Potential toxicity of engineered nanoparticles in mammalian germ cells and developing embryos: treatment strategies and anticipated applications of nanoparticles in gene delivery

Abstract

Background: Engineered nanoparticles (ENPs) offer technological advantages for a variety of industrial and consumer products as well as show promise for biomedical applications. Recent progress in the field of nanotechnology has led to increased exposure to nanoparticles by humans. To date, little is known about the adverse effects of these ENPs on reproductive health, although interest in nanotechnology area is growing. A few biocompatible ENPs have a high loading capacity for exogenous substances, including drugs, DNA or proteins, and can selectively deliver molecular cargo into cells; however, they represent a potential tool for gene delivery into gametes and embryos.

Objective and rationale: Understanding the reprotoxicological aspects of these ENPs is of the utmost importance to reliably estimate its potential impact on human health. In addition, a search for protective agents to combat ENP-mediated reproductive toxicity is warranted. Therefore, in this review we summarize the toxic effects of a few ENPs (metal and metal oxides, carbon-based nanoparticles, quantum dots and chitosan) in mammalian germ cells and developing embryos, and propose some treatment strategies that could mitigate nanoparticle-mediated toxicity. In addition, we outline the anticipated applications of ENPs in transgenic animal production in order to generate models for investigations into the mechanisms for human disease.

Search methods: A literature search was performed using the National Center for Biotechnology Information PubMed database up until March 2016 and relevant keywords were used to obtain information regarding mammalian germ cell-specific toxicity and embryotoxicity of ENPs, possible treatment strategies, as well as the anticipated applications of nanoparticles in gene delivery in germ cells and embryos. Only English language publications were included.

Outcomes: Here, we demonstrate the toxicological effects of ENPs in mammalian germ cells and developing embryos by considering both in vitro and in vivo experimental models based on the existing literature. The biodistribution and cellular uptake of ENPs and the observed toxicities are mostly dependent on ENP size and surface-coating agents (surface functional groups/surface charge). ENPs have been shown to induce toxicity via oxidative stress, inflammation and DNA damage in both human and mouse germ cells. Use of antioxidant, anti-inflammatory drugs and selective metal chelators would be beneficial against nanoparticle-induced toxicity.

Wider implications: Our review provides the reproductive scientists a mechanistic insight into the reprotoxicological aspects of ENPs to reliably estimate its potential impact on human health and help to select/design protective agents to combat ENP-mediated toxicity. Furthermore, research regarding the detailed mechanism(s) of ENP toxicity in mammalian germ cells and developing embryos as well as the search for protective agents to combat ENP-mediated reproductive toxicity is warranted. Furthermore, we anticipate that investigations into the possibility of applying nanovectors to gene delivery in germ cells and early embryos will open new horizons in reproductive biology.

Keywords: antioxidants; embryotoxicity; gene transfer; germ cell toxicity; nanoparticles; reactive oxygen species.