It was known till now that women were born with all the eggs they'll ever have. But now Harvard scientists have found that ovaries of young women harbor very rare stem cells capable of producing new eggs. The researchers feel that harnessing those stem cells might one day lead to better treatments for women left infertile because of disease or age.
“Our current views of ovarian aging are incomplete. There's much more to the story than simply the trickling away of a fixed pool of eggs,” said lead researcher Jonathan Tilly of Harvard's Massachusetts General Hospital. Tilly has previous work in this direction which was much criticized by many experts. Even this new research needs to be replicated before being accepted.
A key next step would be to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University's Feinberg School of Medicine. The major point was how the researchers could be sure that the cells they thought were stem cells and not very immature eggs.
“This is going to spark renewed interest, and more than anything else it's giving us some new directions to work in,” said David Albertini, director of the University of Kansas' Center for Reproductive Sciences. While he has plenty of questions about the latest work, “I'm less skeptical,” he said.
Tilly, Mass General's reproductive biology director, first challenged that idea that women were born with all the eggs at birth in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.
This new report was published Sunday in journal Nature Medicine. He found healthy human ovaries to study. He collaborated with scientists at Japan's Saitama Medical University, who were freezing ovaries donated for research by healthy women in their 20’s who underwent a sex-change operation.
To differentiate between very immature eggs and stem cells the team latched onto a protein, DDX4, believed to sit on the surface of only those purported stem cells and fished them out. Then they inserted a gene that makes some jellyfish glow green into those cells. If the cells made eggs, those would glow, too. “Bang, it worked — cells popped right out” of the human tissue, Tilly said. Researchers watched through a microscope as new eggs grew in a lab dish.
Then they injected the stem cells into pieces of human ovary. They transplanted the human tissue under the skin of mice, to provide it a nourishing blood supply. Within two weeks, they reported tell tale green-tinged egg cells forming.
Dr Tilly said, “The primary objective of the current study was to prove that oocyte-producing stem cells do in fact exist in the ovaries of women during reproductive life, which we feel this study demonstrates very clearly. The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure.”
He told Nature, “These cells, when maintained outside of the body, are more than happy to make cells on their own and if we can guide that process I think it opens up the chance that sometime in the future we might get to the point of having an unlimited source of human eggs.”
That's still a long way from showing they'll mature into usable, quality eggs, Albertini said. And more work is needed to tell exactly what these cells are, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Tilly's work with great interest.
Orwig’s question was if these are useful eggs then why would women undergo menopause. Tilly argues that using stem cells to grow eggs in lab dishes might one day help preserve cancer patients' fertility. Further down the road, he wonders if it also might be possible to recharge an aging woman's ovaries.
Stuart Lavery, a consultant gynaecologist and director of IVF at Hammersmith Hospital, said the findings were “extremely significant” and “a potentially landmark piece of research”. He told the BBC, “If this research is confirmed it may overturn one of the great asymmetries of reproductive biology - that a woman's reproductive pool of gametes may be renewable, just like a man's.” While cautioning that the cells were “some way” from any clinical use, Lavery said they had potential, “particularly in young women facing sterilizing treatment such as chemotherapy”.
Dr Allan Pacey, a fertility expert at the University of Sheffield, said, “This is a nice study which shows quite convincingly that women's ovaries contain stem cells that can divide and make eggs. Not only does this re-write the rule book, it opens up a number of exciting possibilities for preserving the fertility of women undergoing treatment for cancer, or just maybe for women who are suffering infertility by extracting these cells and making her new eggs in the lab.”
The new research was funded largely by the National Institutes of Health. Tilly co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.
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