Uteroglobin Induces the Development and Cellular Proliferation of the Mouse Early Embryo

Two-cell mouse embryos cultured in vitro in the presence of either purified rabbit uteroglobin (UG) or recombinant human UG developed and proliferated faster than controls cultured in the absence of this protein. Both the percentage of embryos developing to the blastocyst stage and the number of cells per embryo were increased. Treatment with UG for 3 hr was enough to trigger this response. The effect of UG was blocked by genistein, an inhibitor of tyrosine protein kinases, suggesting the involvement of these kinases in the stimulation of the embryo by UG. To further support this suggestion, embryos were metabolically labeled in vitro with [32P] and the phosphorylated proteins were immunoprecipitated with anti-phosphotyrosine. Analysis of the immunoprecipitates by SDS-PAGE showed that UG induced the phosphorylation of several proteins of M(r) between 200 and 37 kDa. This induction was observed after 1 hr of stimulation with UG and further increased after 3 hr of treatment. Since UG is synthesized and secreted in the uterus and the oviduct, these results suggest a physiological role of this protein in the correct development of the embryo in vivo.