Researchers discovered how folic acid deficiency during pregnancy may lead to neural tube defects—serious birth conditions affecting the brain and spine. Using mouse models, scientists found that low folate causes DNA damage that disrupts how genes are organized and expressed in developing neural tissue. This damage prevents important genes from working properly during the critical early weeks when the neural tube (which becomes the brain and spinal cord) is forming. These findings help explain why folic acid supplements are so important for pregnant women and may lead to better prevention strategies.

The Quick Take

  • What they studied: How folic acid deficiency causes DNA damage that interferes with normal gene function during early fetal development, specifically in the formation of the neural tube (the structure that becomes the brain and spinal cord).
  • Who participated: This was a laboratory study using mouse models designed to mimic neural tube defects seen in humans. No human subjects were directly studied, but the findings are based on biological mechanisms relevant to human development.
  • Key finding: Mice with folate deficiency showed excessive DNA breaks that disrupted the 3D organization of genes, preventing important developmental genes from being properly activated during the critical window when the neural tube forms.
  • What it means for you: This research strengthens the scientific understanding of why folic acid supplementation before and during pregnancy is crucial for preventing neural tube defects. If you’re planning pregnancy or are pregnant, adequate folic acid intake (400-800 micrograms daily) appears even more important based on this mechanism.

The Research Details

This was a laboratory-based research study using genetically modified mouse models that naturally develop neural tube defects when exposed to folate deficiency. Researchers examined the DNA and gene organization in developing neural tissue from these mice, comparing normal development to development with folate deficiency.

The scientists used advanced molecular techniques to identify where DNA breaks occurred, how these breaks affected the 3D structure of genes, and which developmental genes were disrupted. They looked at the physical organization of DNA in the nucleus—how genes are packaged and positioned relative to each other—and how this organization changed with folate deficiency.

The study focused on understanding the biological mechanism rather than testing a treatment or intervention. This type of research is essential for understanding the ‘why’ behind known health risks, which can eventually lead to better prevention and treatment strategies.

Understanding the exact biological mechanism of how folate deficiency causes birth defects is important because it validates current prevention recommendations and may lead to improved strategies. By identifying that DNA damage and gene organization disruption are key factors, researchers can potentially develop new approaches to protect fetal development or identify which women are at highest risk.

This study was published in Advanced Science, a reputable peer-reviewed journal. The research used established laboratory techniques and mouse models that are standard in developmental biology research. However, because this is laboratory research in animals rather than human studies, the findings need to be confirmed in human populations. The study provides mechanistic evidence supporting what we already know about folic acid’s importance, rather than discovering entirely new information.

What the Results Show

The main discovery was that folate deficiency causes excessive DNA double-strand breaks (damage to both strands of the DNA molecule) in developing neural tissue. These breaks don’t just damage individual genes—they disrupt the entire 3D organization of the genome, which is like scrambling the filing system in a library.

When DNA breaks occurred in active genes (genes that are being used to make proteins), they caused RNA polymerase II (the molecular machine that reads genes) to stall and stop working. This prevented the genes from being properly expressed, meaning the instructions weren’t being read and carried out.

The researchers found that DNA breaks were especially concentrated near the start of genes and in regulatory regions called enhancers. These enhancers are like remote control switches that turn genes on and off. When breaks occurred in these critical control regions, they disrupted the loops of DNA that normally bring enhancers into contact with their target genes, preventing proper gene activation.

Most importantly, the genes that were disrupted by this DNA damage are known to be essential for normal neural tube closure—the process where the flat neural tissue folds into a tube to form the brain and spinal cord. When these genes don’t work properly, neural tube defects develop.

The study identified that the severity of DNA breaks correlated with distance from gene start sites, meaning breaks were more concentrated in the most critical regulatory regions. The researchers also found that the specific genes disrupted in their mouse model matched genes that are abnormally expressed in human neural tube defects, suggesting the mechanism they discovered in mice is relevant to human birth defects.

This research builds on decades of evidence showing that folic acid deficiency increases neural tube defect risk. Previous studies established the correlation and showed that folic acid supplementation prevents most cases. This new research explains the biological mechanism—the ‘how’ and ‘why’ behind that prevention. It confirms that the mechanism involves DNA damage and gene regulation disruption, which aligns with other research on folate’s role in DNA synthesis and repair.

This study was conducted in laboratory mice, not humans, so while the biological mechanisms are likely relevant to human development, they haven’t been directly proven in human pregnancies. The study examined the mechanism but didn’t test whether preventing the DNA breaks could prevent neural tube defects. Additionally, the study used mouse models specifically bred to develop neural tube defects, which may not perfectly represent all cases of human neural tube defects. The research provides important mechanistic insights but should be considered part of the broader evidence base rather than definitive proof of causation in humans.

The Bottom Line

Women planning pregnancy or who are pregnant should ensure adequate folic acid intake of 400-800 micrograms daily, as recommended by health organizations. This research provides additional biological evidence supporting these well-established recommendations. Women with a family history of neural tube defects may benefit from discussing higher folic acid doses (up to 4,000 micrograms daily) with their healthcare provider. Confidence level: High—this research strengthens existing recommendations rather than changing them.

This research is most relevant to: pregnant women and those planning pregnancy; women with a family history of neural tube defects; healthcare providers counseling women about pregnancy; public health officials developing prevention strategies. This research doesn’t change recommendations for the general population but provides deeper understanding of why current recommendations exist.

Folic acid’s protective effect against neural tube defects occurs during the first 28 days of pregnancy, often before a woman knows she’s pregnant. This is why folic acid supplementation should begin before conception. The benefits of adequate folate status develop over weeks to months of consistent intake before pregnancy.

Want to Apply This Research?

  • Track daily folic acid supplementation intake (target: 400-800 micrograms) and log dietary sources of folate (leafy greens, legumes, fortified grains) to ensure adequate total intake before and during pregnancy.
  • Set a daily reminder to take folic acid supplements at the same time each day. Add folate-rich foods to meal planning (spinach, broccoli, lentils, fortified cereals). If planning pregnancy, start supplementation at least one month before attempting conception.
  • Track consistency of supplementation over weeks and months. Monitor dietary folate intake through food logging. For women planning pregnancy, maintain tracking through the first trimester when neural tube formation is critical. Share supplementation records with healthcare provider at prenatal visits.

This research describes laboratory findings in animal models and should not replace medical advice from your healthcare provider. While this study provides mechanistic evidence supporting folic acid supplementation, it does not change current medical recommendations. Women planning pregnancy or who are pregnant should consult with their healthcare provider about appropriate folic acid supplementation levels, especially those with family history of neural tube defects or taking medications that affect folate metabolism. This information is for educational purposes and is not a substitute for professional medical diagnosis, treatment, or advice.