Scholarlink

<p>Nickel nanoparticles (Ni NPs) are widely used in industrial and commercial sectors, raising concerns about their potential occupational and environmental toxicity. Male infertility has increased significantly in recent decades, with environmental exposures playing a recognized role. Ni NPs have been identified as toxic agents that induce testicular damage and sperm abnormalities, yet their underlying molecular mechanisms are unknown. In this study, mouse spermatogonia GC-1 cells were used as an in vitro model to explore the role of mitochondrial autophagy (mitophagy) in the induced apoptosis of Ni NPs. Ni NPs significantly reduced cell viability, increased intracellular ROS levels, disrupted mitochondrial membrane potential, and triggered germ cell apoptosis. PINK1 and Parkin, key mitophagy-related proteins, exhibited significant upregulation. Cyclosporin A was used to inhibit mitophagy, attenuating mitochondrial damage and reducing apoptosis. In addition, <i>PINK1</i> knockdown achieved by lentiviral transfection confirmed its critical role in mediating Ni NPs-induced mitophagy and subsequent cell death. These findings demonstrate that overactivation of the PINK1/Parkin pathway promotes apoptosis to Ni NPs exposure by mitophagy. Our study provides new mechanistic insights into the role of mitophagy in reproductive damage caused by nanomaterials.</p> Graphical Abstract <p>Nickel nanoparticles induce mitochondrial dysfunction, oxidative stress, and apoptosis in GC-1 spermatogonia. Ni NPs activate excessive mitophagy through upregulation of the PINK1/Parkin pathway. Mitophagy inhibition by cyclosporin A alleviates mitochondrial damage and reduces apoptosis.<i>PINK1</i> knockdown confirms mitophagy as a key driver of Ni NPs-induced germ cell death.</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Overloaded mitochondrial stress drives reproductive damage in GC-1 mouse spermatogonia cells exposed to nickel nanoparticle

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月11日

查看全文
  • Lu Kong,
  • Geyu Liang,
  • Yán Wāng

摘要

Nickel nanoparticles (Ni NPs) are widely used in industrial and commercial sectors, raising concerns about their potential occupational and environmental toxicity. Male infertility has increased significantly in recent decades, with environmental exposures playing a recognized role. Ni NPs have been identified as toxic agents that induce testicular damage and sperm abnormalities, yet their underlying molecular mechanisms are unknown. In this study, mouse spermatogonia GC-1 cells were used as an in vitro model to explore the role of mitochondrial autophagy (mitophagy) in the induced apoptosis of Ni NPs. Ni NPs significantly reduced cell viability, increased intracellular ROS levels, disrupted mitochondrial membrane potential, and triggered germ cell apoptosis. PINK1 and Parkin, key mitophagy-related proteins, exhibited significant upregulation. Cyclosporin A was used to inhibit mitophagy, attenuating mitochondrial damage and reducing apoptosis. In addition, PINK1 knockdown achieved by lentiviral transfection confirmed its critical role in mediating Ni NPs-induced mitophagy and subsequent cell death. These findings demonstrate that overactivation of the PINK1/Parkin pathway promotes apoptosis to Ni NPs exposure by mitophagy. Our study provides new mechanistic insights into the role of mitophagy in reproductive damage caused by nanomaterials.

Graphical Abstract

Nickel nanoparticles induce mitochondrial dysfunction, oxidative stress, and apoptosis in GC-1 spermatogonia. Ni NPs activate excessive mitophagy through upregulation of the PINK1/Parkin pathway. Mitophagy inhibition by cyclosporin A alleviates mitochondrial damage and reduces apoptosis.PINK1 knockdown confirms mitophagy as a key driver of Ni NPs-induced germ cell death.