First mammal born from lab-grown cell.

A pudgy, 7-month-old mouse scurrying around a cage at the Jackson Laboratory in Bar Harbor, Maine, represents the latest thought-provoking experiment in the reproductive sciences. The implications of this unique animal range from the recovery of endangered species to the protection of a cancer patient's reproductive capability.

Two Jackson investigators, John J. Eppig and Marilyn J. O'Brien, created the rodent from an immature egg cell harvested from the ovary of a newborn mouse. By growing this so-called primordial oocyte to maturity outside the mouse's body, the scientists have taken a significant step beyond traditional in vitro fertilization (IVF), the test-tube technique in which investigators fertilize an already mature egg with sperm.

"It's a real important feat. On the other hand, it's a long way from practical use. It's a much more difficult problem in species other than rodents," says George E. Seidel Jr. of the Animal Reproduction Laboratory at Colorado State University in Fort Collins.

For their experiments, Eppig and O'Brien first removed the ovaries from a newborn mouse and grew the organs in laboratory dishes. At the end of a week, they used enzymes to digest everything but the ovary's primordial follicles, balls of support cells with an oocyte at the center.

Though the follicles hold many thousands of primordial oocytes, only a few hundred will ever produce a mature egg. To draw on that untapped resource, the investigators placed the primordial follicles in a broth of carefully selected hormones and nutrients that triggered further oocyte development. After about 2 weeks, slightly more than 30 percent of the oocytes had matured into eggs ready for insemination.

If a successfully fertilized egg cell then completed its first cell division, a relatively rare event, the researchers inserted the resulting two-cell embryo into the oviduct of a female mouse. Of 190 embryo implantations, only two mice gave birth, Eppig and O'Brien report in the January Biology of Reproduction. One pup is thriving, but the other was stillborn or died within hours of birth.

As an immediate consequence of their work, Eppig and O'Brien suggest that lab-grown primordial oocytes offer a novel opportunity to study how oocytes develop into mature eggs, to test compounds that may cause birth defects or infertility by damaging oocytes, and to develop new contraceptives.

On a more speculative level, says Eppig, the ability to artificially mature other species' primordial oocytes could provide agricultural breeders and those seeking to protect endangered species with a valuable new way of quickly generating progeny from a specific animal. "You could produce a herd [from a fetus] before that fetus would ever be old enough to give birth," says Eppig.

Eppig has also had discussions with conservation biologists about whether they could increase the dwindling Florida panther population by using the primordial oocytes of the cats to impregnate closely related panther species.

Further down the road, says Eppig, girls and young women who face potentially sterilizing cancer therapies might freeze primordial oocytes that could later be matured to permit pregnancy through IVF. Lab-grown oocytes might also alleviate the severe shortage of donor eggs for infertile couples, he adds.