Impact of Metal Nanoparticles on Germ Cell Viability and Functionality U Taylor 1 , A Barchanski 2 , W Kues 1 , S Barcikowski 3 and D Rath 1 1 Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, Mariensee, Germany; 2 Laser Zentrum Hannover e.V., Hannover, Germany; 3 Chair of Technical Chemistry I, University of Duisburg-Essen, Essen, Germany Contents Metal nanoparticles play an increasing role in consumer products, biomedical applications and in the work environ- ment. Therefore, the effects of nanomaterials need to be properly understood. This applies especially to their potential reproductive toxicology (nanoreprotoxicity), because any shortcomings in this regard would be reflected into the next generation. This review is an attempt to summarize the current knowledge regarding the effects of nanoparticles on reproduc- tive outcomes. A comprehensive collection of significant experimental nanoreprotoxicity data is presented, which high- light how the toxic effect of nanoparticles can be influenced, not only by the particles’ chemical composition, but also by particle size, surface modification, charge and to a consider- able extent on the experimental set-up. The period around conception is characterized by considerable cytological and molecular restructuring and is therefore particularly sensitive to disturbances. Nanoparticles are able to penetrate through biological barriers into reproductive tissue and at least can have an impact on sperm vitality and function as well as embryo development. Particularly, further investigations are urgently needed on the repetitively shown effect of the ubiqui- tously used titanium dioxide nanoparticles on the development of the nervous system. It is recommended that future research focuses more on the exact mechanism behind the observed effects, because such information would facilitate the produc- tion of nanoparticles with increased biocompatibility. Introduction The rapidly growing field of nanotechnology has created the potential for increasing nanoparticle exposure to humans. A multitude of new products containing such particles reaches the market every year, often without thorough toxicology tests (Oberdorster et al. 2005) or on product information. Many of them reach the consumer in the form of commercial products (Fig. 1a, Woodrow Wilson Database). A predominant category in this context is nanoparticles made from silver (Fig. 1b, Woodrow Wilson Database), which have been often reported to be cytotoxic (Johnston et al. 2010). These are followed by carbon, zinc, silica, titanium and gold nanoparticles. Another area, where nanoparticles are increasingly used, is in medical and biomedical research. In this regard, the main emphasis is on selective sensing (Wang and Ma 2009) and imaging of target molecules (Qian et al. 2008), localized cancer therapy by plasmonic heating of malignant tissue (Gannon et al. 2008) and delivery of effector molecules to specific receptors or target areas (Han et al. 2006). Contact with nanoparticles does not necessarily result from the use of nanoparticle products. The working environment can lead also to exposure to a considerable dose of nanoparticles, for example, airborne fumes released during welding of chromium–nickel-based steels (Antonini 2003). In general, thermal processing of metals releases airborne particles into the workplace that may cause adverse health effects. The processing of materials by laser, for example, releases a high fraction of nanoparticles (Barcikowski et al. 2007). Even con- ventional welding sets free particles with comparable high-specific surface area (Pohlmann et al. 2008). Apart from external sources, internal exposure to nanoparti- cles derived from mechanical wear of surgical implants (usually consisting of nickel ⁄ titanium or cobalt ⁄ chrome alloys) also exists (Brown et al. 2006; Case et al. 1994). The main sources and routes of exposure are summarized in Fig. 2. Compared with the corresponding bulk material, nanoscale particles are considerably more biologically active, which seems to derive mainly from their higher mass-specific surface area and is mirrored by a surface- specific dose–response (Faux et al. 2003; Oberdorster et al. 2005). The reasons suggested for cellular damage caused by nanoparticle exposure include production of reactive oxygen species (ROS; Oberdorster et al. 2005) and interaction with DNA (Singh et al. 2009). In somatic cells such insults cause inflammation or even malignant transformation. However, in case of germ line cells, either defect might lead to impaired fertility and ⁄ or congenital defects in the offspring. This hypothesis is supported by studies showing that male welders, especially those who work with stainless steel, have poorer sperm quality than those in other work. Moreover, an increase in either miscarriages or delayed conception was observed among welders and their spouses, compared with men in other professions (Antonini 2003). Consequently, it is sur- prising that there has been little more effort on studying the effects of nanoparticles on reproduction and on reproductively relevant cells and tissues. This review will mainly focus on the potential reproductive toxicology of metal nanoparticles (nano- reprotoxicity), because of their high abundance in consumer as well as biomedical products. Production of Metal Nanoparticles Nanoparticles are generally defined as separate particles between 1 and 100 nm in size (ASTM International). Their common generation states are solid powders, gaseous aerosols and colloidal dispersions in water or organic solvents, depending on preparation conditions and capping agents on the particle surface. Colloids are often preferred for use in research because of their safe and stable handling form, without the risk of particle inhalation. In the last two decades, a multiplicity of fabrication methods has been established for nanoparticle synthesis Reprod Dom Anim 47 (Suppl. 4), 359–368 (2012); doi: 10.1111/j.1439-0531.2012.02099.x ISSN 0936-6768 Ó 2012 Blackwell Verlag GmbH