Does Ataxia Telangiectasia Mutated (ATM) protect testicular and germ cell DNA integrity by regulating the redox status?

- The redox status in mice that carry at least one Atm-ΔSRI allele, reflected by glutathione levels and antioxidant capacity, was lower than in wild type mice.
- Glucose-6-phosphate dehydrogenase activity was higher in mice that were homozygous for Atm-ΔSRI when compared to heterozygous mice.
- Oxidative DNA damage in testis and sperm was increased in mice that carried the Atm-ΔSRI allele.
- Defective Atm reduces redox homeostasis of the testis and genetic integrity of sperm by regulating glutathione levels.

A balanced redox homeostasis in the testis is essential for genetic integrity of sperm. Reactive oxygen species can disturb this balance by oxidation of glutathione, which is regenerated using NADPH, formed by glucose-6-phosphate dehydrogenase (G6PDH). G6PDH is regulated by the Ataxia Telangiectasia Mutated (Atm) protein. Therefore, we studied the redox status and DNA damage in testes and sperm of mice that carried a deletion in Atm. The redox status in heterozygote mice, reflected by glutathione levels and antioxidant capacity, was lower than in wild type mice, and in homozygotes the redox status was even lower. The redox status correlated with oxidative DNA damage that was highest in mice that carried Atm deletions. Surprisingly, G6PDH activity was highest in homozygotes carrying the deletion. These data indicate that defective Atm reduces the redox homeostasis of the testis and genetic integrity of sperm by regulating glutathione levels independently from G6PDH activity.