One-carbon metabolism and epigenetic regulation of embryo development

Abstract

One-carbon (1C) metabolism consists of an integrated series of metabolic pathways that include the folate cycle and methionine remethylation and trans-sulfuration pathways. Most, but not all, 1C metabolic enzymes are expressed in somatic cells of the ovary, mammalian oocytes and in preimplantation embryos. The metabolic implications of this, with regard to the provision of methyl donors (e.g. betaine) and 1C cofactors (e.g. vitamin B12), together with consequences of polymorphic variances in genes encoding 1C enzymes, are not fully understood but are the subject of ongoing investigations at the authors’ laboratory. However, deficiencies in 1C-related substrates and/or cofactors during the periconception period are known to lead to epigenetic alterations in DNA and histone methylation in genes that regulate key developmental processes in the embryo. Such epigenetic modifications have been demonstrated to negatively impact on the subsequent health and metabolism of offspring. For this reason, parental nutrition around the time of conception has become a focal point of investigation in many laboratories with the aim of providing improved nutritional advice to couples. These issues are considered in detail in this article, which offers a contemporary overview of the effects of 1C metabolism on epigenetic programming in mammalian gametes and the early embryo.