INSULIN-LIKE GROWTH FACTOR-I STIMULATES GROWTH OF MOUSE PREIMPLANTATION EMBRYOS INVITRO

Because recent studies have particularly implicated the insulin growth factor family in early development, the effects of insulin-like growth factor (IGF-1) on the development of mouse embryos in vitro were investigated in detail. When added to the medium for culture of two-cell embryos, IGF-1 stimulated the number of cells in the resultant blastocysts after 54 hr, entirely by increasing the number of cells in the inner cell mass (ICM) (16.0 +/- 0.5 vs. 12.6 +/- 0.5 cells/ICM). This stimulation was also achieved when ICMs were isolated from blastocysts prior to culture for 24 hr with IGF-1 (22.3 +/- 1.0 vs. 17.5 +/- 0.8 cells/ICM). There was no effect of IGF-1 on trophectoderm (TE) cell proliferation. In morphology studies, IGF-1 also increased the proportion of blastocysts (62% +/- 3% vs. 49% +/- 4%) while decreasing the number of embryos remaining as morulae (32% +/- 3% vs. 38% +/- 2%) or in the early cleavage stages (7% +/- 3% vs. 13% +/- 3%) after 54 hr culture from the two-cell stage. All these effects were achieved with EC50s of approximately 60 pM IGF-1, which is in the range for IGF-1 receptor mediation; however, cross reaction with insulin, IGF-2, or other unknown receptors is not excluded. Nonetheless, the results show that physiological concentrations of IGF-1 (17-170 pM, 0.1-1 ng/ml), which have been observed in the reproductive tract, affect the early embryo, suggesting a normal role for this factor in the regulation of growth of the developing conceptus before implantation.