Roles of one-carbon metabolism in preimplantation period--effects on short-term development and long-term programming--.
ABSTRACT One-carbon metabolism (OCM) can be seen as integrated metabolic pathways centered on the metabolism of two nutritional substances, folate and methionine. Mammalian oocytes and preimplantation embryos express almost all enzymes that participate in OCM, suggesting that they can independently metabolize OCM nutrients. A deficiency or excess of OCM nutrients and their metabolites during in vitro culture affects preimplantation development of mammalian embryos. Recent in vivo studies have demonstrated that specific OCM dietary interventions during the periconceptional (mainly oocyte growth and preimplantation) period can cause epigenetic alterations in DNA of offspring and program the long-term consequences in their health in adulthood. The epigenetic processes are likely to be implicated in the effects of OCM nutrients; however, understanding their effects at the level of specific genes and their implications in assisted reproductive technology will require further investigations.
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ABSTRACT: Folate plays a key role in the interactions between nutrition, fetal programming, and epigenomics. Maternal folate status influences DNA methylation, inheritance of the agouti phenotype, expression of imprinting genes, and the effects of mycotoxin FB1 on heterochromatin assembly in rodent offspring. Deficiency in folate and other methyl donors increases birth defects and produces visceral manifestations of fetal programming, including liver and heart steatosis, through imbalanced methylation and acetylation of PGC1-α and decreased SIRT1 expression, and produces persistent cognitive and learning disabilities through impaired plasticity and hippocampal atrophy. Maternal folate supplementation also produces long-term epigenomic effects in offspring, some beneficial and others negative. Deciphering these mechanisms will help understanding the discordances between experimental models and population studies of folate deficiency and supplementation.Trends in Endocrinology and Metabolism 03/2013; · 8.90 Impact Factor