Prepubertal exposure to copper oxide nanoparticles induces Leydig cell injury with steroidogenesis disorders in mouse testes

作者全名："Zheng, Xiangqin; Chen, Jiadong; Kang, Lian; Wei, Yuexin; Wu, Yuhao; Hong, Yifan; Wang, Xia; Li, Dinggang; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde"

作者地址："[Zheng, Xiangqin; Chen, Jiadong; Kang, Lian; Wei, Yuexin; Wu, Yuhao; Hong, Yifan; Wang, Xia; Li, Dinggang; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China; [Zheng, Xiangqin; Chen, Jiadong; Kang, Lian; Wei, Yuexin; Wu, Yuhao; Hong, Yifan; Wang, Xia; Li, Dinggang; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing Key Lab Children Urogenital Dev & Tissue, Key Lab Child Dev & Disorders,Chongqing Key Lab Pe, Chongqing 400014, Peoples R China; [Wu, Shengde] Room 806,Kejiao Bldg 6,136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China; [Zheng, Xiangqin] Chongqing Med Univ, Childrens Hosp, Zhongshan 2nd Rd, Chongqing 400014, Peoples R China"

通信作者："Wu, SD (通讯作者)，Room 806,Kejiao Bldg 6,136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000964894400001

JCR分区：Q2

影响因子：3.1

年份：2023

卷号：654

期号：　

开始页：62

结束页：72

文献类型：Article

关键词：Copper oxide nanoparticles; Reproductive toxicity; Prepubertal testis; Leydig cells; Steroidogenesis; ERK1; 2 pathway

摘要："Copper oxide nanoparticles (CuONPs) are metallic multifunctional nanoparticles with good conductive, catalytic and antibacterial characteristics that have shown to cause reproductive dysfunction. However, the toxic effect and potential mechanisms of prepubertal exposure to CuONPs on male testicular development have not been clarified. In this study, healthy male C57BL/6 mice received 0,10, and 25 mg/ kg/d CuONPs by oral gavage for 2 weeks (postnatal day 22-35). The testicular weight was decreased, testicular histology was disturbed and the number of Leydig cells was reduced in all CuONPs-exposure groups. Transcriptome profiling suggested steroidogenesis was impaired after exposure to CuONPs. The steroidogenesis-related genes mRNA expression level, concentration of serum steroids hormones and the HSD17B3-, STAR-and CYP11A1-positive Leydig cell numbers were dramatically reduced. In vitro, we exposed TM3 Leydig cells to CuONPs. Bioinformatic analysis, flow cytometry analysis and western blotting analysis confirmed that CuONPs can dramatically reduce Leydig cells viability, enhance apoptosis, trigger cell cycle arrest and reduce cell testosterone levels. U0126 (ERK1/2 inhibitor) signifi-cantly reversed TM3 Leydig cells injury and testosterone level decrease induced by CuONPs. These outcomes indicate that CuONPs exposure activates the ERK1/2 signaling pathway, which further pro-motes apoptosis and cell cycle arrest in TM3 Leydig cells, and ultimately leads to Leydig cells injury and steroidogenesis disorders.(c) 2023 Elsevier Inc. All rights reserved."

基金机构："National Natural Science Foundation of China [82071632]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0069]"

基金资助正文："Funding This work was supported by the National Natural Science Foundation of China (No. 82071632) , Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0069) ."