August 15, 2002 BOSTON (The Boston Globe) -- A laboratory in Pennsylvania has created mice that produce the sperm of goats and pigs, a technique with potential applications that range from helping human fertility to saving endangered species.
In the past, researchers have been able to use mice to grow the sperm of closely related species. The new work shows the same can be done with wildly disparate species, raising the prospect that human sperm could someday be grown in mice.
A team at the University of Pennsylvania School of Veterinary Medicine took a small piece of testicular tissue from a donor animal and inserted it under the skin on the back of a mouse with a compromised immune system. The tissue grew and, while still in the back, produced viable sperm from the donor.
It is, scientists say, an impressive technical feat, because the specialized tissues that produce sperm are very sensitive to variations in temperature or oxygen levels and are notoriously difficult to manipulate in the lab.
"The results are quite surprising," said Roger Gosden, who has followed the team's work and is the scientific director of the Jones Institute for Reproductive Medicine in Virginia. "Testicular tissue is pretty delicate."
The results, published in Wednesday's issue of the journal Nature, add to the dizzying technical progress now being made in reproductive biology, with scientists able to manipulate cells and tissues in ways that would have stunned a biologist working just a decade ago. The progress is driven by a rapidly growing market in reproductive technologies for farm animals and in human medicine, as well as simple scientific curiosity about how the very first steps of life unfold.
The cross-species work announced Wednesday is also remarkable because it deals with donors that have not reached sexual maturity.
If successful with humans, it could be used, for example, to help children with leukemia, said Ina Dobrinski, who was part of the team and is an assistant professor of large animal reproduction at the veterinary school.
The chemotherapy used to fight cancer also can leave patients sterile. With older patients, doctors can collect semen before the chemotherapy and freeze it for later use. But younger patients cannot produce viable sperm for donation, meaning they will never be able to conceive children.
With the new technique, a small amount of tissue could in theory be gathered before chemotherapy and then the resulting sperm could be saved.
That also would be an advantage in trying to save endangered species, according to Betsy Dresser, executive vice president for research at the Audubon Nature Institute in Louisiana. As the number of animals in a species falls, the diversity of the gene pool falls as well, threatening the health of the next generation.
Using the transplant, the genetic heritage of any male could be saved and passed on, even if the animal died young. The method, Dresser cautioned, has not been proven in other animals.
"Just because it works in pigs and goats does not mean it will work in other mammals," Dresser said. But "it is an exciting prospect that you might be able to save endangered species this way."
In one set of experiments, the team began with a small amount of tissue taken from the testicle of a newborn pig. The tissue was placed under the skin of a "nude mouse," a wrinkled, hairless mouse whose immune system has been weakened so it does not fight off foreign tissue. The mice were also castrated, so they would not produce hormones that might interfere with development of the grafted tissue.
The mouse then served as a host while the tissue grew from about 1 millimeter at the time of transplantation to between 4 and 8 millimeters after 10 weeks, according to the Nature paper. The grafts contained sperm, and the sperm moved actively and passed a number of other tests showing it was viable.
The researchers plan to try the same experiment using tissue from a primate, Dobrinski said. Gosden said he had tried a similar approach with human donors, but had been unable to get it to work well.
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