The mouse embryos looked perfectly normal. All their organs were developing as expected, along with their limbs and circulatory and nervous systems. Their tiny hearts were beating at a normal 170 beats per minute.
But these embryos were not growing in a mother mouse. They were developed inside an artificial uterus, the first time such a feat has been accomplished, scientists reported.
The experiments, at the Weizmann Institute of Science in Israel, were meant to help scientists understand how mammals develop and how gene mutations, nutrients and environmental conditions may affect the fetus. But the work may one day raise questions about whether other animals should or could be cultured outside a living womb.
In a study published in the journal Nature, Dr. Jacob Hanna described removing embryos from the uteruses of mice at five days of gestation and growing them for six more days in artificial wombs.
At that point, the embryos were about halfway through their development; full gestation is about 20 days. Hanna and his colleagues have grown more than 1,000 embryos.
Alexander Meissner, director of genome regulation at the Max Planck Institute for Molecular Genetics in Berlin, said that "getting this far is amazing" and that the study was "a major milestone."
Hanna said he and his colleagues had taken fertilized eggs from the oviducts of female mice just after fertilization — at Day 0 of development — and had grown them in the artificial uterus for 11 days.
"The holy grail of developmental biology is to understand how a single cell, a fertilized egg, can make all of the specific cell types in the human body and grow into 40 trillion cells," Tesar said.
What was needed was a way to get inside the uterus, watching and tweaking development. Hanna spent seven years developing a two-part system that includes incubators, nutrients and a ventilation system. The mouse embryos are placed in glass vials inside incubators, where they float in a nutrient fluid.
The vials are attached to a wheel that slowly spins so the embryos do not attach to the wall, where they would become deformed and die. The incubators are connected to a ventilation machine.
At Day 11, Hanna and his colleagues examined the embryos and compared them to those developing in the uteruses of living mice. The lab embryos were identical, the scientists found.
The artificial womb may allow researchers to learn more about why pregnancies end in miscarriages or why fertilized eggs fail to implant. It opens a new window onto how gene mutations or deletions affect fetal development.
The work is "a breakthrough," said Magdalena Zernicka-Goetz, professor of biology and biological engineering at the California Institute of Technology. It "opens the door to a new age of studying development in the experimental mouse model."