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 (α-TGF) ligand, PAF:acetylhydrolase 1b (Pafah1b; α₁, α₂, and β 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 α₁ 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, α₂ or β subunit of Pafah1b, nor did they effect α-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.