{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:48:36Z","timestamp":1788367716842,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>\n                    Cuproptosis, a novel mechanism of programmed cell death, has not been fully explored in the context of spermatogenic cells. This study investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper overload. Sixty male Institute of Cancer Research (ICR) mice were randomly divided into four groups that received daily oral gavage with sodium chloride (control) or copper sulfate (CuSO\n                    <jats:sub>4<\/jats:sub>\n                    ) at 50 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , 100 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , or 200 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , for 42 consecutive days. Mice subjected to copper overload exhibited a disruption in copper homeostasis. Additionally, significant upregulated expression of key cuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis. Immunohistochemical analysis revealed the presence of ferredoxin 1 (Fdx1) in Sertoli cells, Leydig cells, and spermatogenic cells at various stages of testicular development, and the Fdx1-positive staining area was significantly increased in copper-overloaded mice. Mitochondrial dysfunction and decreased adenosine triphosphate levels were also observed, further implicating mitochondrial damage under cuproptosis. Further analyses revealed pathological lesions and blood\u2212testis barrier destruction in the testicular tissue, accompanied by decreased sperm concentration and motility, in copper-overloaded mice. In summary, our results indicate that copper-overloaded mice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell death. These findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initial experimental evidence for the occurrence of cuproptosis in the testis.\n                  <\/jats:p>","DOI":"10.4103\/aja202383","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:02:06Z","timestamp":1706227326000},"page":"295-301","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Cuproptosis mediates copper-induced testicular spermatogenic cell death"],"prefix":"10.4103","volume":"26","author":[{"given":"Jing-Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Jun","family":"Yu","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Chengdu Fifth People\u2019s Hospital, The Fifth People\u2019s Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Sen","family":"Li","sequence":"additional","affiliation":[{"name":"TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Reproductive and Women-Children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Reproductive and Women-Children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"R1-20240829","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","article-title":"Necroptosis, pyroptosis and apoptosis: an intricate game of cell death","volume":"18","author":"Bertheloot","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"R2-20240829","doi-asserted-by":"crossref","first-page":"107158","DOI":"10.1016\/j.anireprosci.2022.107158","article-title":"Regulation of spermatogenic cell apoptosis by the pro-apoptotic proteins in the testicular tissues of mammalian and avian species","volume":"247","author":"Zakariah","year":"2022","journal-title":"Anim Reprod Sci"},{"key":"R3-20240829","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1095\/biolreprod.116.144063","article-title":"Regulatory effects of autophagy on spermatogenesis","volume":"96","author":"Yin","year":"2017","journal-title":"Biol Reprod"},{"key":"R4-20240829","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s10495-022-01733-0","article-title":"Several routes of cell death to secondary necrosis in the elasmobranch testis","volume":"27","author":"McClusky","year":"2022","journal-title":"Apoptosis"},{"key":"R5-20240829","doi-asserted-by":"crossref","first-page":"113556","DOI":"10.1016\/j.fct.2022.113556","article-title":"Dietary selenium excess affected spermatogenesis via DNA damage and telomere-related cell senescence and apoptosis in mice","volume":"171","author":"Zhang","year":"2023","journal-title":"Food Chem Toxicol"},{"key":"R6-20240829","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.biopha.2017.08.131","article-title":"The antineoplastic busulphan impairs peritubular and leydig cells, and vitamin B12 stimulates spermatogonia proliferation and prevents busulphan-induced germ cell death","volume":"95","author":"Sasso-Cerri","year":"2017","journal-title":"Biomed Pharmacother"},{"key":"R7-20240829","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"R8-20240829","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1530\/jrf.0.0320379","article-title":"Quantification of human seminiferous epithelium. 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