A baffling inconsistency in a Boston lab is threatening to overturn a dogma of reproductive biology: that female mammals produce no new eggs after birth. A series of studies on mice has prompted a flabbergasted team of biologists to conclude that mouse ovaries harbor a previously undiscovered type of stem cell that can form new eggs through adulthood. The finding touches on everything from fertility and aging to the childbearing capacities of young cancer patients.
The discovery came about by chance. Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital in Boston, and his colleagues were studying ovarian failure, which is frequently caused by chemotherapy and radiation treatments. In the course of an experiment, the researchers harvested ovaries from mice at different stages of life and counted the healthy follicles, each of which holds a single oocyte, or egg cell. Then they counted the number of dying egg cells in the same animals. The scientists were surprised to find that up to 1200 oocytes were dying at any given time as the animals approached adulthood. Mice are born with roughly 5000 oocytes, so this rate should have wiped out their egg supply in a matter of weeks.
Examining the ovaries, the researchers noticed roughly 65 cells in each that resembled fetal germ cells--the cells in a fetus that transform into either eggs or cells that produce sperm. To see whether the germ cells were producing oocytes, Tilly's team collected mice with cells engineered to express a green fluorescent protein. Then they grafted half of an ovary from a regular mouse onto the engineered animals' ovaries. After several weeks, green oocytes were visible in the transplanted ovarian tissue. The germ cells from one side of the ovary had migrated to the other, it appeared, and formed new egg cells, the team reports in the 11 March issue of Nature.
"This is almost like finding out that the world is actually flat," says Kutluk Oktay, an infertility specialist at Cornell University's Weill Medical College in New York City. The work "challenges an entirely established concept, in a very elegant way." The Tilly lab's findings could shed light on why some cancer survivors emerge from treatment infertile but others don't. And if researchers can find ways to preserve some germ stem cells, or identify drugs that don't target them, Tilly suggests, fertility could be protected--even if existing oocytes are killed by treatment.