Effects of glutathione depletion on selenite- and selenate-induced embryotoxicity in cultured rat embryos

Effects of depletion of reduced glutathione (GSH) on selenium (Se) embryoto xicity in cultured rat embryos were examined. Rat embryos at day 9.5 of ges tation were cultured for 48 h in the presence of Se as either sodium seleni te at 10 and 20 mu M or sodium selenate at 30 and 100 mu M. Embryonic GSH w as depleted by the addition of 0.1 mM of L-buthionine-[S,R]-sulfoximine (BS O) without embryotoxicity, i.e., significant growth retardation and malform ation of the embryos. Selenite at 10 mu M or selenate at 100 mu M significa ntly increased the incidence of malformation of the embryos. The incidence of selenite-induced malformation of the embryos at 20 mu M was significantl y decreased with BSO. On the contrary, the incidence of selenate-induced ma lformation at 30 mu M was significantly increased with BSO. It was noted th at the major malformed regions of the embryos by the embryotoxic concentrat ion of BSO alone were the same to those affected by selenite or selenate. I t was considered from these results that embryonic GSH was involved in the embryotoxicity of selenite and selenate. The embryotoxicity of selenate may not be mediated through the reduction to selenite. It was suggested that t he formation of selenodiglutathione and the oxidative stress were involved in the embryotoxicity of selenite and selenate, respectively. (C) 1999 Wile y-Liss, Inc.