mRNA restores fertility in mice with genetic infertility

mRNA therapy restored fertility in mice with genetic infertility by reactivating sperm production.The treatment allows us to obtain healthy offspring, and the effects last for months, even a lifetime.There are safety challenges before applying it to humans....

The Japanese team succeeded in reviving sperm production in sterile mice by injecting Messenger RNA into the veins.The results last for months and can be maintained for life, allowing for healthy offspring.The researchers warned of significant safety challenges before considering clinical applications.

Messenger RNA (mRNA) technology, used in the development of Covid-19 vaccines, is being studied for many medical applications.Many groups have used the drug to prevent pregnancy complications such as preeclampsia.Allergy treatment alone;Or it's already being investigated to temporarily rejuvenate the immune system of old mice.Now research shows that it can also help restore male fertility caused by genetic disorders.

A team led by Takashi Shinohara, from Kyoto University (Japan), managed to restore sperm production and fertility in genetically infertile male mice by administering mRNA to the testes.The results are published today in Stem Cell Reports.

Infertility affects up to 10% of couples worldwide, according to World Health Organization estimates, and male factors are involved in about half of the cases.In many of these, the cause is a genetic abnormality that interferes with sperm production.

To solve this problem, the researchers developed a method aimed at introducing mRNA - a transient molecule that contains instructions for a gene - directly into the animal's sperm.They chose this strategy because the mRNA is quickly degraded and avoids permanent genetic changes in the cells.

The team first checked that the genetic material reached the main cell types of the testis, the germ cells that produce sperm and the Sertoli cells that support and regulate them.They then tested the technique in mice with a genetic defect in this latter cell that prevented spermatogenesis.This change is also associated with infertility and testicular disease in humans.

MRNA remained active for about two days, but the short-term boost was enough to open sperm production in animals. Using sperm obtained from treated mice, the researchers managed to obtain healthy offspring after dispersing mouse eggs using assisted reproductive techniques.

As Shinohara explained to SINC, the effects lasted much longer than he expected.“This works for a few months and probably the rest of your life,” he says.The professor of molecular genetics at Kyoto University believes that in some cases of infertility, it is sufficient to temporarily remove the barrier that prevents the production of sperm.

Despite the promising results, the researchers emphasize that there are significant safety issues.The main concern with the technique used to obtain offspring in experiments

After recovering the sperm cells from the treated animals, the researchers used microinsemination to fertilize the eggs."We recently discovered that microinsemination can cause behavioral abnormalities and birth defects in the offspring," explains Shinohara.

Microinsemination can cause behavioral abnormalities and birth defects in grandchildren.We have to monitor them very closely, including their behavior and life expectancy.

This technique is used to fertilize eggs after the gametes have been extracted.But researchers warn that there may be high risks. “I'm concerned because many people use micro-insemination to treat infertility,” he said. According to him, virtually every gene or RNA therapy tested in mice uses this procedure.

Even if offspring can be produced by natural mating in the future, the animals must be followed for a long period.“We have to monitor them closely, including their behavior and life expectancy,” he says.

The genetic defect has also been studied in some cases of human infertility.However, determining how many patients can benefit from a similar technique is complicated.

"It is not easy to establish a causal relationship with human infertility," admits Shinohara.However, the researchers believe that the principle may have a wider scope.

The work is also part of growing interest in mRNA-based therapies beyond vaccines.For Shinohara, however, the development of new reproductive technologies must be cautious.

New reproductive techniques should continue to be developed with caution.Extensive studies in animal models are an essential requirement before clinical application is considered.

"In general, reproductive methods are applied too quickly to humans without adequate testing in animals," he warns.For example,He used this method and cited intracytoplasmic sperm injection, which began to be used in humans only after four animals had been born.

In the researcher's opinion, extensive studies in animal models are an essential prerequisite before any clinical application can be considered.Still, he hopes the results will lead to new strategies for treating certain types of male infertility.

Takashi Shinohara et al. "Delivery of sern RNA to Sertoli cells restores fertility in infertile male mice".Stem Cell Reports, 2026.