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Ova Discovery Is One for the Biology Texts

Mice study disproves dogma that females are born with a finite number of eggs.

March 11, 2004|Rosie Mestel | Times Staff Writer

The long-held biological dogma that females are born with all the eggs they will ever have is wrong, according to a study published today in the journal Nature. Instead -- at least in mice -- eggs are renewed throughout life, probably from a store of stem cells in the ovaries.

If the finding holds true for humans too, researchers envision a range of possible applications -- including better, fertility-sparing therapies for cancer patients, prolonged fertility and improved health for women after menopause.

"I think that all of reproductive biology would have to be reevaluated in the light of this," said Frank Bellino, a deputy associate director at the National Institute on Aging.

Every biology student learns that while men can produce fresh sperm into their dotage, women are born with a fixed supply of 1 million to 2 million developing eggs that slowly die off as they age -- leading to menopause and infertility.

That conclusion was reached through simple observation of ovarian tissues long before sophisticated techniques of molecular biology were developed and was never questioned before.

"It's in every textbook that you pick up -- it's probably one of the most basic doctrines of our field," said Jonathan L. Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital and principal author of the Nature study. The belief dates at least to the early 20th century and had been set solidly in stone by 1951, he said.

Tilly's team first suspected that the dogma might be false after discovering that eggs in mouse ovaries died at such a rapid clip that their ovaries would be stripped of eggs in a mere two weeks unless the supply were somehow replenished.

Yet mouse ovaries remain well-stocked with eggs for a year of the animal's lifespan.

"We just couldn't reconcile the fact that there was so much death going on, yet the ovaries continued to function," Tilly said.

In subsequent experiments, the scientists found clear signs that eggs were being renewed. For instance, they found that cells in the ovaries were dividing, which would be needed to make fresh eggs. They also detected a special type of division known as meiosis that was specifically required for the final steps in the formation of eggs and sperm.

The scientists also treated mice with a drug, busulphan, that is known to block production of sperm in human testes. The ovaries of treated animals ran out of eggs within three weeks.

This finding implies that eggs are being renewed in ovaries in much the same way that sperm is renewed in testes.

Experts in reproductive medicine said the results, if confirmed in humans, might one day be used to extend fertility.

"That could be the most significant advance in reproductive medicine since the advent of in-vitro fertilization more than 25 years ago," said Dr. Marian Damewood, president of the American Society for Reproductive Medicine, in a statement.

Tilly said that if ovarian stem cells were frozen when a woman was young, years later they could be re-implanted into her ovaries and render her fertile after toxic, ovary-damaging chemotherapy treatments. They might also be returned to a woman to postpone menopause, he said.

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