Source: Wired
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Women May Replenish Eggs
Mar. 10, 2004 By Kristen Philipkoski
The long-held belief that women are born with their lifetime
supply of egg cells is now in doubt, and the change could
revolutionize fertility treatments.
The findings of a new study raise the possibility that
women, like men, replenish their reproductive cells
throughout life. The research, published in the March 11
issue of Nature, was done in mice, a mammal often used as a
model for human biology. If the results can be replicated in
humans, the findings will upend a doctrine held by fertility
researchers for half a century.
The knowledge could lead to a flood of new ways to approach
infertility associated with cancer treatments like
chemotherapy and radiation, as well as diminishing fertility
in older women.
"If these cells do in fact exist in humans and female eggs
regenerate throughout adult life, essentially all beliefs of
the development and aging of the ovaries will have to be
revised and reanalyzed," said Jonathan Tilly, the study's
lead author and reproduction expert at the Vincent Center
for Reproductive Biology at Massachusetts General Hospital.
The study found that female mice have "germ stem cells." In
females, these cells generate new egg cells throughout the
life of the mouse; in males, they generate new sperm. All
male mammals are known to have these cells, but a long-held
dogma said that females did not. That's why, experts
believed, women's eggs became old and unable to form embryos
later in life.
But Tilly's research found that female mice do have germ
stem cells that elicit the growth of new eggs, and he
believes the same will likely be true in humans. If so,
these germ stem cells, instead of ovaries and eggs, will be
a new focus for infertility researchers.
"If in fact we could tap the follicle reserve as a means to
postpone ovarian failure, that could be the most
significant advance in reproductive medicine since the
advent of in-vitro fertilization more than 25 years ago,"
said Marian Damewood, president of the American Society of
Reproductive Medicine.
Germ stem cells could potentially be isolated and frozen for
use later in life for women who face chemotherapy or
radiation treatments, as well as aging women who want to
delay childbirth.
The cells could also lead to a revolutionary treatment for
menopause, Tilly said. For years, doctors have recommended
hormone replacement therapy for the symptoms of menopause,
like hot flashes, sleep disturbance and mood swings. But
hormone replacement contains just two hormones, estrogen
and progestin, while the ovaries (which cause menopause
when they stop releasing eggs) produce many more hormones.
Germ stem cells would produce the complement of female
hormones associated with reproduction, and could be a more
effective therapy.
Researchers haven't yet perfected a way to preserve germ
stem cells, but they have made headway in techniques to
freeze male cells, which would likely translate directly to
female cells.
To prove that women do indeed have germ stem cells, Tilly
and his colleagues are trying to isolate the cells in mice,
then find their unique genetic signals. If they can find the
same signals in human cells, that will be proof that women
also have germ stem cells.
The belief that women are born with the number of eggs
they'll have for the rest of their lives was first posited
in 1921. The declaration was solidified with a landmark
study in 1951, and it has been a core dogma about female
fertility ever since. The new research will surely send
many fertility researchers back to their files in hopes of
deciphering studies that had previously puzzled them,
Tully said.
It will also lead to a spike in new work, said Dr. Allan
Spradlin, a fertility researcher at the Howard Hughes
Medical Institute and Carnegie Institution in Baltimore,
Maryland, who wrote a review of Tilly's work, also published
in Nature.
"Now that germline stem cells in the mouse have been
discovered, Spradlin wrote, "determining the cellular and
molecular mechanism that maintain them as such will be the
mission of many a scientist."