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Promoting Drp1-Mediated Mitochondrial Division in Nickel Nanoparticles-Induced Reproductive Toxicity in GC-2 Cells
Liya Qiao1, Zhimin Tong2, Yabing Xu1
1Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Abstract:
Male reproductive disorders and declining fertility rates play an important role in birth rates, and their impact on future populations makes them one of the most serious public health issues of this century. Defects in spermatogenesis are the most common manifestation of male infertility, and exposure to environmental pollutants has been suggested as a potential cause. Nanomaterials, due to their unique physicochemical properties and widespread application, have raised growing concerns about their potential reproductive toxicity. Studies have shown that nickel nanoparticles (Ni NPs) have reproductive toxicity in male rats and mice, especially sperm damage. This study aimed to explore the male reproductive toxicity of Ni NPs and the role of mitochondrial fission in mouse spermatocytes (GC-2). Our results showed that Ni NPs induced the damage of mitochondrial structure and function in GC-2 cells and disrupted intramitochondrial homeostasis, thereby resulting in enhanced Dynamin-related protein 1(Drp1)-mediated mitochondrial fission and cell apoptosis, along with aggravated cytotoxicity and obvious reproductive toxicity. The mitochondrial division inhibitor 1(Mdivi-1) and lentiviral-transfected low expression of Dnm1l can significantly alleviate the germ cell toxicity caused by Ni NPs, suggesting a certain therapeutic effect. The novelty of this study lies in its systematic demonstration that Drp1-mediated mitochondrial division is a core pathogenic mechanism of Ni NP-induced male reproductive toxicity, and the validation of both pharmacological inhibition and genetic silencing as effective intervention strategies. Therefore, this study offers a reference for expanding the reproductive toxicity effect of Ni NPs and potential molecular mechanisms and provides an important basis for finding potential targets and treatment of Ni NPs.
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