Mitotically Stable Modification of DNA Methylation in IGF2/H19 Imprinting Control Region Is Associated with Activated Hepatic IGF2 Expression in Offspring Rats from Betaine-Supplemented Dams

The growth-promoting action of betaine involves activation of GH/IGF-1 signaling, yet it remains unclear whether insulin-like growth factor 2 (IGF2), an imprinting gene, is affected by maternal dietary betaine supplementation. In this study, F1 offspring rats derived from dams fed basal or betaine-supplemented diet were examined at D21 and D63. Maternal betaine significantly upregulated the hepatic expression of IGF2 mRNA and protein in offspring rats at both D21 and D63, which was accompanied by enhanced hepatic IGF2 immunoreactivity and elevated serum IGF-2 level. Higher protein expression of betaine-homocysteine methyltransferase and DNA methyltransferase 1 was detected in the betaine group at D21, but not D63. However, hypermethylation of the imprinting control region of the IGF2/H19 locus at D21 was maintained at D63. These results indicate that maternal betaine modifies DNA methylation of IGF2/H19 imprinting control region in a mitotically stable fasion, which was associated with the activation hepatic IGF2 expression in offspring rats.