Abstract：
:Activation of the unfolded protein response (UPR) in the endoplasmic reticulum (ER) and mitochondrial apoptotic pathway serves as a central regulator for maintaining cell function and survival, and is associated with ageing and spermatogenesis. However, changes in UPR activation and mitochondrial apoptotic pathway in the testis during ageing remain unclear. In this study, we hypothesized that UPR activation declines and the mitochondrial apoptotic pathway is activated in the testis during ageing, and these changes are associated with a decline in testicular function. To test this theory, we utilized 6-, 12-, 18-, and 22-month-old Sprague Dawley rats to evaluate the changes in testicular and epididymal weights and indexes, sperm quality, histology, UPR activation, and mitochondrial apoptotic pathway in testicular tissues. The results showed that there was a progressive decline in testicular and epididymal weights and indexes, sperm count, and sperm viability during ageing. Correspondingly, seminiferous tubule diameters and epithelium heights progressively decreased with ageing. Western blot analysis and immunofluorescence staining results revealed that the expression of UPR-related proteins (GRP78, p-PERK, p-eif2α, ATF4, p-IRE1α, ATF6α, and XBP1) progressively decreased in the testis with ageing. In contrast, the expression of ER stress-related pro-apoptotic proteins CHOP, Caspase 12, and p-JNK progressively increased with advancing age. TUNEL staining further confirmed that testicular germ cell apoptosis was significantly increased from month 6 to 22 in rats. Additionally, the relative expression levels of cytochrome c and its downstream molecules including Capsase 9 and Caspase 3 were significantly increased in the testis during ageing. Collectively, our results suggest that impaired UPR activation and increased germ cell apoptosis partly mediated by the UPR and mitochondrial apoptotic pathway might correlate with an age-related decline in testicular function.
journal_name
Exp Gerontoljournal_title
Experimental gerontologyauthors
Zhao H,Ma N,Chen Q,You X,Liu C,Wang T,Yuan D,Zhang Cdoi
10.1016/j.exger.2019.110721subject
Has Abstractpub_date
2019-11-01 00:00:00pages
110721eissn
0531-5565issn
1873-6815pii
S0531-5565(19)30138-Xjournal_volume
127pub_type
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journal_title：Experimental gerontology
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journal_title：Experimental gerontology
pub_type： 杂志文章,随机对照试验
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journal_title：Experimental gerontology
pub_type： 杂志文章
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journal_title：Experimental gerontology
pub_type： 杂志文章
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journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2015.04.012
更新日期：2015-07-01 00:00:00
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journal_title：Experimental gerontology
pub_type： 杂志文章,评审
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doi：10.1016/j.exger.2020.111104
更新日期：2020-12-01 00:00:00
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journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2007.04.010
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pub_type： 杂志文章,评审
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pub_type： 杂志文章,多中心研究
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doi：10.1016/j.exger.2016.12.003
更新日期：2017-02-01 00:00:00
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journal_title：Experimental gerontology
pub_type： 杂志文章,评审
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journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2017.03.017
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
doi：10.1016/j.exger.2005.04.007
更新日期：2005-07-01 00:00:00
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journal_title：Experimental gerontology
pub_type： 杂志文章
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更新日期：2003-05-01 00:00:00
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journal_title：Experimental gerontology
pub_type： 杂志文章
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更新日期：1996-11-01 00:00:00
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