Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process

Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor (GR) in the process. Methods Thirty-two male SD rats (4~6 weeks old, weighing 120~140 g) were randomly assigned into dimethyl sulfoxide (DMSO) group, mife...

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Main Authors: YANG Binwei, SUN Lei, LING Xi
Format: Article
Language:zho
Published: Editorial Office of Journal of Army Medical University 2024-12-01
Series:陆军军医大学学报
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Online Access:https://aammt.tmmu.edu.cn/html/202406014.htm
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author YANG Binwei
YANG Binwei
SUN Lei
LING Xi
author_facet YANG Binwei
YANG Binwei
SUN Lei
LING Xi
author_sort YANG Binwei
collection DOAJ
description Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor (GR) in the process. Methods Thirty-two male SD rats (4~6 weeks old, weighing 120~140 g) were randomly assigned into dimethyl sulfoxide (DMSO) group, mifepristone (RU486) group, chronic unpredictable mild stress (CUMS) group, and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d) was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS, mifepristone of 1 mg/(kg·d) was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling, the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis (CASA) system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone (CORT), sex hormones and inflammation factors.The contents of malondialdehyde (MDA), H2O2, NAD+/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of β-gal, p16, and GR in testicular tissue, and transmission electron microscopy was used to observe mitochondrial structure of spermatogenic cells. Results Compared with the DMSO group, the sperm density, serum levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were decreased while those of CORT and estradiol (E2) were increased in the CUMS group (all P < 0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group (all P < 0.05).And, ATP content and NAD+/NADH ratio were decreased while MDA and H2O2 levels were elevated in testicular tissues in the CUMS group (all P < 0.05).Moreover, the protein levels of testicular cell aging markers β-gal, p16 and GR were significantly enhanced in the CUMS group (all P < 0.01), accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicular β-gal, p16 and GR protein level (all P < 0.05). Conclusion Chronic psychological stress induces testicular damage in rats, presenting declines in sperm density and CORT level, which is possibly associated with GR-mediated cell senescence.
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spelling doaj-art-f47736a56bfd4e6dac1b158955ff937f2024-12-29T00:18:15ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272024-12-0146242698270610.16016/j.2097-0927.202406014Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the processYANG Binwei0YANG Binwei1SUN Lei2 LING Xi3Department of Toxicology, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038 Hechuan District Center for Disease Control and Prevention, Chongqing, 401520, ChinaDepartment of Toxicology, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038Department of Toxicology, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor (GR) in the process. Methods Thirty-two male SD rats (4~6 weeks old, weighing 120~140 g) were randomly assigned into dimethyl sulfoxide (DMSO) group, mifepristone (RU486) group, chronic unpredictable mild stress (CUMS) group, and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d) was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS, mifepristone of 1 mg/(kg·d) was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling, the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis (CASA) system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone (CORT), sex hormones and inflammation factors.The contents of malondialdehyde (MDA), H2O2, NAD+/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of β-gal, p16, and GR in testicular tissue, and transmission electron microscopy was used to observe mitochondrial structure of spermatogenic cells. Results Compared with the DMSO group, the sperm density, serum levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were decreased while those of CORT and estradiol (E2) were increased in the CUMS group (all P < 0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group (all P < 0.05).And, ATP content and NAD+/NADH ratio were decreased while MDA and H2O2 levels were elevated in testicular tissues in the CUMS group (all P < 0.05).Moreover, the protein levels of testicular cell aging markers β-gal, p16 and GR were significantly enhanced in the CUMS group (all P < 0.01), accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicular β-gal, p16 and GR protein level (all P < 0.05). Conclusion Chronic psychological stress induces testicular damage in rats, presenting declines in sperm density and CORT level, which is possibly associated with GR-mediated cell senescence. https://aammt.tmmu.edu.cn/html/202406014.htmchronic psychological stresschronic unpredictable mild stressreproductive damagecell senescenceglucocorticoid receptormitochondria
spellingShingle YANG Binwei
YANG Binwei
SUN Lei
LING Xi
Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
陆军军医大学学报
chronic psychological stress
chronic unpredictable mild stress
reproductive damage
cell senescence
glucocorticoid receptor
mitochondria
title Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
title_full Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
title_fullStr Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
title_full_unstemmed Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
title_short Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
title_sort effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
topic chronic psychological stress
chronic unpredictable mild stress
reproductive damage
cell senescence
glucocorticoid receptor
mitochondria
url https://aammt.tmmu.edu.cn/html/202406014.htm
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AT sunlei effectsofchronicpsychologicalstressontesticularcellsenescenceinratsandroleofglucocorticoidreceptorintheprocess
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