Silver nanoparticles stop sperm stem cell growth.

Sep 01, 2010

Braydich-Stolle, LK, B Lucas, A Schrand, RC Murdock, T Lee, J Schlager, S Hussain, and M-C Hofmann. 2010. Silver nanoparticles disrupt GDNF/Fyn kinase signaling in spermatogonial stem cells. Toxicological Scences http://dx.doi.org/10.1093/toxsci/kfq148.

Synopsis by Jennifer F. Nyland

A new study has identified exactly how silver nanoparticles cause male reproductive cells to stop growing.

Minute materials used in a number of consumer products such as antimicrobial agents can interrupt important cell signaling within male reproductive sperm cells, causing them to stop growing, according to a new study that builds on previous work by the same research group.

In prior studies, the scientists reported how smaller-sized silver nanoparticles – in the 10 - 25 nanometer range – decreased the growth of male stem cells when they were exposed at concentrations greater than 10 micrograms per milliliter (μg/ml).

The new study is the first to identify how the silver nanoparticles stop the sperm stem cells from growing. The biggest effects were caused by the smallest-sized nanoparticles tested.

This study raises important questions about potential effects on male fertility, because silver nanoparticles are currently used in a wide range of products.

In addition, exposure during development may affect forming sperm cells and lead to birth defects related to the male reproductive system. Scientists believe this is because the small silver particles can cross the mother's placenta and directly affect the baby.

Silver has long been recognized as a powerful antimicrobial. As such, the use of silver nanoparticles – ultra-small particles with diameters less than 100 nanometers – as antimicrobial coatings for clothing and bandages has boomed. Air sanitizers and personal care products also contain the nanoparticles.

Little information is available about how their widespread use translates into actual human exposures. Most likely, people breathe, eat or absorb them, especially if they manufacture or work with them. Consumer products may be another source. A growing number of studies find the silver particles do not remain in the products in which they are incorporated. They can migrate out of clothing and into artificial sweat (Correction, 9/2/10: that was used in the study to simulate perspiration). During washing, the silver can leach into the washwater and be carried by wastewater into the environment.

Health effects are even less understood, but studies to date have led experts to raise concerns. Because of their small size, nanoparticles can easily travel through the bloodstream and reach tissues – including the testes – after being inhaled or via other exposure pathways.

Previous laboratory studies show the silver nanoparticles are toxic to different types of cells, including lung, nerve and skin cells. They are also able to cross into the brain and travel through the blood to other body tissues. Some types of nanoparticles can cross the placenta, both human and animal studies show.

Spermatogenesis is the complex process in the testes that ultimately produces sperm. Environmental agents that slow the growth and proliferation of these cells may cause low sperm numbers and impact male fertility.

Using a cell line of mouse sperm stem cells, the researchers tested the effects of different sizes, concentrations and coatings of silver nanoparticles on cell growth. They compared silver nanoparticles coated with either hydrocarbons – at 15 nm, 25 nm and 80 nm diameters – or sugars – at 10 nm, 25 - 30 nm and 80 nm diameter.

Exposure to the smaller sized particles led to increased stem cell death. The coatings were important, too. The sugar coatings on the smaller-sized silver nanoparticles increased the production of reactive oxygen species (ROS), one of the signals for induced cell death.

One pathway known to be important for sperm stem cell growth is the growth factor glial cell line-derived neurotrophic factor (GDNF). The researchers found that while the amount of GDNF was not changed, the signals sent to the cell were damaged after silver nanoparticle exposure. Upon a closer look, they found that a small protein, Fyn kinase, was not fully functional. This protein requires a modification in order to function, and that modification was reduced when cells were exposed to silver nanoparticles.

An important limitation for this study is the lack of information on how the concentrations of silver nanoparticles used in this study relate to human exposures. Further, it is unclear whether these concentrations would be achieved within the testes.