Friday 8 May 2009

Stem Cells May Restore Female Fertility


Rather than sticking to a schedule set by social convention, more and more women are opting to wait until their late 30s and early 40s to have children. In 2005, ten times as many women had their first child between the ages of 35 and 39 as in 1975, and thirteen times as many had their first between 40 and 44. There are apparent advantages of waiting to start a family, including having achieved many personal and career goals and being more financially stable. In contrast, there is also a big downside: the longer you wait, the harder it is to get pregnant. The reason is straightforward—a woman is born with all the eggs, known as oocytes, she’ll ever have and over time the supply is depleted. But researchers in China say it may one day be possible for women to rewind their biological clocks by repopulating their ovaries with new eggs using stem cells.

In a study that has been deemed “quite dramatic,” researchers led by Kang Zou and Ji Wu from the School of Life Science and Biotechnology at Shanghai Jiao Tong University harvested cells they call female germline stem cells (FGSC) from the ovaries of five-day-old and adult mice. The cells were cultured for more than six months and modified to produce a green fluorescent protein so they could be easily tracked. Then the scientists used the FGSC’s to reseed the ovaries of mice whose eggs had been killed off. The sterilized mice produced new eggs, and after natural mating, 80 percent went on to produce healthy offspring that were themselves fertile. The green protein was present in many of the babies, which suggests they came from eggs grown from the stem cells. “These results suggest that oocytes can be regenerated in sterile recipient females by transplantation of FGSCs,” the study authors wrote.

This is the first time scientists have obtained cells from an adult mammal that appear capable of producing new eggs and healthy offspring. “If you are looking to disprove that females cannot make new eggs, this paper proves it. It’s a really significant paper,” said Jonathan L. Tilly, a professor of obstetrics, gynecology and reproductive biology at Harvard Medical School. “This is the smoking gun.”

If the findings are confirmed, they could offer a host of new options for infertile women. For example, those who wish to delay childbearing or who are facing sterilization as a result of cancer treatment might be able to stockpile their egg stem cells for use later in life. Or if women who are infertile because of their age still harbor the cells, scientists may be able to find a way to stimulate them into producing new eggs, some experts say. “We have lot of patients who cannot get pregnant because they have run out of eggs or their eggs are of poor quality because of their age. The only option they have is adoption, which is not so easy, or egg donation, which means the child would not be their genetic child,” said Roger G. Gosden, director of reproductive medicine at Cornell Weill Medical Center in New York, who was not involved in the research. “The research means egg donation from a fertile woman might not be necessary because she could have her own genetic child engineered from her stem cells.”

The findings could also benefit stem cell research by providing a new source of eggs, which are crucial for producing stem cell lines tailored to individual patients and diseases but are difficult to obtain and controversial.

However, some experts remain cautious, saying the work needs to be replicated more carefully in mice and in other species. “The aging process of the human egg differs fundamentally from that of the mouse egg,” said David L. Keefe, a professor of obstetrics and gynecology at the University of South Florida. “Except at Disney World, humans are not large mice.”

“This is another chapter in what has been a very controversial story, where some scientists have gone against the dogma which states that in mammals, such as mice and humans, all the progenitor germ cells that could give rise to eggs have already done so by birth,” said Professor Robin Lovell-Badge, a researcher into stem cells at the MRC National Institute for Medical Research in London. “This paper will stimulate lots of activity in the scientific community, as happens when any dogma is challenged. This is a good thing. But what would be unfortunate is if this paper is hyped as a cure for female infertility. A lot more work is needed to understand what these new cells really are, and to verify the findings and the claims.”

The study was published online by the journal Nature Cell Biology

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