P-158 - SOD1 haploinsufficiency exerts deleterious effects on the testis via activation of the autoimmune response in NZW mice

Abstract

The New Zealand black (NZB) × New Zealand white (NZW) F1 hybrid mouse spontaneously develops an SLE-like autoimmune condition. ROS originated from the NZB background have a functional role in triggering the fatal responses in the F1 mice, whereas NZW mice show no obvious abnormal phenotype. In the current study, we evaluated the impact of ROS, which is elevated by SOD1 deficiency, on the latent abnormality in the immune system of the NZW mice. We analyzed SOD1+/−/NZW male mice from viewpoints of fecundity, spermatogenesis, and immune responses. Breeding SOD1+/−/NZW male mice with SOD1+/+/NZW or SOD1+/+/ICR female mice also did not give birth any SOD1+/− mice. SOD1+/−/NZW male mice showed significant reduction in the testis weight and sperm count and significant increase in the number of morphologically abnormal seminiferous tubules in testes. We also found that the plasma IgG autoantibodies reactive to testicular proteins were elevated in the SOD1+/−/NZW mice. Oxidative stress marker in the testis was increased in the SOD1+/−/NZW mice. These results collectively provide notion that the oxidative stress caused by SOD1 haploinsufficiency exerts deleterious effects on the testis via activation of the autoimmune response in SOD1+/−/NZW male mice.