Exposure effects of inhaled nickel nanoparticles on the male reproductive system via mitochondria damage

Highlights

• Nickel nanoparticles are known to cause reproductive toxicity in male mice.

• The sperm deformity and cell apoptosis are both involved in this toxic process.

• Testicular spermatogenic cells were damaged by nickel nanoparticles.

• Testosterone, follicle stimulating hormone and luteinizing hormone increased.

• Mitochondria damage may play an important role in male reproductive toxicity.

Abstract

Nickel nanoparticles (Ni NPs) have a wide range of application prospects, however there is still a lack of their safety evaluation for the reproductive system. Nowadays, male reproductive health has been widely concerned for the increasing incidence of male infertility. To investigate the male reproductive toxicity induced by Ni NPs and its relation with the mitochondrial fission and mitophagy, male mice were administered with or without 5, 15, and 45 mg/kg of Ni NPs by intratracheal instillation. At the end of intervention, sex hormone level, sperm abnormality rate, pathological morphology of testis, cell apoptosis and the expression levels of Drp1, Pink1 and Parkin proteins in testis tissues were detected. The results indicated that the rate of sperm deformity and serum levels of reproductive hormones increased obviously with the increasing concentrations of Ni NPs. Testicular spermatogenic cells were damaged and the number of apoptotic cells increased significantly. Furthermore, the expressions of key proteins (Drp1, Pink1 and Parkin) related to mitochondrial fission/autophagy in testis tissues also increased after exposure to Ni NPs. Collectively, mitochondria damage may play an important role in male mice reproductive toxicity induced by the intratracheal instillation of Ni NPs.

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.