DEVELOPMENTAL BLOCKAGE OF MOUSE EMBRYOS CAUSED BY FATTY-ACIDS

Purpose: It has been shown that lipid peroxides derived from polyunsat urated fatty acids (PUFAs) inhibit the proliferation of various cells. In the meantime, it has been suggested that oxidative stress is close ly related to the developmental blockage of mammalian embryos cultured in vitro. In this study, we investigated the effects of various fatty acids on mouse embryo development in vitro, and the reversal of these effects by various antioxidants such as superoxide dismutase, ascorbi c acid, alpha-tocopherol, uric acid, and ethylenediaminetetraacetic ac id. Methods: Pronuclear and two-cell stage mouse (ICR) embryos were cu ltured in Biggers-Whitten-Whittingham medium with 0.3% bovine serum al bumin alone or complexed with one of the following fatty acids: palmit ic, stearic, oleic, linoleic, linolenic, or arachidonic acid, We also measured the fluorescence emission of embryos in media containing vari ous fatty acids in order to investigate the involvement of H2O2 or lip id peroxidation in embryo development. Results: Palmitic acid and PUFA s including linoleic acid inhibited the embryo development. The inhibi tory effect of PUFAs was attenuated by adding antioxidants into the me dia, while the inhibitory effect of palmitic acid was not, Both pronuc lear and two-cell stage embryos with PUFAs showed markedly more intens ive emissions than those under other conditions. Conclusions: These re sults suggest that lipid radicals can easily be generated in early sta ge embryos and that blastomeres are among the cells vulnerable to the damage by lipid peroxidation.