Evaluation of the relationship between folic acid supplementation in pregnant mice and development of allergic airway disease in offspring

Objective: The fact that reduction in neural tube defects by use of folic acid supplement during pregnancy has been noticed in many studies; the use of folic acid supplementation increased world wide. Folic acid functions as a methyl donor in many biochemical reactions of the body. Recent studies indicate that the diet rich of methyl donor increase the risk of allergic airway disease because of epigenetic regulation assisted by methylation of DNA. There is limited evidence with regard to maternal folic acid supplementation effects on the development of allergic airway disease in life. This study aimed to evaluate the relationship between folic acid supplementation during pregnancy and allergic airway disease in offspring. Methods: Female BALB/c mice were randomized into four groups according to the folic acid supplementation in pregnancy; group 1 (whole pregnancy folic acid supplementation group), group 2 (first week of gestation folic acid supplementation group), group 3 (without folic acid supplementation group), group 4 (control group). Their offspring were sensitized and challenged with ovalbumin except the control group. Offspring were sacrificed after 24 hours of last nebulised ovalbumin administration for histological and immunohistochemical evaluation of lung tissues. Results: Epithelial and subepithelial smooth muscle thickness, VEGF and MMP-9 positive immunoreactivity are increased significantly in the folic acid supplemented groups in spite of without folic acid supplemented group. Moreover, folic acid supplementation during whole pregnancy group (group 1) was associated with thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (group 2). Conclusion: This study suggests that maternal folic acid supplementation during pregnancy increases allergic responses induced by ovalbumin challenge in offspring. Also the effect size increases as the duration and the cumulative dose increase. Keywords: Folic acid, Maternal supplementation, Allergic airway disease, Epigenetics