Maternal Methyl Supplements in Mice Affect Epigenetic Variation and DNA Methylation of Offspring

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Abstract
This study was designed to determine if maternal dietary methyl supplements increase DNA methylation and methylation-dependent epigenetic phenotypes in mammalian offspring. Female mice of two strains were fed two levels of dietary methyl supplement or control diet prior to and during pregnancy. Offspring of these mice vary in phenotype, which is epigenetically determined and affects health and 2-y survival. Phenotype and DNA methylation of a long terminal repeat (LTR) controlling expression of the agouti gene were assayed in the resulting offspring. Methyl supplements increase the level of DNA methylation in the agouti LTR and change the phenotype of offspring in the healthy, longer-lived direction. This shows that methyl supplements have strong effects on DNA methylation and phenotype and are likely to affect long-term health. Optimum dietary supplements for the health and longevity of offspring should be intensively investigated. This should lead to public policy guidance that teaches optimal, rather than minimal, dose levels of maternal supplements.