Scientists delivered PIN1 protein into testicles and cured male infertility

According to Mayo Clinic, about 15% of pairs are infertile, and it is male infertility that causes it in almost a third of cases. Often, the problem is caused by the development of sperm cells. Researchers who report their discovery in a journal at ACS Nano have found a way to deliver protein, important for sperm production, directly to the testicles of mice. It restored sperm development in testicles and allowed previously infertile mice to continue their offspring.

Male infertility often occurs due to a lack of sperm in the seminal fluid. This can occur as a result of damage to the hemato-Testicular barrier. It is this barrier that protects the reproductive cells from harmful toxins and drugs, and PIN1 protein is essential for its functioning.

Scientists have raised mice by changing their genes, resulting in individuals with no PIN1. They were sterile, with small testicles, exhausted sperm stem cells and low sperm count. Although scientists have previously considered genetic methods to treat male infertility, such manipulations are dangerous. They can cause undesirable genetic changes in reproductive cells that can be passed on to offspring. Hyun-Mo Ryu from Seoul National University and his colleagues sought to develop a system to deliver proteins (such as PIN1) instead of genes to the testicles. However, at first they needed to find a way to deliver the right proteins through complex test channels to the cells.

The delivery of protein (red fluorescence) to the mice’ testes using a cationic lipid complex encapsulated with nanoparticles of fibroin (green) has restored male fertility. Submitted: adapted from ACS Nano 2020, DOI: 10.1021/acsnano.0c04936.

As a result, the researchers developed a unique delivery system called Fibroplex, which consisted of spherical nanoparticles made of silk fibroin and lipid cladding. They loaded PIN1 protein into the Fibroplex and found that the necessary particles are safe, do not show signs of toxicity and do not cause damage to the testicles in mice. When a team of scientists injected PIN1 into the testicles of young infertile mice, this treatment returned almost normal PIN1 levels, the number of sperm stem cells and restored the hemato-testinal barrier.

All mice treated had normal weight and testicle size. Approximately 5 months after treatment, the mice treated with PIN1-Fibroplex gave birth to the same number of calves as wild mice. Unprocessed mice with PIN1 deletions remained sterile.

The researchers said it was the first demonstration of direct protein delivery to the testicles to treat male infertility.