{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:43:03Z","timestamp":1787816583374,"version":"build-2784847793"},"reference-count":52,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81602890"],"award-info":[{"award-number":["81602890"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC1002001"],"award-info":[{"award-number":["2017YFC1002001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The negative association between psychological stress and male fertility has been known for many years. This study was aimed at (i) identifying spermatogenesis impairment induced by psychological stress in rats and (ii) exploring the role of glucocorticoid receptor (GR) signaling in these adverse effects (if they exist). Male Sprague Dawley rats were exposed to a six-week period of unpredictable chronic mild stress (uCMS) along with cotreatment of GR antagonist RU486 (1 mg\/kg\/day). Testicular damage was assessed by testicular pathological evaluation, epididymal sperm concentration, serum testosterone levels, testicular apoptotic cell measurements, and cell cycle progression analyses. Rats in the uCMS group had decreased levels of serum testosterone and decreased epididymal sperm concentration. The uCMS-treated rats also had decreased numbers of spermatids and increased levels of apoptotic seminiferous tubules; additionally, cell cycle progression of spermatogonia was arrested at the G0\/G1 phase. Furthermore, uCMS exposure caused an increase in serum corticosterone level and activated GR signaling in the testes including upregulated GR expression. RU486 treatment suppressed GR signaling and alleviated the damaging effects of stress, resulting in an increased epididymal sperm concentration. Overall, this work demonstrated for the first time that the activation of GR signaling mediates stress-induced spermatogenesis impairment and that this outcome is related to cell apoptosis and cell cycle arrest in germ cells.<\/jats:p>","DOI":"10.3390\/ijms20184470","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T10:52:26Z","timestamp":1568112746000},"page":"4470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Mechanisms of Stress-Induced Spermatogenesis Impairment in Male Rats Following Unpredictable Chronic Mild Stress (uCMS)"],"prefix":"10.3390","volume":"20","author":[{"given":"Peng","family":"Zou","sequence":"first","affiliation":[{"name":"Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, 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Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4108-7977","authenticated-orcid":false,"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niya","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third 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(1977). Other Factors Affecting Male Fertility, WB Saunders. Chapter 4."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.fertnstert.2015.09.016","article-title":"Psychological stress and testicular function: A cross-sectional study of 1215 Danish men","volume":"105","author":"Nordkap","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1093\/humrep\/17.12.3173","article-title":"Decline in sex ratio at birth after 10-day war in Slovenia: Brief communication","volume":"17","author":"Zorn","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1365-2605.2007.00806.x","article-title":"Psychological factors in male partners of infertile couples: Relationship with semen quality and early miscarriage","volume":"31","author":"Zorn","year":"2008","journal-title":"Int. J. Androl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21028","DOI":"10.3390\/ijms151121028","article-title":"Time-course changes of steroidogenic gene expression and steroidogenesis of rat Leydig cells after acute immobilization stress","volume":"15","author":"Lin","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3109\/19396368.2015.1030473","article-title":"Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress","volume":"61","year":"2015","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/humrep\/15.9.1917","article-title":"Apoptosis of testicular germ cells induced by exogenous glucocorticoid in rats","volume":"15","author":"Yazawa","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0303-7207(02)00290-3","article-title":"Mechanisms of glucocorticoid-induced Leydig cell apoptosis","volume":"199","author":"Gao","year":"2003","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/0018-506X(92)90005-G","article-title":"Role of glucocorticoids in the stress-induced suppression of testicular steroidogenesis in adult male rats","volume":"26","author":"Orr","year":"1992","journal-title":"Horm. Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.02.012","article-title":"The regulation of spermatogenesis by androgens","volume":"30","author":"Smith","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1210\/en.2013-1940","article-title":"In vivo actions of the Sertoli cell glucocorticoid receptor","volume":"155","author":"Hazra","year":"2014","journal-title":"Endocrinology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.physbeh.2015.03.017","article-title":"Restraint stress and social defeat: What they have in common","volume":"146","author":"Motta","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1439-0272.2009.00985.x","article-title":"Toxic effects of dexamethasone on mouse testicular germ cells","volume":"42","author":"Orazizadeh","year":"2010","journal-title":"Andrologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neubiorev.2018.12.002","article-title":"Chronic Unpredictable Mild Stress for Modeling Depression in Rodents:Meta-analysis of Model Reliability","volume":"99","author":"Antoniuk","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Novati, A., Yu-Taeger, L., Gonzalez Menendez, I., Quintanilla Martinez, L., and Nguyen, H.P. (2018). Sexual behavior and testis morphology in the BACHD rat model. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198338"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9599","DOI":"10.1038\/s41598-017-09943-2","article-title":"Melatonin ameliorates restraint stress-induced oxidative stress and apoptosis in testicular cells via NF-\u03baB\/iNOS and Nrf2\/ HO-1 signaling pathway","volume":"7","author":"Guo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-1-4614-4015-4_7","article-title":"Spermatogenesis","volume":"757","author":"Chu","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1136\/bmj.305.6854.609","article-title":"Evidence for decreasing quality of semen during past 50 years","volume":"305","author":"Carlsen","year":"1992","journal-title":"Bmj"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1097\/PSY.0000000000000595","article-title":"Semen Quality in Chinese College Students: Associations With Depression and Physical Activity in a Cross-Sectional Study","volume":"80","author":"Zou","year":"2018","journal-title":"Psychosom. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zou, P., Sun, L., Chen, Q., Zhang, G., Yang, W., Zeng, Y., Zhou, N., Li, Y., Liu, J., and Ao, L. (2018). Social support modifies an association between work stress and semen quality: Results from 384 Chinese male workers. J. Psychosom. Res.","DOI":"10.1016\/j.jpsychores.2018.10.013"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2016.04.009","article-title":"Spermatogenesis in humans and its affecting factors","volume":"59","author":"Neto","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1111\/ejn.12587","article-title":"Role of paraventricular nucleus-projecting norepinephrine\/epinephrine neurons in acute and chronic stress","volume":"39","author":"Flak","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5483\/BMBRep.2015.48.4.275","article-title":"Technical and clinical aspects of cortisol as a biochemical marker of chronic stress","volume":"48","author":"Lee","year":"2015","journal-title":"Bmb. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jri.2010.02.005","article-title":"Corticotropin-releasing hormone, stress and human reproduction: An update","volume":"85","author":"Kalantaridou","year":"2010","journal-title":"J. Reprod. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0143-4179(85)90021-6","article-title":"Naloxone reversal of stress-induced reproductive effects in the male rhesus monkey","volume":"5","author":"Gilbeau","year":"1985","journal-title":"Neuropeptides"},{"key":"ref_26","first-page":"P3","article-title":"Glucocorticoids inhibit kisspeptin neurons during stress-induced reproductive inhibition","volume":"32","author":"Wang","year":"2011","journal-title":"Endocr. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1038\/sj.ijo.0801281","article-title":"Synthesis and regulation of sex hormone-binding globulin in obesity","volume":"24","author":"Hautanen","year":"2000","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3109\/10253890.2011.585188","article-title":"Stress induces glucocorticoid-mediated apoptosis of rat Leydig cells in vivo","volume":"15","author":"Chen","year":"2012","journal-title":"Stress"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.steroids.2007.12.020","article-title":"Rapid mechanisms of glucocorticoid signaling in the Leydig cell","volume":"73","author":"Hu","year":"2008","journal-title":"Steroids"},{"key":"ref_30","first-page":"109","article-title":"Glucocorticoids, stress, and fertility","volume":"35","author":"Whirledge","year":"2010","journal-title":"Minerva Endocrinol."},{"key":"ref_31","first-page":"111","article-title":"The effects of glucocorticoids on bone cell metabolism and function","volume":"171","author":"Peck","year":"1984","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/cdd.2013.166","article-title":"Role of caspase-8 in thymus function","volume":"21","author":"Pozzesi","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.steroids.2016.05.012","article-title":"Effects of antenatal glucocorticoids on the developing brain","volume":"114","author":"Carson","year":"2016","journal-title":"Steroids"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0303-7207(93)90036-J","article-title":"Localization of the glucocorticoid receptor in testis and accessory sexual organs of male rat","volume":"95","author":"Schultz","year":"1993","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1530\/rep.1.00072","article-title":"Involvement of glucocorticoids in testicular involution after active immunization of boars against GnRH","volume":"127","author":"Wagner","year":"2004","journal-title":"Reproduction"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.med.48.1.129","article-title":"RU486 (mifepristone): Mechanisms of action and clinical uses","volume":"48","author":"Cadepond","year":"1997","journal-title":"Annu. Rev. Med."