Effect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early Weanling Intrauterine Growth Retarded Rats.

BACKGROUND/AIMS: The objective of this study was to examine the responses of p53 promoter methylation involved in kidney structure and function of early weaning intrauterine growth retarded (IUGR) rats to dietary folic acid supplementation.

METHOD: Sprague-Dawley rats were fed isocaloric diets containing either 21% protein diet (normal feed) or 10% protein diet throughout pregnancy and normal feed during lactation. After weaning, Offspring were then fed onto normal feed and normal feed supplemented with 5 mg folic acid / kg feed for a month, this produced 4 dietary groups (maternal diet/ weanling diet): Con, Folic, IUGR and IUGR+Folic. Renal function, renal structure, p53 promoter methylation and protein expression of offspring rats were measured at postnatal 2 months and 3 months.

RESULTS

Glomerular volume, blood urea nitrogen, 24 hours urine protein were significantly elevated in IUGR rats compared with Con rats but were decreased by dietary folic acid supplementation. p53 protein expression in IUGR rats were significantly higher than that in Con rats, and p53 promoter methylation status in IUGR rats was reduced significantly compared with Con rats. However, the changes in p53 gene expression and DNA methylation status of IUGR rats were reversed by dietary folic acid supplementation.

CONCLUSIONS

Our study showed for the first time that folic acid supplementation during early period of life could reverse the abnormality in renal p53 methylation status and protein expression, glomerular volume and renal function of IUGR rats offspring.