TY - JOUR
T1 - Does Ataxia Telangiectasia Mutated (ATM) protect testicular and germ cell DNA integrity by regulating the redox status?
AU - Godschalk, Roger W. L.
AU - Vanhees, Kimberly
AU - Maas, Ludovicus
AU - Drittij - Reijnders, Marie Jose
AU - Pachen, Danielle
AU - van Doorn-Khosrovani, Sahar van Waalwijk
AU - van Schooten, Frederik J.
AU - Haenen, Guido R. M. M.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
KW - Ataxia Telangiectasia Mutated
KW - DNA damage
KW - Oxidative stress
KW - Testis
KW - Glutathione
KW - Glucose-6-phosphate dehydrogenase
U2 - 10.1016/j.reprotox.2016.06.008
DO - 10.1016/j.reprotox.2016.06.008
M3 - Article
C2 - 27318254
SN - 0890-6238
VL - 63
SP - 169
EP - 173
JO - Reproductive Toxicology
JF - Reproductive Toxicology
ER -