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Scientists have discovered that some treatments for cancer and sickle cell disease can destroy the germ cells that develop into sperm in the testicles of young boys. In some pre-pubertal boys, the treatment of sickle cell disease causes the complete destruction of all their germ cells, called spermatogonia.
The study, published in Human Reproduction is the first to describe the effects of these treatments on the amount of spermatogonia, although boys who have undergone chemotherapy or radiotherapy are known to be at risk of reduced fertility in adulthood.
As a result of their findings, the researchers say that and freeze testicular tissue for the preservation of fertility, this should be done before boys undergo a type of chemotherapy that uses high doses of drugs called "alkylating agents" ". This would give boys the hope of restoring their fertility when they become adults. Before puberty, boys are generally unable to produce sperm samples that can be frozen and kept for a period when they might want to start a family. Transplantation of testicular tissue in patients after treatment is a possible way to restore fertility, but, at present, the means to generate sperm from immature testicular tissue preserved are experimental and it is not possible to restore fertility. There has been no pregnancy to date. It may also depend on sufficient quantities of healthy spermatogonia preserved successfully.
Under the direction of Dr. Jan-Bernd Stukenborg, Associate Professor at the Karolinska Institute and University Hospital (Stockholm, Sweden), a group of international researchers badyzed the testicular tissues collected. Fertility conservation between 2014 and 2017 of 32 boys, average age 6 years, living in Sweden, Finland and Iceland, exposed to high-risk infertility treatments: testicular irradiation, chemotherapy or radiotherapy in preparation for A bone marrow transplant because they had cancers or blood disorders such as sickle cell disease, thalbademia major or Fanconi anemia. Sickle cell disease is the main reason for bone marrow transplantation in children who do not have cancer. Twenty boys had the tissue removed after the initial chemotherapy and 12 had it taken before starting any treatment. In addition, they examined 14 samples of healthy testicular tissue stored in the biobank at Karolinska Hospital.
They counted the number of germ cells found in a section of small tubes in the testes where spermatogonia, called seminiferous tubules, is created. "We could compare the number of spermatogonials with those found in healthy boys as a way to estimate the effect of medical treatment or the disease itself on a patient's future fertility." ", says Dr. Stukenborg
. The number of germ cells present in the seminiferous tubule cross-sections was significantly depleted and close to zero in patients treated with alkylating agents. The germ cell pool in five sickle cell boys was completely depleted and very low in another; had been treated with nonalkylating agents or in the tissues of biobanks. "
Alkylating agents are used in some chemotherapies, destroying cancer cells by damaging their DNA." Hydroxyurea is a chemotherapy agent that is often used to treat the effects of blood disorders such as sickle cell disease, where It improves the function of red blood cells It reduces the symptoms of sickle cell disease but does not cure Bone marrow transplants offer the best chance of healing or remission in the long term However, before a transplant, the patient's own bone marrow must be destroyed and the immune system removed by radiotherapy or chemotherapy so that the body does not reject the transplant of another person.
Co-author, Dr. Cecilia Petersen, senior "Our results" a dramatic decrease in the number of germ cells in boys treated with alkylating agents and in patients with sickle cell disease treated with Hydroxyurea suggests that storage of frozen testicular tissue from these boys should be done before these treatments are initiated, they must be communicated to physicians, as well as to patients and their parents or caregivers. "However, until the sperm capable of fertilizing eggs is produced from stored testicular tissues, we can not confirm that the amount of cells could determine the success of tissue transplantation at the same time. adulthood.Other research on this topic is needed to establish a realistic technique for preserving fertility. "
The authors point out that for some boys, the disease itself may have already affected the number of spermatogonia even before the start of treatment. The co-author, Professor Kirsi Jahnukainen, Senior Consultant in Pediatric Oncology at the Pediatric Hospital of the University of Helsinki, Helsinki (Finland), said: "Among the patients who had not previously treated with chemotherapy, there were several boys with low numbers of germ cells for their age.This suggests that some non-malignant diseases that require a bone marrow transplant can affect the fertility of young boys even before they get older. Exposure to a treatment that is toxic to the testes. "
Researchers say that it is possible for germ cells to recover post-treatment levels highly toxic to the testes, but that high doses of the testicles are noticeable. alkylating agents and testicular radiotherapy, including total body irradiation, are strongly badociated with permanent or long-term infertility.
Prof Jahnukainen adds: A group of boys who have received bone marrow transplants are now in their thirties. Recent data suggests that they may have a great chance of recovering their sperm production, even though they have received high dose alkylation therapies, as long as they do not have a chance to recover their semen production. had no testicular irradiation. "
A limitation of the study was that the biobank did not have detailed information on previous medical treatments and testicular volumes in these patients.
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