Protein delivered to testes improves sperm production

Scientists have directly delivered proteins to mouse testes for the first time, in an attempt to treat male infertility.

The team of researchers from Seoul National University, South Korea, successfully delivered an important protein, necessary for sperm production, into the testes of infertile mice and restored normal reproductive function.

Infertility affects around 15 percent of couples worldwide, with male infertility thought to be linked to anywhere between 20-70 percent of these cases. Damage to the blood-testis barrier (BTB), which normally protects sperm cells from any harmful substances within the blood, is one cause of reduced sperm production.

Although gene therapy has the potential to correct defects underlying male infertility, there remains a number of safety and ethical concerns. The adverse long-term effects of genome editing of germ cells and risk to future generations remain unknown.

In the current study, published in ACS Nano, the scientists developed an alternative approach, using nanoparticles to directly deliver proteins to the testes. The delivery system, called Fibroplex, consisted of spherical nanoparticles made of silk fibroin, which were coated in lipids.

The Fibroplex was loaded with a protein required for normal function of the BTB, known as PIN1. The entire complex was then injected into the testes of young male mice which had been genetically engineered to lack the PIN1 protein, making them infertile.

The scientists found that Fibroplex safely delivered the PIN1 protein to the mouse testes and did not lead to any toxicity or testicular damage. The treatment increased sperm stem cell numbers and repaired the BTB. In addition, the treated mice had an increased number of mature sperm. Although the sperm count was still only around half of that of normal fertile mice, the treated mice were able to father a similar number of pups, whilst untreated PIN1-deficient mice were unable to reproduce.

The beneficial effects of the treatment lasted for approximately five months, after which the PIN1 protein degraded.

Further studies are now needed in order for scientists to understand whether this approach may be an effective strategy for treating infertility in humans.