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Updated: Nov 21, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Maternal folic acid impacts DNA methylation profile in male rat offspring implicated in neurodevelopment and
Xinyan Wang1, Zhenshu Li1, Yun Zhu2,3
1Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.
Insights
Maternal folic acid (FA) intake during pregnancy influences offspring brain development. FA impacts epigenetic regulation of genes involved in neurodevelopment and learning/memory in male rat offspring.
Area of Science:
- Neuroscience
- Epigenetics
- Developmental Biology
Background:
- Periconceptional folic acid (FA) supplementation is known to prevent neural tube defects and enhance offspring cognitive function.
- The specific genes and epigenetic pathways regulated by FA during neurodevelopment remain largely uncharacterized.
Purpose of the Study:
- To investigate the epigenetic mechanisms by which folic acid affects neurodevelopment.
- To identify differentially methylated genes and pathways in the brain of male rat offspring exposed to varying maternal folic acid levels.
Main Methods:
- Utilized methylated DNA immunoprecipitation (MeDIP) coupled with high-throughput sequencing (chip-seq) to assess genome-wide DNA methylation profiles in rat brain tissue.
- Employed DAVID and KEGG pathway analysis to identify differentially methylated genes (DMGs) and associated biological pathways.
Main Results:
- Maternal folate deficiency or supplementation led to significant alterations in DNA methylation patterns in male rat offspring brains.
- Identified 1939 DMGs in the folate-deficient group and 1498 DMGs in the folate-supplemented group compared to controls.
- Discovered overlapping and distinct methylation changes associated with neurodevelopment and learning/memory pathways under different maternal FA intake conditions.
Conclusions:
- Maternal folic acid intake during pregnancy epigenetically regulates genes and pathways crucial for neurodevelopment and cognitive functions in male offspring.
- Both folate deficiency and supplementation during gestation induce differential DNA methylation, highlighting the critical role of adequate FA levels for healthy brain development.
Background:
Periconceptional folic acid (FA) supplementation not only reduces the incidence of neural tube defects, but also improves cognitive performances in offspring. However, the genes or pathways that are epigenetically regulated by FA in neurodevelopment were rarely reported.
Methods:
To elucidate the underlying mechanism, the effect of FA on the methylation profiles in brain tissue of male rat offspring was assessed by methylated DNA immunoprecipitation chip. Differentially methylated genes (DMGs) and gene network analysis were identified using DAVID and KEGG pathway analysis.
Results:
Compared with the folate-normal diet group, 1939 DMGs were identified in the folate-deficient diet group, and 1498 DMGs were identified in the folate-supplemented diet group, among which 298 DMGs were overlapped. The pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in response to maternal FA intake during pregnancy, and there were some identical and distinctive potential mechanisms under FA deficiency or FA-supplemented conditions.
Conclusions:
In conclusion, genes and pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in male rat offspring in response to maternal FA deficiency or supplementation during pregnancy.
