Exposure effects of inhaled nickel nanoparticles on the male reproductive system via mitochondria damage
Graphical abstract
Introduction
Nowadays, with the rapid development of nanotechnology, applications of engineering nanomaterials in many areas of human endeavors make nanoparticles enter the environment constantly when released from products containing them. Once the nanoparticles enter the living body, they can cause special biological effects owing to their volume effect, quantum size effect, controlled surface effect and macroscopic quantum tunneling effect, consequently posing enormous threat to living organisms (Ju-Nam and Lead, 2008). Therefore, the potential negative impacts of engineering nanomaterials on human health and living environment have attracted worldwide attention.
Except for the properties of nanoparticles themselves, nickel nanoparticles (Ni NPs), a new type of metal material, also has extraneous other features, including magnetic, electrical, optical and mechanical aspects, which make them play a key role in many research fields such as biological medicine, metallurgy, electronics, information, aerospace and chemical industry (Abdulqadir and Aziz, 2019; Derevianko et al., 2020). The widespread use of Ni NPs increases its concentration in biogeochemical cycles and enhances human exposure to it and its compounds through environmental contamination and occupational exposure (Levine et al., 2017). Especially in the field of biomedicine, Ni NPs can be used for biological probes, isolation of DNA from the total protein, targeted drug delivery, hyperheat treatment of malignant tumor cells, contrast-enhanced magnetic resonance imaging, contrast-enhanced magnetic resonance imaging, and so on. As a high performance electrode material, nickel-metal hydride battery is superior to that produced by carbonyl nickel powder for its large capacity, small volume, light weight, safety, stability and high cost performance, which enabled its wide application in variety of fields in our lives. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation (Brohi et al., 2017). In the last decade, various studies have been reported on the hazards of exposure to Ni NPs that could induce pulmonary toxicity (Glista-Baker et al., 2014; Di Bucchianico et al., 2018; Mo et al., 2019), liver and spleen toxicity (Magaye et al., 2014a, Magaye et al., 2014b), cardiovascular toxicity (Kang et al., 2011), genotoxicity (Magaye and Zhao, 2012; Dumala et al., 2017), and spermiotoxicity (Gallo et al., 2016), even induce cancer (Magaye and Zhao, 2012; Magaye et al., 2012; Magaye et al., 2014a, Magaye et al., 2014b). Recently, male reproductive health, one of the important problems caused by environmental pollution, has attracted more and more attention from many medical scientists and has become recent research hotspot in the environmental science, toxicology and epidemiology (Levine et al., 2017). Using an adult albino rat model, it has been confirmed that nanomaterials can easily cross the blood-testosterone barrier and cause germ cell damage due to their ultramicro-properties (Ahmed et al., 2017). Lately, there is accumulating evidence indicating that Ni NPs has reproductive and developmental toxicity (Gallo et al., 2016; Ispas et al., 2009; Zhou et al., 2016; Santos et al., 2017; Kanold et al., 2016). Similar to these documents, it has also been demonstrated in our previous studies that Ni NPs has reproductive toxicity on both rats and caenorhabditis elegans, in which the male reproductive system is more sensitive to Ni NPs than the female reproductive system (Kong et al., 2017; Kong et al., 2019). However, to date, the specific mechanism underlying the exposure of Ni NPs to reproductive toxicity is still unclear. More importantly, it has been documented that mitochondrial impairment could play a critical role in sperm abnormality, leydig cells' injury, and testis injury (Ommati et al., 2021) . Therefore, this study aims to study the effect of inhaled Ni NPs on male reproductive system and the possible mechanism responsible for the male reproductive toxicity in mice involving the mitochondrial fission and mitophagy.
Section snippets
Chemicals
Ni NPs with an average size of 90 nm (Product Code, FNiN-80; Black Powder, Purity, 99%; Surface area, ≥ 8 m2/g; Bulk density, 0.06–0.8 g/cm3) were purchased from Nano Science and Technology Co., Ltd. (Kunshan-miyou, Kunshan, China). Micron nickel particles (Ni MPs) with an average size of 3 μm (Product Code: ST-M-008-2; Gray-black powder, Purity: 99.0%, Surface area ≥ 3 m2/g) were purchased from Material Technology Co., Ltd. (Shanghai, China) and nickel(II) chloride (NiCl2) were purchased from
Characterization of Ni NPs
The characterization of Ni NPs were seen in Fig. 1. But the results has been reported in detail in our previous experimental study (Kong et al., 2014; Kong et al., 2017).
