Male infertility often occurs due to a lack of sperm in the seminal fluid. This could happen
Scientists raised mice by changing their genes, gettingas a result of individuals without PIN1. They were sterile, with small testes, depleted sperm stem cells, and low sperm count. Although scientists have previously considered gene treatments for male infertility, such manipulations are dangerous. They can cause unwanted genetic changes in reproductive cells that can be passed on to offspring. Hyun-Mo Ryu of Seoul National University and his colleagues aimed to develop a system to deliver proteins (such as PIN1) instead of genes to the testes. However, they first needed to find a way to get the right proteins through the complex channels of the testicles into the cells.
Protein delivery (red fluorescence) to testesmice using a cationic lipid complex encapsulated with fibroin nanoparticles (green) restored male fertility. Credit: Adapted fromACS Nano2020, DOI: 10.1021/acsnano.0c04936.
As a result, the researchers developed a uniquea delivery system called Fibroplex, which consisted of spherical nanoparticles of silk fibroin and a lipid shell. They loaded the PIN1 protein into Fibroplex and found that the required particles are safe, show no signs of toxicity, and do not damage the testicles in mice. When a team of scientists injected PIN1 into the testes of young, infertile mice, the treatment returned nearly normal PIN1 levels, sperm stem cell counts, and restored the blood-testicular barrier.
All treated mice were of normal weight andtesticle size. At approximately 5 months after treatment, mice treated with PIN1-Fibroplex gave birth to the same number of pups as wild-type mice. Untreated mice with PIN1 deletions remained infertile.
The researchers said this is the first demonstration of direct delivery of proteins to the testes for the treatment of male infertility.
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