Are women born with all the eggs they will ever have, or do they possess
the ability to make more?
That debate is in full force this
week as researchers led by Kui Liu at
the University of Gothenburg in Sweden say they have ruled out the tantalising
possibility that ovarian stem cells exist.
Back in February, Jonathan
Tilly and his colleagues at Massachusetts General Hospital in Boston
claimed that they had found stem
cells in human ovaries. The news was incredible – the cells were able to form
new immature eggs, and it was hoped that they could be harnessed to improve in
vitro fertilisation and help older women to conceive a healthy baby.
But it hasn't been easy to
overturn the dogma that women are born with all the eggs that they will ever
have.
Brand new eggs
The human ovary contains up to
2 million immature eggs, and every month one of these matures and is
released. It has been long-held that mammals are born with their lifetime's
supply of eggs. That was until Tilly and various other groups discovered what
they believed to be stem cells in mouse ovaries. The groups said that these
cells were able to divide into new egg cells.
As these ovarian stem cells
mature, a protein called vasa gets pulled from the surface of the cell into the
centre, says Tilly. So his team looked for cells with vasa still on their
surface in human ovarian tissue.
They found a small number and
identified them as stem cells because when they were removed from the tissue
and placed inside a mouse, they divided into new cells capable of forming
early-stage eggs.
Liu's team used a different
approach. They used a mouse genetically modified to make all its cells glow
green. They bred this mouse with another transgenic mouse that carries a piece
of DNA that recognises vasa and changes the colour of only those cells that
carry it. As a result, all of their offsprings' cells are green except those
containing vasa, which appear red, yellow or blue.
The group monitored the cells
that weren't green for three days. "These cells never proliferate,"
says Liu. What's more, when his team injected the non-green cells into a piece
of mouse ovary, they were not able to make eggs.
"We've found that these
cells are not really stem cells," says Liu. While the cells might look
like stem cells, they don't act in the same way, he says. "We're not sure
what they are."
Tilly stands by his discovery. He
points out that it is difficult for Liu's team to rule out his findings because
they did not use the same technique.
A different view
The gene for vasa is expressed in
cells at every stage of development, Tilly says. This might mean that the cells
that Liu's team tried to develop did not include any stem cells, which are
rare, he says.
The cells that Liu’s team found
were also about three or four time the size of those that Tilly's team identified
as stem cells. "From the results shown, Liu was working with nothing but
immature eggs, and of course they're not going to proliferate," says
Tilly.
He thinks Liu's team might have
spotted some stem cells if they had monitored the cells samples for longer.
"It takes several weeks for the cells to start growing, not three
days," he says.
Evelyn Telfer at the University of Edinburgh, UK, is also
unconvinced by Liu's findings. "They simply do not attempt to look at the
population of cells reported by the other group," she says. "They're
not comparing like-for-like, they're comparing apples and oranges." Although
the role of the stem-like cells that Tilly's group identified still needs to be
proven, Liu's team's findings don't rule out the cells' existence, says Telfer.
Hugh Clarke at
McGill University in Canada, however, is impressed with Liu's study. "It's
a really good study that's carefully done," he says. "It provides
evidence that ovarian stem cells don't exist."
Instead of settling the debate,
the new findings may only have fanned the flames. "Multiple groups have
found these [stem] cells in multiple species and yet there are still people who
refuse to believe it," says Tilly.
"I suggest we try to calm
down the hype," says Liu. "We need to wait for other labs to repeat
[Tilly's] findings before we throw money into this."
"I wouldn't waste time
looking for something that I don't think is there," says Clarke.
Tilly, however, doesn't mind if
other groups give up, because then, he says, the most exciting discoveries of
what the cells can do will be left to him and his colleagues.
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