Epigenetic reprogramming in early embryonic development: effects of in-vitro production and somatic nuclear transfer

A considerable proportion of offspring, in particular in ruminants and mice, born from nuclear transfer (NT)-derived and in-vitro-produced (IVP) embryos is affected by multiple abnormalities of which a high birthweight and an extended gestation length are the predominant features; a phenomenon that has been called 'large offspring syndrome' (LOS). The underlying mechanisms are largely unknown at present, but alterations of epigenetic modifications of embryonic and fetal gene expression patterns, primarily caused by alterations in DNA methylation are thought to be involved in this syndrome. In mammals, DNA methylation is essential for the regulation of transcription during development and differentiation. This review summarizes results from studies in which mRNA expression patterns from IVP and NT-derived embryos were compared with those of their in-vivo counterparts. Numerous aberrations have been found ranging from suppression of expression to de-novo overexpression or more frequently to a significant up- or down-regulation of a specific gene. These observations emphasize the need for further epigenetic studies during preimplantation embryo development to gain insight into the molecular regulation correlated with an undisturbed embryonic and fetal development. Understanding molecular mechanisms will aid improvements in biotechnologies applied to early embryos in all species, including humans.