While it is recognized that maternal departures from the optimum of dietary methyl donor intake, such as folic acid, methionine or vitamine B12, can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake inﬂuences behavioral and cognitive functions in the next generation.
Epigenetic regulation of gene expression is mainly featured by the methylation of cytosine nucleotides. Abundant methylation in gene promotors usually leads to reduced expression and thus silencing of gene expression. This kind of regulation may play an important role in the regulation of neural functions and behavior.
As has been shown before, DNA methylation patterns are sensitive to diet. Food-derived nutrients such as choline and methionine are prominent sources of methyl donors. Dietary folate is critical to the synthesis of S-adenosylmethionine (SAM), another important methyl substrate. Insufﬁcient maternal folic acid (FA) intake has long been associated with elevated risk for neural tube defects. Interestingly, there is increasing evidence that excessive consumption of methyl donors may have deleterious effects and result in adverse health outcomes in directly exposed individuals. However it has not been addressed whether a diet rich in methyl donors in male individuals affects the offspring.
Therefore DP Ryan and colleagues fed male mice six weeks prior to mating with a methyl donor-enriched diet containing folic acid, L-methionine, choline, zinc, betaine and vitamine B12 and tested offspring of the F1 and F2 generations.
In tests for spatial learning and memory function, F1 mice whose fathers were fed with methyl donor-rich diet (MD-offspring) showed impairments that seemed to be independent of motivational, perceptual or motor differences. Additionally deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations became obvious.
The authors conclude that paternal dietary factors influence cognitive and neural functions in mouse offspring. Furthermore they suspect that also in humans an excessive intake of methyl donors might have adverse consequences.
DP Ryan, KS Henzel, BL Pearson, ME Siwek, A Papazoglou, L Guo, K Paesler, M Yu, R Müller, K Xie, S Schröder, L Becker, L Garrett, SM Hölter, F Neff, I Rácz, B Rathkolb, J Rozman, G Ehninger, M Klingenspor, T Klopstock, E Wolf, W Wurst, A Zimmer, H Fuchs, V Gailus-Durner, M Hrabě de Angelis, K Sidiropoulou, M Weiergräber, Y Zhou and D Ehninger. A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice. Mol Psychiatry. 2017 Apr 4. doi: 10.1038/mp.2017.53.