Recalibrating the Biological Clock?

13 April 2009 (All day)

Kang Zou et al., Nature Cell Biology Advance Online Publication (12 April 2009)

Miraculous birth. A Chinese group isolated stem cells from mouse ovaries, transplanted them into sterilized mice, and got these normal babies.

A new study challenges the long-held belief that female mammals start life with a limited number of eggs and cannot produce new ones after birth. For the first time, a Chinese group has found mouse cells that produce new eggs when transplanted into sterilized mice and give rise to normal offspring. The findings are already inflaming the debate over when and how female mammals generate eggs; if confirmed, they could offer hope of new options to treat human infertility.

For at least 50 years, the theory that female mammals do not produce new eggs, or oocytes, after birth seemed to explain reproductive features such as menopause, which presumably occurs when the store of eggs is depleted. But in 2004, reproductive biologist Jonathan Tilly and colleagues at Harvard Medical School in Boston challenged this dogma by reporting that oocytes in mouse ovaries die too quickly for a limited supply to last a reproductive life span. And after the researchers grafted pieces of normal ovaries into mice engineered to express green fluorescent protein (GFP), they observed green oocytes in the transplanted tissue. These oocytes were presumably generated by an egg-producing line of cells known as female germline stem cells (FGSCs) that migrated into the graft. But no one had succeeded in culturing these cells.

Reproductive biologist Ji Wu and colleagues at Shanghai Jiao Tong University in China tried an overlooked technique called immunomagnetic isolation, in which tiny magnetic beads coated with an antibody latch onto a protein expressed only by germline stem cells. A magnetic screen collects cells with attached beads. Wu's group was able to isolate FGSCs from newborn and adult mice and culture them through numerous cycles of division, even freezing and thawing them without any apparent ill effects. They then infected the cells with a harmless virus carrying the GFP gene and transplanted them into the ovaries of sterilized mice. After mating with normal males, the females gave birth to healthy, fertile offspring that carried GFP, the group reports online this week in Nature Cell Biology.

"It's a beautiful paper," says Evelyn Telfer, a reproductive biologist at the University of Edinburgh in the U.K. "By producing live young, these cells have passed the ultimate test to prove their germline credentials," says Telfer. But not everyone is convinced. "On the face of it, this is indeed dramatic and significant, but large claims require searing critical scrutiny, and I will reserve final judgment until it is replicated elsewhere," says Roger Gosden, a reproductive biologist at Weill Cornell Medical School in New York City. Tilly predicts confirmation won't be long in coming. Wu and her colleagues "spell out a simple protocol [for isolating FGSCs] that any lab can now try," he says.

If FGSCs can be found in human ovaries, they could be exploited to treat infertility due to cancer treatments, disease, or aging, says Kutluk Oktay, a reproductive endocrinologist at New York Medical College in Valhalla. "I have not been excited about a scientific piece like this for a long time," he says.

Posted In: