The dynamic changes of Nrf2 mediated oxidative stress, DNA damage and base excision repair in testis of rats during aging

氧化应激 DNA损伤 基底切除修复术 DNA修复 XRCC1型 生物 标记法 男科 细胞凋亡 生精小管 内分泌学 DNA 内科学 精子发生 遗传学 支持细胞 医学 基因 单核苷酸多态性 基因型
作者
Haixia Zhao,Laixin Song,Na Ma,Chaoqi Liu,Yaoyan Dun,Zhiyong Zhou,Ding Yuan,Changcheng Zhang
出处
期刊:Experimental Gerontology [Elsevier]
卷期号:152: 111460-111460 被引量:18
标识
DOI:10.1016/j.exger.2021.111460
摘要

Accumulation of oxidative stress, DNA damage and impaired DNA repair appear to play critical roles in the decline of testicular function with aging. However, when those factors begin to lose control in testis during aging has not yet been well understood. This study was designed to assess the changes of oxidative stress and DNA damage status, and DNA repair capacity in testis during aging. Thus, male Sprague-Dawley rats at 3, 9, 15 and 24 months of age were used to delineate the dynamic changes in testicular weight and index, testosterone concentration, testicular histology, Nrf2-mediated oxidative stress, DNA damage, DNA repair and apoptosis. Results showed that testicular weight and index, testosterone concentration and spermatid number progressively declined from 9 to 24 months of age. Similarly, seminiferous tubule diameters and seminiferous epithelium heights gradually diminished with aging. Nrf2-mediated antioxidant defense ability was significantly impaired in testis with increasing age including decreased the activity of SOD and the expression levels of Nrf2, HO-1 and NQO-1, and increased the contents of MDA. In addition, DNA damage including DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) also progressively increased accompanied by increased levels of 8-hydroxydeoxyguanosine (8-OHdG) and γ-H2AX, and activated ATM/Chk2 and ATR/Chk1 pathway. Consistent with the results of Nrf2 pathway, the expression levels of APE1, OGG1 and XRCC1 involved in base excision DNA repair (BER) pathway increased from 3 to 9 months of age, and then gradually decreased after 9 months of age. Finally, TUNEL and Western blot results further confirmed germ cell apoptosis progressively increased from 3 to 24 months of age as evidenced by decreased ratio of Bcl-2/Bax and levels of Bcl-2 expression, and increased Bax expression levels. Taken together, our results suggest that downregulation of antioxidant ability mediated by Nrf2 pathway and impairment of BER capacity might correlate with increased DNA damage, and then induce declining testicular function during aging after adult.
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