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Eggs Created in Dish Produce Mouse Pups

4 October 2012 2:10 pm
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Mitinori Saitou and Katsuhiko Hayashi

Who's your mommy? These adult mice grew from oocytes, or immature eggs, derived in vitro from induced pluripotent stem cells.

Want baby mice? Grab a petri dish. After producing normal mouse pups last year using sperm derived from stem cells, a Kyoto University team of researchers has now accomplished the same feat using eggs created the same way. The study may eventually lead to new ways of helping infertile couples conceive.

"This is a significant achievement that I believe will have a sustained and long-lasting impact on the field of reproductive cell biology and genetics," says Amander Clark, a stem cell biologist at University of California, Los Angeles.

The stem cells in both cases are embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. The former are taken from embryos and the latter are adult tissue cells that are reprogrammed to act like stem cells. In theory, both can produce all of the body's cell types, yet most researchers have been unable to turn them into germ cells, precursors of sperm and eggs.

The Kyoto group, led by stem cell biologist Mitinori Saitou, found a process that works. As with the sperm, the group started with ES and iPS cells and cultured them in a cocktail of proteins to produce primordial germ cell-like cells. To get oocytes, or precursor egg cells, they then mixed the primordial cells with fetal ovarian cells, forming reconstituted ovaries that they then grafted onto natural ovaries in living mice. Four weeks and 4 days later, the primordial germ cell-like cells had developed into oocytes. The team removed the ovaries, harvested the oocytes, fertilized them in vitro, and implanted the resulting embryos into surrogate mothers. About 3 weeks later, normal mouse pups were born, the researchers report online today in Science.

"It is remarkable that one can produce oocytes capable of sustaining complete development starting with embryonic stem cells," says Davor Solter, a developmental biologist at Singapore's Institute of Medical Biology. Clark adds that the immediate impact of the work will be on understanding the molecular mechanisms involved in forming germ cells. Saitou says that with a bit more progress in understanding the complex interactions at work, they may be able to coax the cells through the entire oocyte development process in a lab dish. If successful, "we may be able to skip the grafting," he says.

Further in the future, the technique could lead to a new tool for treating infertility. "This study has provided the critical proof of principle that oocytes can be generated from induced pluripotent stem cells," Clark says. If applied to humans, it could lead to the ability to create oocytes from iPS cells taken from infertile women. But Saitou cautions that moving on to human research will require resolving thorny ethical issues and technical difficulties. Solter says that at the extreme, the new approach could lead to the production of human embryos from cell lines and tissue samples. Still, he notes, "defining the status of such 'parentless' human embryos and the biological, ethical, and legal issues they will raise defies the imagination."

*Correction 11:35 a.m., 6 December: The headline of this item has been corrected to reflect that the sperm used to fertilize the eggs was not created in a dish, as the previous headline implied.

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