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The development of most mammals is usually hidden in the mother's womb, protected from predators and scientists. A new technique developed by researchers at the Weizmann Institute of Science in Israel allows mouse embryos to grow in a carefully controlled environment in a transparent glass bottle outside the uterus. The team described the method in the journal Nature on Wednesday (March 17).
"The holy grail of developmental biology is to understand how a single cell, a fertilized egg, can make all the specific types of cells in the human body and grow into 40 trillion cells," said Paul Tesar, a developmental biologist at Case Western Reserve University. Medicine who was not involved in the study told the New York Times. "From the very beginning, researchers have been trying to find ways to answer this question."
Traditionally, surgical snapshots are used to view the formation of different tissues and features during mouse embryonic development. At different stages of development, the uterus is cut open to observe the developing pups, and is eventually destroyed in the process. By transferring embryos to a uterus-like environment, development can be monitored in real time while keeping the embryo sac intact.
To accomplish this task, the team removed the embryos from the mother mouse at about the same time as the embryos were implanted in the uterus. When placed on a growth medium in a petri dish, the embryo's placenta develops.
The uterus is a dynamic organ that changes the embryo's environment as the embryo's needs change throughout the pregnancy. Therefore, the conditions of laboratory manufacturing also need to be adapted. After being placed in a petri dish for two days, the embryos were transferred to the nutrient solution in a glass beaker, and the beaker was gently rotated to allow nutrients to flush out the embryo. Researchers ensure that the embryo has the correct gas and pressure mix in the beaker. Beaker embryos are regularly compared with naturally developed embryos, and the progress at each stage is the same.
"If you give an embryo the right conditions, its genetic code will work like a set of pre-set dominoes, falling one after another," co-author Jacob Hannah in a news article Said in the draft. "Our goal is to recreate these conditions. Now we can observe the collision of each domino with the next domino in real time."
The embryo is on the 11th day of the 20 days of pregnancy (E11.0). Six of these days occurred in the glass uterus. After that, they became too big and needed blood vessels connected to the placenta to transport nutrients and oxygen. At this stage, they can clearly see the beating heart outside the beaker, as well as the limb buds, the digestive system, and the initial stages of the auditory and visual systems.
The researchers will next try to create embryos without uterus by fertilizing the eggs in the laboratory. Nevertheless, an artificial blood supply is still needed to keep the embryos growing to the end.
"This laid the foundation for other species," Hanna told MIT Technology Review. "I hope it will allow scientists to cultivate human embryos to the fifth week," which is roughly the same developmentally as the mouse E11.5.
Hannah said that being able to see human embryos at the earliest stage is of great help in determining why birth defects occur or why some embryos are not implanted in the uterine wall.
"[In the future] we may have the ability to develop human embryos from fertilization to childbirth completely outside the womb, which is not unreasonable," Tesar told the New York Times.
The authors say that in addition to having a front-row seat for embryonic development, this technology can ultimately save time and money by conducting the same research faster and with fewer animals.
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