Comparative effects of essential and nonessential metals on preimplantation mouse embryo development in vitro

It is well recognized that deficiencies of essential trace elements during early development can result in structural abnormalities and/or embryonic death. Recently, there has been increasing interest in the concept that small excesses of essential metals can also have negative effects on the developing embryo. We hypothesized that, with respect to toxicity, metals with similar physico-chemical properties would act by similar mechanisms to influence the preimplantation embryo. In the current study we investigated the influence of four essential (Cu, Mn, Fe, Zn), and eight nonessential (Cr, Hg, Pb, V, Al, Ag, Cd, As) metals on mouse preimplantation embryonic development. Two cell stage mouse embryos were cultured for 72 h in media containing varying metal concentrations (0.05 - 200 microM). Embryo cell differentiation and proliferation were respectively assessed by scoring for blastocyst formation and final embryo cell number. Both nonessential and essential metals were embryotoxic at relatively low concentrations. However, in contrast to our expectations, at similar molar concentrations, redox active essential metals were less toxic than non-redox active nonessential metals. These data suggest that direct metal binding to critical membrane sites and/or intracellular ligands, including protein and nucleic acids, may trigger abnormal development and death prior to metal-associated oxidative damage.