In Vitro Fertilization Causes Epigenetic Modifications to the Onset of Gene Expression from the Zygotic Genome in Mice1

The effect of in vitro fertilization (IVF) and culture of mouse preimplantation embryos in vitro on the onset of expression of insulin-like growth factor 1 (IGF-1) ligand and receptor, insulin ligand and receptor, alpha-transforming growth factor (alpha-TGF) ligand, PAF:acetylhydrolase 1b (Pafah1b; alpha(1), alpha(2), and beta subunits of the enzyme), and the transcription requiring complex proteins (TRC) was examined. The IGF-1 ligand was detected in preimplantation embryos by immunofluorescence at all developmental stages tested. However, IVF and culture significantly reduced the amount of protein detected in the 8-cell embryo and blastocyst (P: < 0.001), and this was due to a delayed onset of expression of the mRNA for IGF-1 ligand from the zygotic genome. The expression of the alpha(1) subunit of Pafah1b was 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) zygotes were cultured in vitro. In vitro fertilization or ISF did not delay the onset of expression of TRC nor mRNA for the IGF-1 receptor, insulin receptor, 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 growth and survival.