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A paternal diet for offspring success?

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Science Translational Medicine  19 Apr 2017:
Vol. 9, Issue 386, eaan2780
DOI: 10.1126/scitranslmed.aan2780


Supplementation of the diet of male mice with methyl donors, such as methionine and folic acid, prior to mating impaired learning, memory, and metabolic functions in the offspring.

Methylation of DNA is an epigenetic regulatory mechanism of gene expression. Methylation can occur in gene promoters and regulatory regions and results in the repression of gene expression. Sources of methyl donors come from the diet and include the essential amino acid L-methionine, as well as methylation pathway–related intermediates and cofactors, such as choline, folic acid, betaine, and vitamin B12. The dietary intake of these methyl donors by women prior to and during pregnancy is known to be important for fetal and early childhood development. As a father’s germline can contribute heritable epigenetic changes to his offspring, it is important to question whether or not paternal dietary intake of methyl donors has any effect on offspring health.

In a recent study, Ryan et al. determined how the transmission of diet-induced epigenetic changes from father to offspring affected cognition, neural plasticity, and metabolism in the offspring. Male mice were fed standard control diets or methyl donor supplemented diets for the 6 weeks prior to mating. Once the subsequent offspring reached adulthood, various cognitive, behavioral, metabolic, and molecular analyses were performed. Mice born of fathers fed the methyl donor supplemented diets displayed no differences in motivational, perceptual, or motor capabilities but did show hippocampus-dependent spatial learning deficits and impaired contextual fear conditioning. On a physiological level, offspring from fathers fed the methyl donor supplemented diet showed reduced long-term potentiation and decreased hippocampal synaptic plasticity. In addition, they showed increased DNA methylation and decreased expression of the gene encoding the neuronal learning and memory regulator hippocampal BK channel beta-subunit 2 (Kcnmb2). Overexpression of Kcnmb2 in these offsprings rescued their epigenetically inherited cognitive impairments. Not only was neural biology and cognition altered, but systemic metabolism was shifted in offspring of fathers fed the methyl donor supplemented diet.

This study reveals the importance of methyl donors in the diet of male mice in the period just prior to mating. Over-supplementation of these nutrients in the fathers’ diet resulted in decreases in cognition and metabolism in their offspring. Future studies are needed to determine whether similar patterns exist in humans.

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