Most mammalian development typically happens tucked away inside of a mother’s uterus, protected from predators and the prying eyes of scientists. A new technique developed by researchers at the Weizmann Institute of Science in Israel allows a mouse embryo to grow in a carefully controlled environment within clear glass bottles, outside of the uterus. The team described the method Wednesday (March 17) in Nature.
“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,” developmental biologist Paul Tesar of Case Western Reserve University School of Medicine who was not involved in the research tells The New York Times. “Since the beginning of time, researchers have been trying to develop ways to answer this question.”
Traditionally, seeing how the different tissues and features form during embryonic development in mice is done through surgical snapshots. At different stages in development, the womb is cut open to observe the developing pup, which ultimately is destroyed in the process. By transferring the embryo to a uterine-like environment, development can be monitored in real-time while keeping the embryonic sac intact.
To accomplish the task, the team retrieved embryos from a mother mouse right around the same time they were due to implant in the uterus. When placed atop a growth medium in a dish, the embryos’ placentas developed.
The uterus is a dynamic organ, altering the embryo’s environment as its needs change throughout gestation. As such, the lab-made conditions needed to adapt as well. After two days in the dish, the embryos were moved to a nutrient solution in glass beakers that rotated gently, allowing the nutrients to wash over the embryos. The researchers made sure that the embryos had the correct mix of gases and pressure inside the beaker. The beaker embryos were periodically compared to those developing naturally and the progress was identical at every stage.
“If you give an embryo the right conditions, its genetic code will function like a pre-set line of dominos, arranged to fall one after the other,” coauthor Jacob Hanna says in a press release. “Our aim was to recreate those conditions, and now we can watch, in real time, as each domino hits the next one in line.”
The embryos made it to day 11 (E11.0) of the 20 it takes a pup to gestate. Six of those days took place inside the glass wombs. After that, they became too large and needed a bloodline connected to the placenta to deliver nutrients and oxygen. At this stage, they had beating hearts that could be clearly seen outside of the beaker, along with limb buds, digestive systems, and the beginning stages of auditory and visual systems.
The researchers will next try to create embryos completely without a uterus by fertilizing an egg in the lab. Still, an artificial blood supply would be needed to keep an embryo growing to the end.
“This sets the stage for other species,” Hanna tells MIT Technology Review. “I hope that it will allow scientists to grow human embryos until week five,” which is developmentally about the same as E11.5 for a mouse.
Hanna says being able to see a human embryo in its earliest stages could go a long way in determining why birth defects occur or why some embryos don’t implant into the uterine wall.
“It is not unreasonable that [in the future] we might have the capacity to develop a human embryo from fertilization to birth entirely outside the uterus,” Tesar tells the Times.
On top of having a front-row seat to embryonic development, the authors say, this technique could ultimately become a time- and money-saver by doing the same research faster and with fewer animals.