Intrinsic oxidative stress causes either 2-cell arrest or cell death depending on developmental stage of the embryos from SOD1-deficient mice

Oxidative stress characterized by elevated reactive oxygen species is a well-known cause of developmental arrest and cellular fragmentation in the development of in vitro-produced embryos. To investigate the effects of intrinsic oxidative stress on the early development of embryos, oocytes from superoxide dismutase 1 (SOD1)-deficient mice resulting from in vitro fertilization, followed by culture for 4 days, were examined. Development of all embryos from SOD1-deficient oocytes was arrested at the 2-cell stage under conventional culture conditions with atmospheric oxygen (20% O-2). Significantly higher levels of superoxide were detected in SOD1-deficinet embryos cultured under 20% O-2 using dihydroethidium. Among treatments with antioxidants, only hypoxic culture with 1% O-2 negated the 2-cell arrest and advanced the development of the embryos with efficacy similar to that in wild-type embryos. Mitochondrial function was investigated because its malfunction was a suspected cause of 2-cell arrest. However, respiratory activity, ATP content and mitochondrial membrane potential in the 2-cell embryos were not markedly affected by culture with 20% O-2. When embryos from SOD1-deficient oocytes were first developed to the 4-cell stage under 1% O-2 culture and were then transferred to 20% O-2, most of them developed to the morula stage but underwent total degeneration thereafter. Thus, oxidative stress was found to damage embryos differentially, depending on the developmental stage. These results suggest that embryos derived from SOD1-deficient mouse oocytes are an ideal model to investigate intrinsic oxidative stress-induced developmental abnormality.