Embryos in suspended animation

Researchers put mouse embryos in suspended animation for a month without negative consequences

Anastasia Krasnianskaya, Geektimes

Researchers from the University of California at San Francisco have found a way to suspend the development of mouse embryos for up to one month in the laboratory. Scientists are confident that their research could potentially have an impact on assisted reproductive technologies, regenerative medicine, stop aging and cancer.

In their study, the scientists conducted an experiment with embryos at an early stage of development, called blastocysts. They found that drugs that inhibit the activity of the main regulator of cell growth, the mTOR protein, can immerse embryos in a stable and reversible state of suspended animation. As a rule, embryos can remain at the blastocyst stage in the laboratory for no more than two days. But therapy with mTOR inhibitors prolongs this condition up to four weeks.

The lead author of the study, Aidan Bulut-Karsioglu, and his colleagues demonstrated that embryos suspended in development quickly resumed normal growth when scientists stopped injecting inhibitors of the cell growth regulator. When the embryos were returned to the mother's body, healthy offspring developed from them.

The discovery came as a surprise to researchers who intended to study how mTOR suppression slows down the growth of blastocyst cells, rather than find a way to put embryos "into hibernation". Subsequent experiments have shown that embryonic stem cells obtained from an embryo at the blastocyst stage can also be put into a state of suspended animation by inhibitors of the cell growth regulator. Apparently, the drugs act by reducing the activity of a gene in most of the genome, with the exception of a few dominant genes, which themselves can suppress the activity of others. The researchers tested a number of different mTOR inhibitors and found that the most effective is a new synthetic drug Rapa-Link, which was recently developed by the laboratory of Kevan Shokat at the University of California, San Francisco.

Researchers believe that the state of suspended animation can be extended for a longer period than 30 days. Dormant blastocysts eventually die when they run out of metabolites. If scientists find a way to supply nutrients to the culture medium, the cells will survive longer hibernation. But so far, researchers do not know for sure what specific substances blastocysts need in suspended animation.

The study authors demonstrated that the resting state they induced in the blastocyst by blocking mTOR was almost identical to the mice's innate ability to suspend pregnancy in the early stages. This temporary stagnation – diapause – occurs in many mammals, from mice to marsupial wallabies. So pregnant females can delay the development of the fetus when there is not enough food. In such a situation, the mTOR protein acts as a regulator of the timing of development, which works as a nutrient sensor. It kind of "adjusts" the process of cell development, relying on the level of nutrients available in the environment.

Does a person have the ability to suspend pregnancy at the blastocyst stage? So far, this is an unresolved issue: in modern conditions, it is difficult to track the time interval from fertilization to implantation, in which the formation of a blastocyst occurs. However, there are some examples from the practice of in vitro fertilization (IVF) with an unusually long pregnancy period and a discrepancy between the timing of artificial embryo transfer and childbirth. Based on these facts, researchers believe that people in some situations may delay the implantation of embryos.

The study can have a great impact on assisted reproduction, the practice of which is limited to the rapid degradation of embryos as soon as they reach the blastocyst stage. Anabiosis of the blastocyst can be an alternative to freezing embryos and will give doctors more time to search for genetic defects before implantation.

mTOR inhibitors are undergoing clinical trials, and in the future could overcome some types of cancer. However, the results of a new study demonstrate the potential danger of this approach: mTOR inhibitors can slow down the development of cancer and shrink tumors, but they can ignore "dormant" cancer cells that can activate and spread through the body after therapy is suspended. To kill the remaining cells, you will have to use drugs of the second and third line of therapy.

Now the authors are trying to find out whether mTOR inhibitors can control stem cells at later stages of development. Such an opportunity would help to restore or replace damaged organs. Scientists are confident that the data obtained during the study also have potential significance in the study of aging.

"This is a vivid example of the power of fundamental science. We weren't looking for ways to stop blastocyst development or simulate diapause. We have not tried to create an effective therapy against cancer or to develop more effective methods for tissue regeneration or organ transplantation. All this was in our minds, but the experiments told us that we were going to something that we had to understand and could not ignore where they led," said the head of the laboratory, Miguel Ramalo-Santos, associate professor of Obstetrics, Gynecology and Reproductive Sciences at the University of California, San Francisco (in a press releasein the release of Researchers Put Mouse Embryos in Suspended Animation – VM).

In theory, a similar technology of cryopreservation of embryos at an early stage of development and their transportation will thus allow colonizing space. There are several different views on how colonization will be carried out. The essence boils down to the fact that fully autonomous robots will deliver the "cargo" to a planet suitable for life, prepare all the conditions for a normal human existence there, and then unfreeze the embryos. However, researchers from the University of California at San Francisco did not mention that their discovery could contribute to the development of this concept. To bring this theory of space colonization to life, an artificial womb will be required, which "bears" the fetus.

The scientific work was published in the journal Nature (Bulut-Karslioglu et al., Inhibition of mTOR induces a paused pluripotent state).

Portal "Eternal youth" http://vechnayamolodost.ru  30.11.2016