March 12, 2004

MGH study finds female mammals produce egg cells into adulthood

An underlying principle of female reproductive biology appears to have been overturned by a report from MGH researchers. In the March 11 issue of Nature, the investigators report that female mice can make new egg cells well into adulthood. It has been believed that most female mammals are born with a finite supply of these cells, called oocytes, that are lost at a steady rate until the supply is exhausted, leading to menopause in women.

"If these findings hold up in humans, all theories about the aging of the female reproductive system will have to be revisited," says Jonathan Tilly, PhD, (left), of the Vincent Center for Reproductive Biology at the MGH, the paper's lead author. "Eventually this could lead to totally new approaches to combating infertility."

For several years Tilly's group has been studying the mechanisms behind the death of oocytes and follicles, the tiny sacs in which the eggs grow. The vast majority of oocytes die through a process called programmed cell death or apoptosis. The team's earlier research confirmed that oocytes destroyed by cancer treatment die through apoptosis. To provide context to their efforts to inhibit oocyte death, the researchers measured the numbers of healthy and dying follicles in mouse ovaries through the animals' lifespan.

What they found was remarkable. In young adult animals, the researchers measured 1,200 dying follicles per ovary, compared with about 3,000 healthy follicles remaining, levels that continued well into maturity. Although such a high rate of follicle loss would completely deplete a fixed population of oocytes, female mice retain healthy egg cells well past one year of age.

"Finding such high follicle degeneration without a reduction in the number of healthy follicles brought us up against the dogma of a fixed supply of oocytes," Tilly says. "The only probable interpretation was that the ovary had to be retaining the ability to make new oocytes and follicles." To investigate that possibility, the researchers ran additional experiments, all of which confirmed that new egg cells were being generated and suggested that the kind of stem cells that make sperm in males also are active in adult females.

"These are basic biological findings that may change everything in our field," Tilly says. "Although there's no way to say how long it may take for these findings to actually affect the care of patients, we're very excited about the new set of scientific questions we have to investigate." Co-authors of the study are first authors Joshua Johnson, PhD, and Jacqueline Canning, along with Tomoko Kaneko, MD, PhD, and James Pru, PhD, all of the Vincent Center for Reproductive Biology.