Blastocysts in anabiosis
Researchers from the University of California at San Francisco have found a way to stop the development of mouse embryos up to one month in the laboratory. Scientists believe that their study could potentially have an impact on assisted reproductive technologies, regenerative medicine, stop aging, and cancer.
In their study, the researchers 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 the embryos in a stable and reversible state of suspended animation. Typically, the embryos may remain at the blastocyst stage in vitro not more than two days. However, therapy with mTOR inhibitors prolong this state for up to four weeks.
Lead author Aidan Bulut-Karsioglu and his colleagues demonstrated that the embryos are suspended in the development quickly resumed normal growth, when scientists stopped to introduce a regulator of cell growth inhibitors. When the embryos are returned to the body of the mother, of whom developed a healthy offspring.
The discovery came as a surprise to researchers who set out to explore how the suppression of mTOR inhibits the growth of cells of a blastocyst, and not find a way to immerse the embryos are "dormant". Subsequent experiments showed that the embryonic stem cells derived from an embryo at the blastocyst stage, as can be immersed in a state of suspended animation control cell growth inhibitors. Apparently, the drugs work by reducing the activity of the gene in most of the genome, with the exception of a few dominant genes, which themselves can inhibit 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 has recently developed Kevan Shaukat laboratory in the University of California in San Francisco.
Researchers believe that a state of suspended animation and can be extended for a longer period than 30 days. Sleeping blastocyst eventually die when they run out of stock of metabolites. If scientists find a way to supply nutrients to the culture medium, the cells will survive and longer sleep. But while researchers do not know for sure, in which specific substances need blastocyst in anabiosis.
The study showed that the resting state, in which they called the blastocyst, blocking the mTOR, was almost identical to the innate ability of the mice to stop pregnancy in the early stages. This temporary stagnation - diapause - common in many mammals, from mice to the marsupial wallaby. Since pregnant females can delay the development of the fetus, when not enough food. mTOR protein acts in such a situation the regulator terms of development, which acts as a nutritional sensor. He seemed to be "tunes" the process of cell development, relying on the level of nutrients available in the environment.
Does a person's ability to stop a pregnancy at the blastocyst stage? While this is an open question: under current conditions it is difficult to track the amount of time from fertilization to implantation, in which the formation of the blastocyst. However, there are some examples of the practice of in vitro fertilization with an unusually long period of gestation and the mismatch between the timing of artificial embryo transfer and delivery. Based on these facts, the researchers believe that people in some situations, may delay the implantation of embryos.
Research can have a big impact on the reproduction of the auxiliary, the practice is limited by the rapid degradation of the embryos, as soon as they reach the blastocyst stage. Cryostasis blastocyst can become an alternative to freezing embryos and give doctors more time to search for genetic defects before implantation.
mTOR inhibitors are in clinical trials, and subsequently could overcome some cancers. However, the results of a new study demonstrating the potential danger of such an approach: mTOR-inhibitors may slow the development of cancer and to reduce the swelling, but can not ignore "dormant" tumor cells that can be activated and spread throughout the body after a pause therapy. To kill the remaining cells have to use drugs second and third-line therapy.
Now, the authors seek to find out whether mTOR inhibitors to control stem cells in the later stages of development. Such an opportunity would help repair or replace damaged organs. Scientists believe that the findings of the study also have potential value in the study of aging.
"This is a prime example of the power of fundamental science. We are not looking for ways to stop the development of the blastocyst or simulate diapause. We did not try to create an effective therapy against cancer or to develop more efficient methods for the regeneration of tissue or organ transplants. It was all in our minds, but experiments have suggested to us that we go to something that should be understood and could not ignore, where they were "- said the head of the laboratory Miguel Rama-Santos, Associate Professor, Department of Obstetrics, Gynecology and Reproductive Sciences University of California at San Francisco.
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In theory, a similar technology cryopreservation of embryos at an early stage of development and their transportation will allow thus to colonize space. There are several different views on the way in which will be colonized. The essence is to ensure that a fully autonomous robots deliver "cargo" on the planet suitable for life, prepare all the conditions for normal existence of man there and then thawed embryos. However, researchers from the University of California in San Francisco, did not mention the fact that their discovery could contribute to the development of this concept. To put this theory into practice space colonization, require artificial uterus, which "makes" the fruit.
The scientific work is published in the journal Nature November 23, 2016
Referenced Materials:
- http://www.nature.com/nature/journal/v534/n7606/full/nature17963.html
- http://www.nature.com/nature/journal/v540/n7631/full/nature20578.html