Epigenetic Effects of Manipulating Mouse Oocytes and Preimplantation Embryos.Rocio M. Rivera, Ph.D.

Abstract

Genomic imprinting is defined as parent-specific gene expression. Imprinted genes are a small subset of genes found in clusters throughout the mammalian genome. The correct allelic expression of these genes is directed by epigenetic modifications (established during gametogenesis) of the cluster's regulatory region (ICR). These genes are involved in the regulation of growth and development of both fetus and placenta as well as in neurobehavioral processes. Several syndromes exist that are the result of misregulation of imprinted genes. Recent retrospective studies have cautioned of an apparent increase in the incidence of loss-of-imprinting (LOI) syndromes in children conceived through assisted reproductive technologies (ART). In the mouse, we and others have shown that manipulations of gametes (i.e. superovulation) and preimplantation embryos (i.e. culture and/or transfer) can result in LOI. We showed that embryo transfer induced biallelic expression of several imprinted genes in extraembryonic tissues of d9.5 concepti. Furthermore, a superimposed embryo culture treatment caused a more severe misregulation of these genes in extraembryonic tissues. In addition, embryo culture also resulted in LOI in the fetus. Further, expression of the repressed allele of two imprinted genes was associated with loss of methylation at their ICRs. Although a relationship between ART and LOI has been established, the cellular and molecular mechanisms involved in this outcome are not known. Ongoing investigations are aimed at elucidating how each of theses procedures affect global DNA methylation and the expression of proteins involved in regulating the epigenome in oocytes and preimplantation embryos.