The effects of sodium selenite and selenomethionine on murine limb development in culture

Abstract

The present study was performed to determine whether the lack of selenium-induced limb defects in mammals is due to either differences in pharmacokinetics or tissue sensitivity to the compound, or both. Sodium selenite (SS) and selenomethionine (SM) were added to BGJb medium containing 20% fetal bovine serum, in which limbs from CD-1 mouse embryos taken 12 d following conception were cultured. Concentrations of SS and SM ranged from 2 to 20 times the level of selenium normally present in fetal bovine serum. Limbs were grown for 72 h, fixed, stained with Alcian blue GX to highlight cartilage anlagen, and analyzed to determine tissue and anlage areas and shape factors. Sodium selenite induced a concentration-response maldevelopment of ulnar, radius, and humerus anlagen and delayed development of phalanges, whereas SM did not. Changes in development became obvious at SS levels four times normal. The size and length of anlagen also decreased. At six times the concentration of SS, areas occupied by cartilage anlagen were decreased 20-fold, with virtually no chondrogenesis evident in phalanges at higher concentrations. The results of these studies indicate that SS can cause deficits in early mammalian limb development if the element is allowed to reach the developing tissue,more » whereas the SM does not. The authors conclude that tissue differences in response and placental transfer may account for the differences seen among species.« less