In vitro fertilization causes epigenetic modifications to the onset of gene expression from the zygotic genome in mice

The effect of in vitro fertilization (IVF) and culture of mouse preimplanta tion embryos in vitro on the onset of expression of insulin-like growth fac tor 1 (IGF-1) ligand and receptor, insulin ligand and receptor, alpha-trans forming growth factor (alpha -TGF) ligand, PAF:acetylhydrolase 1b (Pafah1b; alpha (1), alpha (2), and beta subunits of the enzyme), and the transcript ion requiring complex proteins (TRC) was examined. The IGF-1 ligand was det ected in preimplantation embryos by immunofluorescence at all developmental stages tested. However, IVF and culture significantly reduced the amount o f protein detected in the 8-cell embryo and blastocyst (P < 0.001), and thi s was due to a delayed onset of expression of the mRNA for IGF-1 ligand fro m the zygotic genome. The expression of the <alpha>(1) subunit of Pafah1b w as first detected at the 2-cell stage in fresh embryos, but expression was significantly retarded (P < 0.001) when IVF and ISF (in situ-fertilized) zy gotes were cultured in vitro. In vitro fertilization or ISF did not delay t he onset of expression of TRC nor mRNA for the IGF-1 receptor, insulin rece ptor, <alpha>(2) or beta subunit of Pafah1b, nor did they effect alpha -TGF protein synthesis. Thus, IVF causes epigenetic modification in the normal pattern of expression of some but not all genes involved in normal embryo g rowth and survival.