Insulin receptor substrate-1 is expressed at high levels in all cells of the peri-implantation mouse embryo.

Insulin and insulinlike growth factors are important for embryonic growth and metabolism. Intracellular transduction for these factors has not been studied in the preimplantation mouse embryo. Peri-implantation mouse embryos synthesize insulinlike growth factor (IGF)-II ligand, insulin receptor, IGF-I receptor, and IGF-II receptor and respond to IGF-II, IGF-I, and insulin metabolically and mitogenically. Maternal tissues in the oviduct and uterus are also sources of IGF-I and insulin. Signaling of IGFs occurs through insulin receptor substrate (IRS)-1 and IRS-2. This paper shows that IRS-1 mRNA and protein are highly expressed in preimplantation mouse embryos, in embryonic cell lines, and in cultured blastocyst outgrowths. IRS-1 mRNA and protein are detected in embryo-derived cell lines cultured to produce the three cell lineages (stem cells, endoderm, and trophoblast cells). IRS-1 mRNA is detected by reverse transcription-polymerase chain reaction (RT-PCR) in the E3.5 blastocyst before implantation and in F9 teratocarcinoma stem cells and parietal endoderm cells. IRS-1 mRNA is detected by Northern blot hybridization at high levels in stem cells and in differentiated progeny of F9 cells and C3H/NE trophectoderm cells. IRS-1 protein was detected in these cell lines and in an overexpressing CHO-IRS-1 fibroblast cell line by immunocytochemistry. Cultured blastocyst outgrowths are a model for implantation events of the trophoblast/placenta lineage and endoderm/yolk sac lineage. In the blastocyst outgrowth, IRS-1 protein is detected in inner cell mass cells (ICM cells), primitive endoderm, parietal endoderm, and trophectoderm cells. These data suggest that IRS-1 is expressed in all cell lineages of the peri-implantation mouse embryo and mediates some effects of insulin and IGFs at this stage.