Paternal methyl donor deficient diets during development affect male offspring behavior and memory-related gene expression in mice

It has become increasingly evident that the methylation of DNA, known as an epigenetic marker, affects behavior in animals. In our previous study, a methyl-donors (folate, methionine, and choline)-deficient (FMCD) diet during the juvenile period could be shown to affect anxiety-like behavior and fear memory, accompanied by alteration in some gene expression and their methylations in the hippocampus. One question is whether the fear memory of a parent affects the fear responses of offspring. To explore this question in the present study, C57BL/6 J male (F0) mice were given a FMCD diet from 3 to 12 weeks of age. After confirming the effect of the FMCD diet on the behavior and gene expression of F0 mice, their male offspring (F1-FMCD mice) were examined using the same behavioral batteries and genetic analysis. F0 diet-based differences in F1 behavior were observed, accompanied by the differences in the expression of memory-related genes (Camk2 alpha and PP1) and promoter methylation of the PP1 gene in the hippocampus. Our results add evidence that behavior and gene expression of the F1 generation could be altered due to differences in the father's intake of methyl-donor nutrients.