Microsomal mediated embryo toxicity due to superoxide radicals

Abstract

The transfer of toxic substances to the developing fetus with deleterious results on pregnancy outcome is well known. It is now clear that the preimplantation period of development is susceptible to such exposure. This early developmental period is a time of critical genetic determination and a period during which much membrane synthesis is occurring. Since disruption of membrane formation might be important in the disorganization of embryos, microsomal protein-mediated toxicity in mouse blastocysts was explored. The embryos were shown to be completely disorganized by exposure to induced microsomal proteins in the presence of NADPH. All of the embryos exposed died within 18 hr. The effect was completely eliminated by boiling the microsomes or by removal of NADPH. Decreasing toxicity of the exposure could be achieved by adding butyl hydroxy toluene, an antioxidant. An amount of 0.001 mg/ml resulted in 100% viability in the presence of microsomes and cofactors after 2 hr (33% viability after 18 hr); however BHT resulted in its own toxicity at 0.025 mg/ml. Superoxide dismutase, an enzyme that removes superoxide radicals by dismutation, was completely protective with as little as 0.6 IU of enzyme added to the incubation mixture.