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

Reprod Toxicol. 2016 Aug;63:169-73. doi: 10.1016/j.reprotox.2016.06.008. Epub 2016 Jun 16.

Abstract

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.

Keywords: Ataxia Telangiectasia Mutated; DNA damage; Glucose-6-phosphate dehydrogenase; Glutathione; Oxidative stress; Testis.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Comet Assay
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Genotype
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione / metabolism*
  • Male
  • Mice
  • Mutation
  • Oxidation-Reduction
  • Oxidative Stress
  • Spermatozoa / metabolism*
  • Testis / metabolism*

Substances

  • 8-Hydroxy-2'-Deoxyguanosine
  • Glucosephosphate Dehydrogenase
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Deoxyguanosine
  • Glutathione