Health
Protein delivery to the testis restores male fertility in mice
According to the Mayo Clinic, about 15% of couples have infertility, and male infertility plays a role in more than one-third of these cases. Often the problem with sperm development is to blame.Now the researchers ACS Nano We have found a way to deliver proteins important for sperm cell production directly to the testis of mice. There, normal sperm development was restored and previously infertile mice could be delivered to their father’s puppies.
Male infertility is often caused by a lack of sperm in the semen, which can result from damage to the blood-testis barrier (BTB). This barrier protects germ cells from harmful toxins and drugs, and a protein called PIN1 is important for its function. Mice genetically engineered to lack PIN1 are infertile, have small testes, depleted sperm stem cells, and have low sperm counts.
Scientists have considered gene therapy to treat male infertility, but these procedures are dangerous because they can cause unwanted genetic alterations in germ cells that can be passed on to offspring. Hyun-Mo Ryoo et al. Wanted to develop a system that delivers proteins (such as PIN1) to the testis instead of genes, but first, they wanted to develop a method for incorporating proteins into cells through complex tubes in the testis. I had to find it.
Researchers have developed a delivery system called Fibroplex, which consists of spherical nanoparticles made of silk fibroin and a lipid coating. They loaded PIN1 into the Fibroplex and showed that the particles looked safe and showed no signs of toxicity or testicular damage in the mice. When the team injected the PIN1-loaded Fibroplex into the testes of young mice with a PIN1 deletion, treatment restored near-normal PIN1 levels and sperm stem cell counts and repaired BTB.
The treated mice had normal testis weight and size, and about 50% of the sperm count of wild-type mice. Up to about 5 months after treatment, when the protein was degraded, PIN1-Fibroplex-treated mice gave birth to as many offspring as wild-type mice, but untreated mice with a PIN1 deletion remained infertile. This is the first demonstration of direct delivery of protein to the testes to treat male infertility, the researchers say.
Source:
Journal reference:
Kim, WJ, et al. (2020) Intratesticular peptidyl prolyl isomerase 1 protein delivery using a cationic lipid-coated fibroin nanoparticle complex rescues male infertility in mice. ACS nano. doi.org/10.1021/acsnano.0c04936..
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