The long-held dogma about a woman's reproductive capabilities is that she is born with all her egg cells, and that they are finite. However a newly discovered type of stem cell in the ovary could mean big things for women’s health, possibly leading to new fertility treatments and maybe even a way to delay menopause.
Since the 1950s it has been thought that women are born with all of the egg cells they will ever have. But with the discovery of egg-producing stem cells in mice and humans, it now appears that the ovary can replenish its egg supply. Researchers led by Jonathan Tilly, a reproductive biologist at Massachusetts General Hospital in Boston, report the finding online February 26 in Nature Medicine.
The paper, entitled “Purification, propagation and characterization of mitotically active germ cells from ovaries of reproductive age women”, is available in the Advanced Online Publication of Nature Medicine at http://www.nature.com/nm/index.html and will be published in the March issue of the journal. It is also available at Oxford Journals.
The abstract of the article reads:For decades it was believed that a non-renewable pool of oocyte-containing follicles is established in female mammals at birth. This cornerstone of reproductive biology was challenged 5 years ago by a study reporting on the presence of mitotically-active germ cells in juvenile and adult mouse ovaries. Additional findings presented in this study and others that followed further suggested that mammals retain the capacity to generate oocytes during adulthood; however, isolation of oocyte-producing germline stem cells (GSC) as unequivocal proof of their existence remained elusive. This piece of information now appears to have been provided by Ji Wu and colleagues. In addition to showing that proliferative germ cells resembling male spermatogonial stem cells can be purified from neonatal or adult mouse ovaries and maintained in vitro for months, transplantation studies demonstrated that these cells generate oocytes in ovaries of chemotherapy-sterilized recipients that fertilize and produce viable offspring. Although these findings do not establish that oogenesis occurs in adult females under physiological conditions, they strongly support the existence of GSC in adult mouse ovaries. If equivalent cells can be found in human ovaries, stem cell-based rejuvenation of the oocyte reserve in ovaries on the verge of failure may one day be realized.
Other researchers hail the discovery as a genuine breakthrough with huge implications. “This is like discovering a new planet in our solar system that has a bacterium on it,” says Kutluk Oktay, a reproductive biologist at the New York Medical College in Valhalla. At the very least, he says, the cells offer hope for extending a woman’s reproductive life span.
Tilly didn’t set out to overturn the accepted dogma that women don’t make new eggs. As part of their research into the onset of menopause, he and his colleagues developed ways to track the death of egg cells over time. When the researchers counted the number of healthy egg cells in mouse ovaries, they saw a steady decline with age as expected. But the team also found that dying cells greatly outnumber the starting population of eggs. “What we had was a math problem,” Tilly says. “We refocused all of our efforts on this glaring mathematical dilemma.”
In 2004, Tilly’s group reported the answer to their math problem: There are more dying eggs than healthy ones because stem cells in mouse ovaries are constantly making more eggs, which then die off. The discovery didn’t go over well. “The vast majority of our colleagues were not very receptive,” Tilly says. Many of those who did accept the existence of egg-forming stem cells in mice didn’t think humans would have similar cells.
Tilly and his colleagues isolated stem cells from ovaries that had been removed from six women during sex reassignment surgeries at Saitama Medical Center in Japan. Only about 1.5 percent of cells in the ovaries fit the stem cell profile. The researchers compiled molecular profiles of the cells and demonstrated that the stem cells are able to make precursors to eggs when transplanted into other ovaries.
Tilly’s group convincingly demonstrates that stem cells in human ovaries can make egg cell precursors. But it remains to be seen if the cells can make mature gametes, says Evelyn Telfer, a reproductive biologist at the University of Edinburgh.
Stopping the depletion of eggs or keeping ovaries functioning could help stave off many of the health problems women experience after menopause, Tilly says. “If we can somehow control this biological clock, to me, the possibilities are endless.”
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