A considerable proportion of the offspring born from somatic nuclear transfer (sNT)-derived and in vitro-produced (IVP) embryos, particularly in ruminants and mice, is affected by multiple abnormalities of which a high birth weight is the predominant feature; a phenomenon that has been called "large offspring syndrome (LOS)". The underlying mechanisms are largely unknown at present, but changes in epigenetic modifications occurring during preimplantation development resulting in perturbed embryonic and fetal gene expression patterns are thought to be involved in the syndrome. This review summarizes results from studies comparing mRNA expression patterns from IVP and sNT-derived embryos to those of their in vivo counterparts, which are regarded as the "gold standard". Numerous aberrations have been observed 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 studies during preimplantation embryo development to gain insight in the molecular, preferentially epigenetic, mechanisms regulating embryonic and fetal development. Understanding these mechanisms will help to improve biotechnologies applied to early embryos in all species including humans.