Infertility is a problem faced by 1 in 6 couples worldwide. In half of the cases, the issue lies with the man. It is the failure to properly produce sperm. A joint team from Japan and the United States has demonstrated that the principle behind COVID vaccines can solve male infertility.
A joint research team from Osaka University in Japan and Baylor College of Medicine in the United States said on the 14th in the Proceedings of the National Academy of Sciences (PNAS) that "they delivered messenger ribonucleic acid (mRNA) to mice that could not produce sperm, achieving normal sperm production and even births."
The mice used in the experiment had nonobstructive azoospermia (NOA). It is a condition in which sperm are not produced in the testes due to a genetic defect. Human NOA patients are untreatable.
The team enabled the production of proteins necessary for making sperm in the testes of the mice. That does not mean they altered the mice's genes. Changing the genes of germ cells can pass the changes to offspring and cause problems.
An organism's genetic information is contained in DNA. A portion of it is copied into mRNA and used for protein synthesis. Instead of altering DNA, the researchers delivered mRNA—effectively a set of instructions for protein synthesis—to testicular cells to restore spermatogenesis. It is the same principle as the technology used in vaccines for the novel coronavirus disease (COVID-19).
Like COVID vaccines, the team encapsulated mRNA carrying the information to synthesize proteins needed for sperm production in lipid nanoparticles (LNPs) and delivered it. The mRNA carried by LNPs substituted for the function of genes required for spermatogenesis, helping cells in the testes resume division and maturation.
As a result, in mice where sperm formation had been halted by a genetic defect, precursor cells to sperm appeared after two weeks. Actual sperm were produced after three weeks. Using these sperm, the team performed intracytoplasmic fertilization and obtained 117 embryos, of which 26 were born as healthy pups. The pups grew normally, maintained fertility, and showed no genetic damage.
This study is the first case of restoring genetic infertility without directly editing damaged genes. Conventional gene therapy involves making direct changes to DNA, raising significant safety concerns, but mRNA therapy temporarily produces the needed proteins and is soon degraded, making it relatively safe.
In particular, the researchers attached a regulatory module to the mRNA to selectively activate only sperm cells. As a result, the mRNA functioned only in the germ cells that produce sperm and did not affect other cells.
Ikawa Masahito, a professor at Osaka University who led the study, said, "Using synthetic LNPs and mRNA, we can restore sperm production without altering the genome."
Martin M. Matzuk, a co-researcher and professor at Baylor College of Medicine, also said, "We have identified a concrete mechanism to revive spermatogenesis and laid the groundwork for future applications in treating hereditary infertility in humans."
References
PNAS (2025), DOI: https://doi.org/10.1073/pnas.2516573122