},{"key":"ref_37","first-page":"4602","article-title":"The effects of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture","volume":"36","author":"Lippman","year":"1976","journal-title":"Cancer Res."},{"key":"ref_38","first-page":"1121","article-title":"Glucocorticoids induce a G1\/G0 cell cycle arrest of Con8 rat mammary tumor cells that is synchronously reversed by steroid withdrawal or addition of transforming growth factor-alpha","volume":"7","author":"Goya","year":"1993","journal-title":"Mol. Endocrinol."},{"key":"ref_39","first-page":"131","article-title":"Effects of Maternal Dexamethasone Exposure During Lactation on Metabolic Imbalance and Oxidative Stress in the Liver of Male Offsprings of Wistar Rats","volume":"30","author":"Jeje","year":"2015","journal-title":"Niger. J. Physiol. Sci. Off. Publ. Physiol. Soc. Niger."},{"key":"ref_40","unstructured":"Nassar, G.N., and Leslie, S.W. (2019). Physiology, Testosterone. StatPearls, StatPearls Publishing LLC."},{"key":"ref_41","first-page":"101","article-title":"[Glucocorticoids receptors in rat testis: Their role in Leydig cells specific function and DNA synthesis (author\u2032s transl)]","volume":"37","author":"Evain","year":"1976","journal-title":"Ann. D\u2019endocrinologie"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.psyneuen.2017.03.018","article-title":"Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding","volume":"81","author":"Perfalk","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"ref_43","first-page":"257","article-title":"The role of hypothalamic-pituitary-gonadal hormones in the normal structure and functioning of the brain","volume":"62","author":"Atwood","year":"2005","journal-title":"Cell. Mol. Life Sci. Cmls"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1210\/en.2004-0732","article-title":"Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis","volume":"145","author":"Barreiro","year":"2004","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, N., Ma, H., Li, Z., Gao, Y., Cao, X., Jiang, Y., Zhou, Y., and Liu, S. (2017). Chronic unpredictable stress exacerbates surgery-induced sickness behavior and neuroinflammatory responses via glucocorticoids secretion in adult rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183077"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e207","DOI":"10.1038\/nutd.2016.14","article-title":"Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486","volume":"6","author":"Nagasawa","year":"2016","journal-title":"Nutr. Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.neuroscience.2014.12.048","article-title":"Chronic unpredictable mild stress decreases BDNF and NGF levels and Na+,K+-ATPase activity in the hippocampus and prefrontal cortex of mice: Antidepressant effect of chrysin","volume":"289","author":"Filho","year":"2015","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s002130050456","article-title":"Validity, reliability and utility of the chronic mild stress model of depression: A 10-year review and evaluation","volume":"134","author":"Willner","year":"1997","journal-title":"Psychopharmacology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Avolio, E., Fazzari, G., Zizza, M., De Lorenzo, A., Di Renzo, L., Alo, R., Facciolo, R.M., and Canonaco, M. (2018). Probiotics modify body weight together with anxiety states via pro-inflammatory factors in HFD-treated Syrian golden hamster. Behav. Brain Res.","DOI":"10.1016\/j.bbr.2018.09.010"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jep.2017.08.004","article-title":"Banxia-houpu decoction restores glucose intolerance in CUMS rats through improvement of insulin signaling and suppression of NLRP3 inflammasome activation in liver and brain","volume":"209","author":"Jia","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.neuropharm.2014.10.011","article-title":"Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress","volume":"89","author":"Luo","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_52","first-page":"1371","article-title":"[Isolation, purification and immunochemical characteristics of spermatogonia of rat]","volume":"86","author":"Ma","year":"2006","journal-title":"Zhonghua Yi Xue Za Zhi"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:18:35Z","timestamp":1760188715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,10]]},"references-count":52,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijms20184470"],"URL":"https:\/\/doi.org\/10.3390\/ijms20184470","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,10]]}}}