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Updated: Dec 25, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
The effect of folic acid deficiency on Mest/Peg1 in neural tube defects
Shaoyan Chang1, Jia Jing2, Shaofang Shangguan1
1Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
Objective:
Neural tube defects (NTDs) are one of the most common and serious birth defects in human beings caused by genetic and environmental factors. Folate insufficiency is involved in the occurrence of NTDs and folic acid supplementation can prevent NTDs occurrence, however, the underlying mechanism remains poorly understood.
Methods:
We established cell and animal models of folic acid deficiency to detect the methylation modification and expression levels of genes by MassARRAY and real-time PCR, respectively. Results and conclusion: In the present study, we found firstly that in human folic acid-insufficient NTDs, the methylation level of imprinted gene Mest/Peg1 was decreased. By using a folic acid-deficient cell model, we demonstrated that Mest/Peg1 methylation was descended. Meanwhile, the mRNA level of Mest/Peg1 was up-regulated via hypomethylation modification under low folic acid conditions. Consistent with the results in cell models, Mest/Peg1 expression was elevated through hypomethylation regulation in folate-deficient animal models. Furthermore, the up-regulation of Mest/Peg1 inhibited the expression of Lrp6 gene, a crucial component of Wnt pathway. Similar results with Lrp6 down-regulation of fetal brain were verified in animal models under folic acid-deficient condition. Taken together, our findings indicated folic acid increased the expression of Mest/Peg1 via hypomethylation modification, and then inhibited Lrp6 expression, which may ultimately impact on the development of nervous system through the inactivation of Wnt pathway.
Insights
Folic acid supplementation prevents neural tube defects (NTDs) by regulating gene methylation. Low folic acid reduces Mest/Peg1 methylation, increasing its expression and inhibiting Lrp6, impacting nervous system development.
Area of Science:
- Developmental Biology
- Epigenetics
- Nutritional Neuroscience
Background:
- Neural tube defects (NTDs) are common congenital abnormalities influenced by genetic and environmental factors.
- Folic acid supplementation is known to prevent NTDs, but the precise molecular mechanisms are not fully understood.
- Imprinted genes and epigenetic modifications, such as DNA methylation, are critical in embryonic development.
Purpose of the Study:
- To investigate the role of folic acid in regulating the methylation and expression of the imprinted gene Mest/Peg1 in the context of NTDs.
- To elucidate the downstream effects of altered Mest/Peg1 expression on key developmental pathways, specifically the Wnt signaling pathway.
- To establish the mechanistic link between folic acid deficiency, epigenetic changes, gene expression, and potential impacts on nervous system development.
Main Methods:
- Establishment of cellular and animal models simulating folic acid deficiency.
- Quantification of DNA methylation levels using MassARRAY.
- Measurement of gene and mRNA expression using real-time PCR.
- Analysis of gene expression changes in response to altered folic acid availability and epigenetic modifications.
Main Results:
- Folic acid-insufficient NTDs and folic acid-deficient models showed decreased Mest/Peg1 methylation.
- Low folic acid conditions led to hypomethylation and subsequent up-regulation of Mest/Peg1 mRNA and protein expression.
- Increased Mest/Peg1 expression was found to inhibit the expression of Lrp6, a key component of the Wnt pathway.
- Down-regulation of Lrp6 in fetal brain tissues was observed in folate-deficient animal models.
Conclusions:
- Folic acid promotes Mest/Peg1 expression through hypomethylation.
- The up-regulation of Mest/Peg1 under folate deficiency inhibits Lrp6 expression, potentially impacting nervous system development via Wnt pathway inactivation.
- These findings provide novel insights into the molecular mechanisms by which folic acid prevents NTDs.
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