Variations Of DNA Methylation And Ultrastructure In Fetal Rats' Brain With Maternal Folate Deficiency

Purpose: To verify the effect of folate deficiency on fetal rats?intrauterine brain development, the change of DNA methylation and ultrastructure in fetal rats?brain with maternal folate deficiency was studied. Our research was expected to provide some evidence on the aspect of DNA and cellular ultrastructure. Method: Female Sprague-Dawley rats, 30 in the folate deficient group and 20 in the control group, received a purified diet without or with folate 2mg per Kg diet. After 14 d of feeding the rats were mated. The diets were continued throughout gestation. On day 20 of gestation the dams were killed , serum folate concentration was assayed and fetal development was observed. DNA methylation level in fetal brain was assayed by high performance liquid chromatography and the ultrastructrue of lobus frontalis was observed by transmission electronmicroscopy. Correlation analysis was processed among serum folate concentration of dam and fetus and DNA methylation level in fetal brain. Results: 1.Dams in deficient group had significant lower serum folate concentration before mating or at the end of gestation than those in control group. Hypersegmented neutrophils were present in deficient group. Fetal serum folate concentration in this group was lower than those in control group too and was associated with macrocyte and. 2. The DNA methylation level in fetal brain in deficient group was also lower than that in control group. serum folate concentration of dams and fetus and DNA methylation level in fetal brain were positively correlated. 3. The ultrastructrue of lobus frontalis was changed such as: (1) the large nuclear indetations; the distension of part of perinuclear space; the reduction of heterochromatine and ribosome content of the cytoplasm; the swollen cytoplasmic organelles in neuron.(2) similar changes were found in some gliocyte.(3) neuropil was swollen and partially damaged. Conclusion: 1.Giving female SD rats folate-free diet from 2 weeks before mating to the end of gestation could produce an effective pregnant model which had folate deficiency at second and third trimesters of gestation. The fetal rats suffered macrocyte and intrauterine 2 ~{~tII~R DNA fl~*. growth restriction, but didn抰 have neural tube defect. 2.The DNA methylation level in fetal rat抯 brain decreased when it抯 dam suffered folate deficiency. This kind of change was positively correlated with serum folate concentration of dams and fetus. It is possibly one of the mechanism of folate deficiency imparing the fetal rat抯 brain development. 3.Maternal folate deficiency could change the ultrastructure of fetal rat抯 lobus frontalis. It maybe lead to abnormality of neuronal function and would disturb fetal brain development. 4. Folate supplement during periconception should be prolonged to delivery.