Mechanisms underlying reproductive toxicity induced by nickel nanoparticles identified by comprehensive gene expression analysis in GC-1 spg cells

• Published in: Environmental pollution (1987) 2021-04, Vol.275, p.116556, Article 116556
• Main Authors: Kong, Lu, Wu, Yongya, Hu, Wangcheng, Liu, Lin, Xue, Yuying, Liang, Geyu
• Format: Article
• Language: English
• Subjects: Acetates; Animals; Apoptosis; Cell transfection; Differentially expressed gene; Gene Expression; Male; Mice; Nanoparticles; Nickel - toxicity; Nickel nanoparticle; Phenols; Phosphatidylinositol 3-Kinases; piRNA; Proto-Oncogene Proteins c-akt; Reproductive toxicity
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2021.116556

The public around the world is increasingly concerned about male reproductive health. The impact of nickel nanoparticles (Ni NPs) on male reproductive toxicity including sperm production, motility and fertilizing capacity has been confirmed by our previous researches. In the current study of Ni NPs-inducing toxicity, the expression profiles of piRNAs and their predicted target genes associated with male infertility, were obtained. The results showed that piR-mmu-32362259 was the highest differential expression multiples in both the testis tissues of male mice and GC-1 cells similarly. Notably, piR-mmu-32362259 target gene was significantly enriched in the PI3K-AKT signaling pathway. All these results suggest that piR-mmu-32362259 may affect the occurrence and development of injury in the mouse spermatogenesis process by regulating the PI3K-AKT signaling pathway. In order to verify the result, piR-mmu-32362259 low-expression lentivirus was used to transfect GC-1 cells to establish a stable transfected cell model. The effects of piR-mmu-32362259 on the viability, cycle and apoptosis as well as related protein expression levels of GC-1 cells induced by Ni NPs were detected using CCK8, flow cytometry and western blot assay, respectively. The results showed that low expression of piR-mmu-32362259 could not only alleviate the decrease of GC-1 cell viability, affect the cell cycle and reduce the apoptosis rate, but also significantly affect the expression levels of key proteins and their downstream molecules of PI3K/AKT/mTOR signaling pathway. Collectively, our current results provide a theoretical basis for further exploring the molecular regulatory mechanism of male reproductive toxicity induced by Ni NPs. [Display omitted] •Nickel nanoparticles are known to cause male reproductive toxicity.•PIRNA is important in the reproductive toxicity induced by nickel nanoparticles.•PiR-mmu-32362259 may affect the process of sperm damage in mice.•Low expression of piR-mmu-32362259 could affect the state of GC-1 cells.•PiR-mmu-32362259 could regulate the expression of PI3K-AKT pathway related proteins. PiR-mmu-32362259 could significantly enhance Ni NPs-induced GC-1 cell damage by suppressing PI3K/AKT/mTOR signaling pathway, which is of great significance for the protection of reproductive health and formulating safety evaluation criteria of nanomaterials.