Phorbol ester-mediated modulation of cell proliferation and primary differentiation of mouse preimplantation embryos

The tumour promoter, phorbol myristate acetate (PMA) at concentrations of 5–50 ng/ml substantially affected 2-, 4-, 8-cell and morula mouse embryos cultured in vitro. PMA evoked a delay of cell growth and caused premature cell differentiation. In the former there was a formation of binuclear blastomeres, in the latter of giant cell formation in trophectoderm of blastocyst and premature cavitation. PMA-mediated delay of growth rate was completely reversible in 8-cell embryos, partially reversible in 4-cell embryos and poorly reversible, if at all, in 2-cell embryos. In the presence of PMA, nuclear DNA synthesis proceeded although the rate of nuclear labelling with [³H]thymidine was lower than in the control. Blastomeres of some 2-cell embryos treated with PMA fused, resulting in the formation of 1-cell embryos.