Effect of inhaled Ni NPs on body weight and testicular organ coefficient in mice
After intratracheal instillation of different dose of Ni NPs, the body weight of mice increased gradually within 28 days in the control group and different dose of Ni NPs groups. As compared with control group and low dose group, the body weight of mice in middle and high dose groups was slightly lower, but there was no
Discussion
An epidemiological survey of occupational nickel exposure and workers' health status conducted ten years ago reported a case of inadvertent occupational exposure in a previously healthy young man who died of respiratory distress syndrome 13 days after exposure to Ni NPs through the respiratory tract at work, and the presence of Ni NPs was detected in his lungs, urine and kidneys (Phillips et al., 2010). In particular, Ni NPs mainly cause health damage after entering the human system through
Conclusions
Our current studies confirm that inhalation of Ni NPs through intratracheal instillation can result in serious reproductive damage in male mice such as decreased serum reproductive hormones and sperm count, increased serum inflammatory factors, sperm deformities and cell apoptosis in testicular tissue, and pathological changes of mouse testis. Importantly, mitochondrial fission and mitophagy are both involved in this toxic process. Collectively, mitochondria damage may play an important role in
Declaration of Competing Interest
The authors declare that all authors have no competing interests related to the manuscript.
Acknowledgments
The authors thank the support from the National Natural Science Funds of China (NSFC, No. 81502783, 21876026 and 31671034).
References (36)
- et al.
Uptake of PMMA nanoparticles from the gastrointestinal tract after oral administration to rats: modification of the body distribution after suspension in surfactant solutions and in oil vehicles
Int. J. Pharm.
(1999) - et al.
Manufactured nanoparticles: an overview of their chemistry, interactions and potential environmental implications
Sci. Total Environ.
(2008) - et al.
Metallic nickel nanoparticles and their effect on the embryonic development of the sea urchin Paracentrotus lividus
Environ. Pollut.
(2016) - et al.
Abnormal sperm development in pcd(3J)−/− mice: the importance of Agtpbp1 in spermatogenesis
Mol Cells
(2011) - et al.
Monosialic ganglioside GM3 specifically suppresses the monocyte adhesion to endothelial cells for inflammation
Int. J. Biochem. Cell Biol.
(2014) - et al.
Mechanisms underlying nickel nanoparticle induced reproductive toxicity and chemo-protective effects of vitamin C in male rats
Chemosphere
(2019) - et al.
Recent progress in studies of metallic nickel and nickel-based nanoparticles’ genotoxicity and carcinogenicity
Environ. Toxicol. Pharmacol.
(2012) - et al.
Toxicity of nickel in the marine calanoid copepod Acartia tonsa: nickel chloride versus nanoparticles
Aquat. Toxicol.
(2016) - et al.
Internalization and effects on cellular ultrastructure of nickel nanoparticles in rat kidneys
Int. J. Nanomedicine
(2019) - et al.
Evaluating the effect of silver nanoparticles on testes of adult albino rats (histological, immunohistochemical and biochemical study)
J. Mol. Histol.
(2017)
Inflammation and (secondary) genotoxicity of Ni and NiO nanoparticles
Nanotoxicology
Toxicity of nanoparticles on the reproductive system in animal models: a review
Front. Pharmacol.
The effect of reproductive toxicity induced by ZnO NPs in mice during early pregnancy through mitochondrial apoptotic pathway
Environ. Toxicol.
Biological activity of nickel nanoparticles
Agriciltural Microbiology
Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells
Part Fibre Toxicol
Genotoxicity study of nickel oxide nanoparticles in female Wistar rats after acute oral exposure
Mutagenesis
Biochemical alterations induced by nickel oxide nanoparticles in female Wistar albino rats after acute oral exposure
Biomarkers
Spermiotoxicity of nickel nanoparticles in the marine invertebrate Ciona intestinalis (ascidians)
Nanotoxicology
Cited by (9)
Toxicity mechanism of engineered nanomaterials: Focus on mitochondria
2024, Environmental PollutionBioinspired engineered nickel nanoparticles with multifunctional attributes for reproductive toxicity
2023, ChemosphereCitation Excerpt :Furthermore, the histological alterations in the reproductive organs of male rats after nickel oxide nanoparticles exposure were also noticed. In this study reduced spermatogenic cells and lumen with less number of sperms were observed in Ni-NPs exposed rats and these are in accordance with the work done by Kong et al. (2021), due to inhalation of Ni-NPs in rats. Silver nanoparticles induced hormonal disturbance and produced ROS in testicular cells caused histological alterations and abnormality in sperm (Olugbodi et al., 2020).
Nickel nanoparticles exert cytotoxic effects on trophoblast HTR-8/SVneo cells possibly via Nrf2/MAPK/caspase 3 pathway
2022, Environmental ResearchCitation Excerpt :In addition, several studies have suggested that Ni NPs have reproductive and developmental toxicity (Gallo et al., 2016; Kong et al., 2014, 2021). Recently, a research group reported that exposure to Ni NPs may be associated with male infertility, accompanied by the activation of the PI3K signalling axis (Kong et al., 2021). This group also found that exposure to Ni NPs causes inflammatory responses and cell apoptosis and alters the levels of several hormones that play vital roles in regulating the development of ovaries in rats (Kong et al., 2014).
Ni-Alginate Hydrogel Microspheres with Sustained Interleukin 2 Release to Boost Cytokine-Based Cancer Immunotherapy
2023, Advanced Functional Materials