Synergistic Effects of Folic Acid and n-3 Polyunsaturated Fatty Acid in Preventing Neural Tube Defects in Diabetic Mice

The present study aimed to investigate whether a combination of folic acid (FA) and n-3 polyunsaturated fatty acids (PUFA) has a better preventive effect on maternal diabetes-induced neural tube defects (NTD) than FA alone. The experiment included five groups of pregnant mice: healthy control (HC), diabetes mellitus control (DMC), diabetes + n-3 PUFA (DMn-3), diabetes + FA (DMFA), and diabetes + FA + n-3 PUFA (DMFA + n-3). The incidence of NTD in DMFA + n-3 (1.04%) was significantly lower than that in DMFA (8.57%) and DMn-3 (7.82%). The incidence of NTD in DMFA and DMn-3 was significantly lower than that in DMC (19.41%). DMFA + n-3 had a lower apoptosis of neuroepithelial cells, a lower expression of P53 and Bax, and a higher expression of Pax3 and Bcl-2, compared with DMFA and DMn-3. Combination of FA and n-3 PUFA attenuated diabetes-induced hypermethylation of Pax3, overexpression and overactivity of Dnmt3b, abnormal expression of genes involved in one-carbon metabolism and elevation of homocysteine, and these improving effects were better than FA or n-3 PUFA alone. In conclusion, the combination of FA and n-3 PUFA has a synergistic effect on preventing maternal diabetes-induced NTD.