Germ cell transfer boosts fertility.

Deep within a man's testes, primitive germ cells undergo continuous replication. Remarkably, germ cells that mature into sperm represent the only self-renewing cells in the adult body that can pass genetic information to the next generation. Thus they are, in a sense, immortal.

In contrast, the germ cells that mature to form eggs are present at birth. The female reproductive tract cannot replenish that supply.

Researchers from the University of Pennsylvania's School of Veterinary Medicine in Philadelphia now report transferring germ cells taken from virile male mice to the testes of infertile mice. Those cells matured to form sperm, and in some cases the recipients went on to father offspring.

"This opens up the field of male germ cell experimentation in a manner that wasn't possible before," says lead author Ralph L. Brinster. The researchers describe their findings in two papers published in the Nov. 22 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

In the first report, Brinster and James W. Zimmermann took germ cells, including so-called stem cells, from fertile male mice. Next, they injected those cells directly into the seminiferous tubules -- the sperm-producing tubes of the testes -- of mice producing few or no sperm.

The researchers discovered that the donated cells set up shop in the recipients' tubules. Once there, the stem cells behaved normally: Some replicated to form additional stem cells, while others ripened into cells that would eventually become sperm. Brinster and Zimmermann showed that about one-third of recipient testes produced sperm.

"This is a powerful group of cells that has a lot of potential use in biology and medicine," Brinster says.

In the second paper, Brinster and Mary R. Avarbock transplanted stem cells taken from fertile mice to the testes of mice with low or no sperm count. This time, the researchers showed, the procedure yielded mature sperm cells in more than 70 percent of the recipients.

A question remained: Could the recipient males sire a litter of pups?

To find out, the researchers mated two low-sperm-count mice with female mice. In the most successful case, 80 percent of the resulting pups came from donorderived sperm and thus carried the donor dad's DNA.

"This is an exciting piece of work," comments Peter Donovan of ABL-Basic Research Program, a part of the National Cancer Institute located in Frederick, Md. Donovan points out that such research could lead to a treatment for infertility in men. Researchers might someday take germ cells from a man with a low sperm count, culture them in the laboratory, and use them to replenish the man's testes, he says.

Such research could also pave the way for germline gene therapy, the technique of replacing a disease-causing gene with a healthy gene in a cell that affects succeeding generations.

Theoretically, researchers could obtain germ cells from a man who carried a genetic flaw, explains Martin Dym, a cell biologist at the Georgetown University Medical Center in Washington, D.C. They could snip out the mutant gene and replace it with a normal one. The researchers would then transfer the corrected germ cells to the man's testes. Any offspring derived from those engineered cells would not carry the genetic flaw, he adds.

Scientists are already experimenting with somatic gene therapy, in which a desired gene is inserted in the DNA of a body cell that dies after a short period. With germline gene therapy, researchers would insert genes that get passed down to future generations.

Right now, such gene insertions remain risky. "It's premature to think about [germline gene therapy] in humans," Dym says. Yet, he adds, if scientists can iron out the glitches, such an approach would offer tremendous benefits. "Conceivably, you could use the technique to eradicate genetic diseases."