Thursday, October 4, 2012

Engineered Eggs

Researchers in Japan have reported success in generating mouse eggs or oocytes from pluripotent stem cells. When fertilized, these induced eggs grew into live, healthy pups capable of producing their own offspring. The work is reported in the October 5 issue of the journal Science.

The research team used two different types of pluripotent cells, embryonic and induced. In both cases, they were able to produce cells that are the precursor of the cells of the ovaries, which form eggs. Once they produced these cells and grew them in clusters, they implanted them into the bodies of female mice, where they developed into cell structures that functioned like ovaries. From these reconstituted ovaries, researchers harvested mature oocytes, much as they would for in vitro fertilization (IVF).

The next step, predictably, was to fertilize these eggs and implant them in surrogate mother mice. Once born, the pups developed and were allowed to breed, producing viable offspring.

Pups from ES-oocyte. Female offspring from primordial germ cell-like cell-derived oocytes were fully fertile. Courtesy of Katsuhiko Hayashi.

The most immediate impact of this research will be to advance our understanding of the fundamentals of reproductive biology, especially the development of egg cells. If similar strategies will work with human pluripotent stem cells—especially induced cells—this research may open new approaches for reproductive medicine in the years ahead.

What other possibilities might there be? Again, if the work can be replicated in human beings, two things might happen. Somewhat more remote is the possibility that this strategy will be used for the purposes of human germline modification or so-called “designer babies.” For example, pluripotent stem cells might be genetically modified before they are induced to become the source of oocytes. The modification could be to avoid a disease or for the purposes of enhancement.

More likely, of course, is that this strategy will be used to create human oocytes for research purposes. For example, human induced ovary-like cells could be implanted into a mouse or other nonhuman animal, grown to the right stage of development, then “harvested” in order to collect a significant number of oocytes.

Today, research in certain areas is hampered because of limited supplies of human oocytes. One area that comes to mind is nuclear transfer or cloning. While “Dolly” the sheep is now only a distant memory, this advance brings closer the possibility that with an ample supply of human oocytes for experimentation, researchers will learn how to create human clones reliably.

So the big question is whether this research can be replicated in humans. On that point, here's how the article concludes: "our system serves as a robust foundatin to investige and further reconstitution femaile germline development in vitro, not only in mice, but also in other mammals, including humans."

The article, entitled "Offspring from Oocytes Derived from in vitro Primordial Germ Cell-like Cells in Mice," appears in the 5 October 2012 issue of the journal, Science.

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