Maternal micronutrients and brain global methylation patterns in the offspring

Abstract

Objectives

Studies have established the association of maternal nutrition and increased risk for non-communicable diseases. It has been suggested that this involves epigenetic modifications in the genome. However, the role of maternal micronutrients in the one-carbon cycle in influencing brain development of the offspring through methylation is unexplored. It is also unclear whether epigenomic marks established during early development can be reversed by a postnatal diet. The present study reports the effect of maternal micronutrients and omega-3 fatty acids on global DNA methylation patterns in the brain of the Wistar rat offspring at three timepoints (at birth, postnatal day 21, and 3 months of age).

Method

Pregnant rats were divided into control (n = 8) and five treatment groups (n = 16 dams in each group) at two levels of folic acid (normal and excess folate) in the presence and absence of vitamin B₁₂ (NFBD, EFB, and EFBD). Omega-3 fatty acid supplementation was given to vitamin B₁₂ deficient groups (NFBDO and EFBDO). Following delivery, eight dams from each group were shifted to control diet and remaining continued on the same treatment diet.

Results

Our results demonstrate that maternal micronutrient imbalance results in global hypomethylation in the offspring brain at birth. At adult age the cortex of the offspring displayed hypermethylation as compared with control, in spite of a postnatal control diet. In contrast, prenatal omega-3 fatty acid supplementation was able to normalize methylation at 3 months of age.

Discussion

Our findings provide clues for the role of omega-3 fatty acids in reversing methylation patterns thereby highlighting its contribution in neuroprotection and cognition.

Keywords:

• Cortex
• Docosahexaenoic acid
• Folic acid
• Global methylation
• Hippocampus
• Omega-3 fatty acids
• Vitamin B₁₂

Acknowledgements

We thank the Department of Biotechnology, New Delhi, India for partially funding this project. We thank Mr Vinayak Dhawale for his assistance at the animal house.