Researchers removed stem cells and cultured sperm in the laboratory in a breakthrough that could lead to new treatments and drugs for men currently unable to have children.
The development raises hopes that young boys undergoing chemotherapy for testicular cancer will still be able to father their own children when they grow up.
The sperm was produced in a test-tube from the cells taken from a newborn mouse testicles and then injected into eggs to produce to twelve healthy babies, four male and eight female, which were all fertile and able to reproduce themselves in adulthood.
Dr Takehiko Ogawa, an urologist at Yokohama City University in Japan, said the production of sperm in the testes is one of the most complex processes in the body.
It has never been reproduced in a test tube in mammals before.
They achieved the feat by providing most of the cellular components found in the testicles in a dish and watched as the stem cells grew into sperm cells.
They then used IVF (in vitro fertilisation) techniques to produce male and female offspring that were themselves fertile.
The researchers, whose findings are published in Nature, said: "The obtained sperm resulted in healthy and reproductively competent offspring."
The testes tissue was still worked after being frozen in liquid nitrogen and could still be used several weeks later – suggesting it may be possible in humans to produce their own biological offspring years later.
Dr Ogawa and colleagues said: "We have demonstrated that the organ culture conditions, without a circulatory systems in vivo (in the living body), can support the complete spermatogenesis (sperm production) of mice.
"Therefore, extending the present results to a wide range of species by refinements and the individualisation of culture conditions to each of them seems promising."
Professor Shahin Rafii, a geneticist, and Dr Marco Seandel, an oncologist, of Weill Medical College in New York, reviewed the study for the journal and said it offers hope for young boys with cancer who, unlike men, cannot freeze their sperm before treatment.
They said the blueprint for producing mature sperm in a laboratory dish has eluded reproductive biologists for decades and the researchers "meet this challenge in mice."
Prof Rafii and Dr Seandel said: "The preservation of fertility is a major concern for patients requiring therapy, such as chemotherapy or radiation therapy, that can inadvertently destroy germ cells.
"In men, this problem can be mitigated by banking sperm before treatment. The solution is less straightforward in prepubescent boys.
"In this scheme, boys would undergo testicular biopsy before chemotherapy or radiation therapy, to obtain tissue for cryopreservation (freezing).
"If infertility occurs, the testicular fragments could be thawed and sperm obtained from organ culture for IVF."
Dr Allan Pacey, an expert in infertility at the University of Sheffield, said it was "a small but important step".
"This is a very interesting study," he said.
"There have been several attempts to create or 'grow' animal sperm in the laboratory by various different approaches.
"However, none have been wholly successful and when the sperm have been used, the pups born have not been healthy and have soon died.
"This could help discover new drugs or treatments to stimulate infertile men to produce more or better sperm. It also may help preserve the fertility of some males.
"I think this study is a small but important step in understanding how sperm are formed which may, in time, lead to us being able to routinely grow human sperm in the laboratory."
They then used IVF (in vitro fertilisation) techniques to produce male and female offspring that were themselves fertile.
The researchers, whose findings are published in Nature, said: "The obtained sperm resulted in healthy and reproductively competent offspring."
The testes tissue was still worked after being frozen in liquid nitrogen and could still be used several weeks later – suggesting it may be possible in humans to produce their own biological offspring years later.
Dr Ogawa and colleagues said: "We have demonstrated that the organ culture conditions, without a circulatory systems in vivo (in the living body), can support the complete spermatogenesis (sperm production) of mice.
"Therefore, extending the present results to a wide range of species by refinements and the individualisation of culture conditions to each of them seems promising."
Professor Shahin Rafii, a geneticist, and Dr Marco Seandel, an oncologist, of Weill Medical College in New York, reviewed the study for the journal and said it offers hope for young boys with cancer who, unlike men, cannot freeze their sperm before treatment.
They said the blueprint for producing mature sperm in a laboratory dish has eluded reproductive biologists for decades and the researchers "meet this challenge in mice."
Prof Rafii and Dr Seandel said: "The preservation of fertility is a major concern for patients requiring therapy, such as chemotherapy or radiation therapy, that can inadvertently destroy germ cells.
"In men, this problem can be mitigated by banking sperm before treatment. The solution is less straightforward in prepubescent boys.
"In this scheme, boys would undergo testicular biopsy before chemotherapy or radiation therapy, to obtain tissue for cryopreservation (freezing).
"If infertility occurs, the testicular fragments could be thawed and sperm obtained from organ culture for IVF."
Dr Allan Pacey, an expert in infertility at the University of Sheffield, said it was "a small but important step".
"This is a very interesting study," he said.
"There have been several attempts to create or 'grow' animal sperm in the laboratory by various different approaches.
"However, none have been wholly successful and when the sperm have been used, the pups born have not been healthy and have soon died.
"This could help discover new drugs or treatments to stimulate infertile men to produce more or better sperm. It also may help preserve the fertility of some males.
"I think this study is a small but important step in understanding how sperm are formed which may, in time, lead to us being able to routinely grow human sperm in the laboratory."
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