Gold nanorods injected into mice testes heat up when excited by a near-infrared laser, killing sperm cells and damaging sperm-generating cells. Stained cross-sections of testis tissue show the damage seven days after the treatment (right). As a comparison, tubules in a testis injected with saline solution remains intact, with sperm and sperm-generating cells filling the middle of the tubules (left). An average tubule is 200 µm wide.
Sun, Jun Wang, and their colleagues developed the new method based on the long-known fact that heating testis tissue kills sperm cells. To do the heating, they turned to rod-shaped gold nanoparticles, which absorb infrared light and convert it into heat. Other researchers are developing ways to use these particles to heat up and kill tumor cells.
Sun’s team envisioned heating up testis tissue to different temperatures for certain effects. They hypothesized that with a low heat, the nanorods would kill sperm cells but not sperm-producing cells, thus causing reversible contraception because the treatment would preserve the ability to produce sperm. But with a high heat, the particles would permanently damage sperm-producing cells, shutting down sperm production and leading to sterilization.
Compared to hormonal methods, Sun says, the nanorod technique would have few side effects because it does not disrupt other hormonal pathways in the body. Also, the method would be less invasive than a surgical procedure like vasectomy. While the approach could be developed for humans in the future, Sun says, it could be immediately applied to sterilize domestic animals.
As a test of the method, the researchers studied male mice in six groups. Animals in each group got a single testicular injection of one of three solutions: a saline solution, a 105 µM gold nanorod solution, or a 145 µM gold nanorod solution. The scientists then exposed the animals’ testes to near-infrared laser light at one of two power densities for about 10 minutes.
Using an infrared camera, the team found that the temperature of the mice’s testes hit between 37 and 45 °C, depending on the nanorod concentration and laser power. High concentrations and high powers lead to high temperatures. Normal mice testis tissue hovers around 29 °C.
As a fertility test, the researchers let the mice mate at seven and 60 days after treatment and calculated fertility as the percentage of pregnancies per total number of mated females. After seven days, mice that had experienced testes temperatures of 37 or 40 °C were 10% as fertile as untreated mice. Their fertility recovered to 50% at 60 days. Meanwhile, testes temperatures of 45 °C permanently sterilized the animals; all of their sperm-generating cells had died, and they produced no pups.
Diana L. Blithe, who runs a male contraception research program at the National Institute of Child Health and Human Development, says that to develop the method for people the team would need to ensure that the gold nanoparticles don’t migrate to other organs and that the laser irradiation is precisely targeted on the testes.
The method is appropriate for companion animals, says John K. Amory, a contraception researcher at the University of Washington, Seattle. But men may find it undesirable due to possible testicular pain during and after the injections. He says that long-term studies of the sterilization form of the technique will be important to ensure that the method is, in fact, permanent.