Maternal methyl supplemented diets and epimutations in offspring

Abstract

Methyl supplemented diets are being promoted to combat various diseases. Consumption of one methyl supplement, folic acid, by expecting women has greatly reduced the incidence of neural tube defects in offspring. However, maternal consumption of folic acid and other related supplements can serve as methyl donors and lead to promiscuous epimutations in resulting offspring. CpG islands within promoter and intergenic regions and histone proteins might be indiscriminately targeted. Whether maternal consumption of such nutritional supplements is beneficial to progeny is likely due to the net balance of CpG sites and histone proteins subject to methylation. There could also be interindividual variability based on overall nutritional condition and genetic status. In this Chapter, we will explore epimutations that have been identified in offspring derived from rodent dams and pregnant women ingesting various methylsupplemented diets. The evidence of potential beneficial and conversely harmful effects of such maternal diets will also be considered, along with reported effects in offspring systems, in particular the central nervous system (CNS), that are especially susceptible to an in utero surfeit of methyl donors. Collective studies remain unresolved as to whether physicians should recommend to women seeking to become pregnant and those already pregnant whether it is in the best interest of their developing child to consume greater amounts of methyl donors beyond the current recommendations. This chapter might pave the way for additional studies needed to address the critical gaps in our understanding and allow women to make better-informed decisions about such supplements.