Cuproptosis mediates copper-induced testicular spermatogenic cell death  

作　　者：Jing-Yi Zhang Xu-Jun Yu Jun-Jun Li Yao Xiao Guang-Sen Li Fang Yang Liang Dong 

机构地区：[1]Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [2]Chengdu Fifth People’s Hospital,The Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 611130,China [3]TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China [4]Department of Surgery,The Reproductive and Women-Children Hospital,Chengdu University of Traditional Chinese Medicine,Chengdu 610041,China

出　　处：《Asian Journal of Andrology》2024年第3期295-301,共7页亚洲男性学杂志（英文版）

基　　金：supported by the National Natural Science Foundation ofChina(No.81973647 and No.82274325);the Chengdu Municipal HealthCommission(No.2023215).

摘　　要：Cuproptosis,a novel mechanism of programmed cell death,has not been fully explored in the context of spermatogenic cells.Thisstudy 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 withsodium chloride(control)or copper sulfate(CuSO_(4))at 50 mg kg^(−1),100 mg kg^(−1),or 200 mg kg^(−1),for 42 consecutive days.Micesubjected to copper overload exhibited a disruption in copper homeostasis.Additionally,significant upregulated expression of keycuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis.Immunohistochemicalanalysis revealed the presence of ferredoxin 1(Fdx1)in Sertoli cells,Leydig cells,and spermatogenic cells at various stages oftesticular development,and the Fdx1-positive staining area was significantly increased in copper-overloaded mice.Mitochondrialdysfunction and decreased adenosine triphosphate levels were also observed,further implicating mitochondrial damage undercuproptosis.Further analyses revealed pathological lesions and blood−testis barrier destruction in the testicular tissue,accompaniedby decreased sperm concentration and motility,in copper-overloaded mice.In summary,our results indicate that copper-overloadedmice 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 initialexperimental evidence for the occurrence of cuproptosis in the testis.

关 键 词：blood−testis barrier cuproptosis ferredoxin 1 spermatogenic cell death 

分 类 号：R394.8[医药卫生—医学遗传学]