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Sperm Tissue Freezing Seen as Major Advance


A new technique to freeze sperm-producing tissues can provide "biological immortality" for males, a finding that researchers believe may ultimately have a major impact on conserving endangered species, protecting valuable research animals and preserving the reproductive ability of males who undergo intensive chemotherapy for cancer.

The technique may even make it possible for men with abnormally low sperm production to reproduce.

Fertility specialists routinely freeze sperm itself, but the freezing process is tricky and unique for each species. In addition, frozen sperm has a relatively short lifetime and researchers are limited to the amount of sperm frozen.

Veterinarian Ralph L. Brinster, a pioneer in genetic engineering of animals, and his colleagues at the University of Pennsylvania report today in the journals Nature and Nature Medicine that spermatogonia--the tissues that produce sperm--can be easily frozen and stored for long periods.

When the tissue is thawed out, it can be transplanted into the original donor or a host, where it begins making unlimited quantities of fresh sperm. Although Brinster has not yet attempted to fertilize eggs with the sperm, he has every confidence that it can. "I would be very surprised, closer to amazed, if it didn't fertilize an egg," he said.

"This is a brilliant piece of work," said Dr. Geoffrey Sher of the Pacific Fertility Center in San Francisco.

"It's very important, not only for the freezing, but also for the fact that you can put cells from one species into another and get them to develop into reasonable looking sperm," said biologist George Seidel Jr. of Colorado State University.

Sperm are routinely frozen today for a variety of purposes, including breeding of cattle and artificial insemination of humans, but results can be varied. Bull sperm freezes easily. Human sperm, however, is variable in its ability to survive the process.

"Sperm from some men survives very well, while sperm from other men does not survive at all, for reasons we don't understand," Seidel said. "But for most species, it's difficult, for reasons we also don't understand."

Brinster has circumvented those problems by focusing on spermatogonia, the cells that serve as the source for all sperm. Spermatogonia are incredibly productive. "Every time a human male's heart beats, he produces 1,000 sperm, from puberty to old age," Brinster said. "And every one is different. That accounts for the diversity of the species.

"All nature cares about is that cell [the spermatogonia] and its progeny. It doesn't care what the body is like that carries it. When you capture the sperm cell, you capture the individual. That's a kind of immortality."

Spermatogonia from an endangered species, for example, captures the genetic identity of an individual male. The conserved tissue could expand the breeding population of a small group, limiting the risk to the species from inbreeding.

Sperm-producing cells also might be preserved from an exceptionally speedy racehorse or from an unusually fecund bull.

Surprisingly, he said, people have not really attempted to freeze these tissues before. But his team found that they could readily freeze and thaw the cells using standard techniques.

"I don't want to denigrate my own work, but this was incredibly easy," he said.

Once mouse cells were unfrozen, the team reports in Nature Medicine, they could be easily transplanted back into the original donor or into so-called nude mice. Because nude mice have no immune system, they do not reject such transplants. The cells were tagged by genetic engineering techniques so they and the sperm they produced could be readily distinguished from sperm produced by the recipient.

Brinster reported in Nature that they also froze rat spermatogonia, then transplanted the thawed tissue into nude mice, which began producing apparently healthy rat sperm.

"That's really fascinating," Brinster said. "How does a mouse . . . cell nourish a cell from an animal that . . . is so different in morphology [size and shape]?"

Brinster is working on achieving the same feat with larger animals. The team then will proceed to human tissues.

He also is attempting to grow spermatogonia in the laboratory so that a small number taken from a person or an animal can be converted into a much larger quantity. That will be important in cases where only a small number of spermatogonia can be obtained from a biopsy. Expanding numbers is also important in genetic engineering of animals, when only a few spermatogonia may bear a desired trait.

If Brinster's technique is eventually used in humans, the first applications most probably will involve men whose testes have been lost to cancer or injury or whose spermatogonia have been destroyed by chemotherapy. Tissue could be frozen before surgery or chemotherapy, then later reimplanted in the donor or a surrogate.

The surrogate could be another human or even, Brinster suggests, a mouse, although the specter of a mouse producing human sperm for human reproductive purposes triggers skepticism among some.

"It is a long leap of faith between what they have done in animals and potential applications in human conditions," Sher said.

Nonetheless, proponents say, the approach might be able to help men who do not produce a sufficient number of sperm to be fertile. Some men are infertile, Seidel said, because conditions in their testes are not right for spermatogonia to develop into sperm. "What Brinster has given us is an alternative right place and right time--in the testes of another animal in another species," he said.

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