Testicles in a cryobank
The male macaque was castrated twice to get offspring from him
Polina Loseva, "The Attic"
His testicles were cut off, frozen, planted back, left to grow up, cut out a second time, fertilized with sperm a female – and a cub was born
In reproductive clinics, patients' germ cells are often frozen – for the future. But what if these cells haven't matured yet? Children with oncological diseases face such a situation. In order not to deprive them of the opportunity to produce offspring after recovery, doctors suggest castrating them and freezing the immature tissue of the testes. Then it can be implanted back so that it grows to the end. This technology was first fully tested on rhesus monkeys - from castration to the birth of a cub.
Germ cells can live in freezing for decades and remain functional – in case a person's own spermatozoa have already "aged" or died as a result of injury. This may be useful, for example, for patients with oncological diseases, since spermatogenic progenitor cells often die during antitumor therapy.
However, with boys with cancer, the situation is much more complicated: their testes are not yet mature enough to produce sperm, so it is pointless to freeze them. For such patients, doctors develop a more complex strategy – to remove the testicular tissue during treatment, and then plant it back so that it ripens inside the body.
This technology was tried on different animals: immature testicular tissue from mice, pigs and monkeys was transplanted under the skin of immunodeficient mice. Despite the differences between the donor and recipient, the tissue matured and produced spermatozoa that can fertilize an egg. In this regard, there was even an idea to plant seed tissue from sick people to animals so that it ripens in someone else's body. However, there is a risk of infection of cells with animal viruses, so it is better to grow testes inside a person.
Similar experiments have already worked on mice, but have not yet been successful on primates. Transplants did not take root well, and no one evaluated the quality of sperm. In the latest issue of Science, American and Canadian researchers talk about how they managed to complete the procedure and get a live and healthy cub at the exit (Fayomiet al., Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring).
A summary of the results of the work can be read in the press release of the National Institutes of Health Cryopreservation of immature testicular tissue leads to successful birth in monkeys - VM.
For the experiment, the scientists took five young male rhesus monkeys who had not reached puberty. For the first time, they were castrated by half, removing only one of the testes, which was immediately crushed and frozen. After 5-7 months, the second testis was removed, also crushed, but they did not freeze it to check the difference between cryopreserved and fresh tissue. Small pieces of seminal tissue of both types were implanted back into the macaques' scrotum and under the skin.
A few months later, puberty began in males: implants increased in size, and testosterone levels rose in the blood. Subsequently, in four out of five macaques, it remained constant – a sign that the seminal tissue copes with its glandular function (testosterone secretion). 8-12 months after implantation, pieces of seminal tissue were removed back from the monkeys' organisms to be thoroughly analyzed. In all cases, full-fledged seminal tubules formed in the tissue, which began to produce spermatozoa. Implants from fresh tissue grew slightly larger than from frozen, but not in all cases the difference was significant.
Finally, scientists decided to use one of the sections of the seed tissue for fertilization. It was crushed, spermatozoa were taken out and 138 eggs were fertilized with their help, of which 16 reached the stage of a full-fledged embryo. 11 of them were planted with female macaques, one of which became pregnant. A cub named Grady was born healthy. Now he is a little over 11 months old and he feels great.
Grady at the age of 12 weeks. Photo: Oregon Health and Science University.
The authors of the study separately stipulate that their experiment does not fully reproduce the situation with people. Firstly, they castrated the monkeys, which most likely will not happen with cancer patients. Secondly, the testicular tissue may contain individual tumor cells, especially in the case of blood cancer or the testicles themselves.
Nevertheless, the method may work for patients suffering from other types of cancer that does not penetrate the testes, or who have undergone radiation and red bone marrow transplantation for other purposes (for example, different types of anemia). According to the authors of the work, more than 60% of patients whose tissue has already been frozen as part of the Fertility Preservation Program in Pittsburgh and who are waiting for the technology of testicular growth to be officially approved fit these criteria.
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