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No uterus, no problem: Mouse embryos grown in bottles form organs and limbs

Developmental biologists have devised a method for growing mouse embryos outside a uterus for longer than ever before, giving them an unprecedented view of how mammalian organs and limbs form—a process previously hidden inside a mother’s body. Researchers in Israel report today that the new system, which includes rotating bottles filled with nutrients, kept the mouse embryos alive from roughly day five of development until day 11, about halfway through the animals’ 20-day gestation. By that time the embryos have formed hind limbs and all their major organs.

“It looks very spectacular,” says Max Planck Institute for Molecular Genetics developmental biologist Alexander Meissner, who was not involved in the work. “The fact that [the researchers] can culture these embryos and keep them alive for such a long time—it’s amazing.”

To develop the new technique, Weizmann Institute of Science developmental biologist Jacob Hanna and his colleagues engaged in more than 7 years of trial and error. Previously, scientists could grow mouse embryos in the lab for the first 3 or 4 days of development. In normal mouse pregnancies, when the embryo implants in the wall of the uterus, the placenta starts to form, and the embryo’s cells start to differentiate into more specific types of stem cells that will form different tissues. Beyond that point, it was difficult to grow developing mouse embryos outside the uterus for more than a day or two.

But the new system increased that time by nearly 1 week, Hanna and colleagues report today in Nature. Beyond nutrients in which they bathed embryos, the rotating glass bottles helped provide the tiny embryos with sufficient oxygen and atmospheric pressure. Keeping the air pressure and oxygen saturation at the right levels was the hardest part, Hanna says. “We learned how to control the ventilation system,” he adds with a laugh.

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