Culture of preimplantation embryos and its long-term effects on gene expression and phenotype.

A growing number of medical, scientific and biotechnological procedures rely on culture of mammalian preimplantation embryos. This review presents currently available data on aberrant offspring development that sometimes arises from commonly applied in-vitro procedures in humans, ruminant species and mice. Comparison between mammalian species reveals similarities in the phenotypic abnormalities that are observed at fetal and perinatal stages of development. In particular, aberrant effects on fetal growth have been observed in multiple studies in which serum complemented the preimplantation culture medium. Although it remains to be determined whether there is a common causal mechanism(s) involved, several hypotheses have been put forward to account for the variety of the observed developmental abnormalities. One of these postulates that culture can result in the epigenetic deregulation of developmentally important genes, and that such epigenetic alterations would affect in particular the expression of genes that are subject to genomic imprinting. Imprinted genes play key roles in the control of fetal growth, and altered imprinting can cause growth defects. Some recent in-vitro culture studies on mice and ruminant species now lend support to this hypothesis.