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7 June 2021 Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice
Paulina Nguyen-Powanda, Bernard Robaire
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Abstract

The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species 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 8-oxoguanine DNA glycosylase, a marker of base excision repair (BER), increased in aged WT and young Sod1–/– mice. In contrast, immunostaining intensity of DNA ligase 4 and RAD51 Recombinase, markers of nonhomologous 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.

Summary sentence

Aging and superoxide dismutase-1 knockout increase oxidative damage in mouse male germ cells with evidence of altered DNA repair mechanisms.

Graphical Abstract

© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Paulina Nguyen-Powanda and Bernard Robaire "Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice," Biology of Reproduction 105(4), 944-957, (7 June 2021). https://doi.org/10.1093/biolre/ioab114
Received: 6 April 2021; Accepted: 29 May 2021; Published: 7 June 2021
KEYWORDS
aging
male germ cells
oxidative stress
reactive oxygen species
spermatogenesis
superoxide dismutase-1
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