An evaluation of propofol toxicity on mouse oocytes and preimplantation embryos

Mouse biological assays were used to investigate potential adverse effects of propofol on the oocyte's competence to fuse with spermatozoa and on the embryo's ability to develop to the blastocyst stage. Cumulus-enclosed metaphase II oocytes were exposed for 1 h to 0.01, 0.1, 0.4, 1 and 10 microg/ml propofol (Diprivan) and subjected to a sperm-oocyte fusion test based on the dye (Hoechst 33342) transfer technique. Oocytes exposed to 0.4, 1 and 10 microg/ml propofol showed a significant reduction in the rate of sperm fusion and underwent pronuclei formation at a rate similar to that of sperm fusion. In a second trial, mouse 1-cell and 2-cell embryos were exposed to varying propofol concentrations for 14h and then checked for subsequent development. Although adverse effects were not observed in 2-cell embryos, treatment of 1-cell embryos with propofol concentrations ranging from 0.01 to 10 microg/ml resulted in the inhibition of cleavage to blastocyst stage. We conclude that propofol can negatively influence fertilization in the mouse by impairing the oocyte's ability to fuse with spermatozoa, without interfering with the sperm-induced activation of the cell cycle. Moreover, we document the peculiar sensitivity to propofol of mouse 1-cell embryos as compared with 2-cell embryos.