Effects of Aging and Oxidative Stress on Spermatozoa of Superoxide-Dismutase 1- and Catalase-Null Mice

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

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Neuroprotection by Manganese Superoxide Dismutase (MnSOD) Mimics: Antioxidant Effect and Oxidative Stress Regulation in Acute Experimental Stroke

CNS Neuroscience & Therapeutics ◽

10.1111/j.1755-5949.2012.00380.x ◽

2012 ◽

Vol 18 (10) ◽

pp. 811-818 ◽

Cited By ~ 34

Author(s):

Hai-Feng Huang ◽

Fei Guo ◽

Yuan-Zhao Cao ◽

Wen Shi ◽

Qing Xia

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Manganese Superoxide Dismutase ◽

Antioxidant Effect ◽

Experimental Stroke ◽

Stress Regulation ◽

Manganese Superoxide ◽

And Oxidative Stress

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The Exacerbation of Aging and Oxidative Stress in the Epididymis of Sod1 Null Mice

Antioxidants ◽

10.3390/antiox9020151 ◽

2020 ◽

Vol 9 (2) ◽

pp. 151 ◽

Cited By ~ 3

Author(s):

Anaīs Noblanc ◽

Alicia Klaassen ◽

Bernard Robaire

Keyword(s):

Oxidative Damage ◽

Oxygen Species ◽

Superoxide Dismutase 1 ◽

Free Radical Theory ◽

Radical Theory ◽

Theory Of Aging ◽

Accumulation Of Damage ◽

Effects Of Aging ◽

And Oxidative Stress

There is growing evidence that the quality of spermatozoa decreases with age and that children of older fathers have a higher incidence of birth defects and genetic mutations. The free radical theory of aging proposes that changes with aging are due to the accumulation of damage induced by exposure to excess reactive oxygen species. We showed previously that absence of the superoxide dismutase 1 (Sod1) antioxidant gene results in impaired mechanisms of repairing DNA damage in the testis in young Sod1−/− mice. In this study, we examined the effects of aging and the Sod−/− mutation on mice epididymal histology and the expression of markers of oxidative damage. We found that both oxidative nucleic acid damage (via 8-hydroxyguanosine) and lipid peroxidation (via 4-hydroxynonenal) increased with age and in Sod1−/− mice. These findings indicate that lack of SOD1 results in an exacerbation of the oxidative damage accumulation-related aging phenotype.

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