (IE: β = 0.07; 95% CI 0.00, 0.18) of the effects of FPG concentrations on increased neonatal abdominal and back skinfold thickness, respectively, while ACADM hypomethylation mediated 15.39% (IE: β = 0.03; 95% CI 0.00, 0.08) and 17.69% (IE: β = 0.06; 95% CI 0.00, 0.13) of these effects.

conclusionsElevated Maternal glucose concentrations were associated with hypomethylation of genes related to the PPAR signaling pathway. Specifically, hypomethylation of ACAA1 and ACADM may partially mediate the impact of maternal glucose concentrations on increased neonatal anthropometric measures. These findings provide mechanistic insights into potential epigenetic pathways linking maternal glucose concentrations to neonatal anthropometric outcomes.

Indexed as

Blood GlucoseDNA MethylationPeroxisome Proliferator-Activated ReceptorsPlacentaAdultAnthropometryFemaleHumansInfant, NewbornMalePregnancySignal TransductionBlood GlucosePeroxisome Proliferator-Activated ReceptorsDNA methylationPlacentaPlasma glucosePPAR signaling pathway

Identifiers

PMID41044654
PMCPMC12495655

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.