Previous studies showed that insulin promotes cell proliferation and morphological development of preimplantation mouse embryos. In this report, the receptor responsible for these actions and the cell populations that are affected were investigated. Insulin's 9% stimulation of blastocyst cell number was entirely due to a 23% increase in ICM cell number with an EC50 of 0.54 pM. This and the similar degrees of stimulation of immunosurgically isolated ICMs by both physiological and supraphysiological insulin concentrations suggest that insulin receptors are present on the ICM and respond to exogenous insulin transcytosed through the TE to promote expansion of the ICM cell numbers. In morphological studies, insulin increased the number of blastocysts and decreased the number of morulae by 10% after 54 h culture from 2-cell embryos with EC50s of about 0.95 pM. The equivalence of these EC50s suggests mediation of insulin's stimulation of blastocyst formation via insulin receptors which are functionally expressed around the time of compaction at the 8-cell stage. These results support our hypothesis that insulin has an important role in the regulation of growth during preimplantation development
