By inhibiting a series of chemical reactions known as the mTOR signaling pathway, scientists have found a way to hit the “pause” button on human body development to treat various chronic diseases.
Research conducted by scientists from the Aydan Bulut-Karslıoglu Laboratory at the Max Planck Institute for Molecular Genetics in Berlin, Germany, and the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences has recently been published in the September 2024 issue of the journal Cell.
The study identifies the molecular mechanisms controlling the hibernation phase of embryos that science can potentially influence in human cells.
In some mammalian species, the timing of continuous embryonic development can be altered to enhance the survival chances of both the embryo and the mother. This mechanism temporarily slows down the development process, known as the hibernation state of the embryo, which typically occurs at the blastocyst stage, just before the embryo implants in the uterus.
Discovering the pause button helps us understand many mysteries about the human body.
During the hibernation phase, the embryo remains suspended and the pregnancy is extended. This hibernation state can be maintained for several weeks or months before development resumes under favorable conditions.
Although not all mammalian species utilize this reproductive strategy, the ability to pause development can be experimentally activated. Whether human cells can respond to agents that induce a hibernation state remains an unanswered question.
In the study, the researchers did not experiment on human embryos but used human stem cells and stem cell-based blastocyst models known as blastocysts. These blastocysts provide a scientific and ethical alternative to using embryos for research.
The research discovered that modifying a specific molecular chain, the mTOR signaling pathway, in these stem cell models induces a hibernation state very similar to that occurring during the hibernation phase.
“The mTOR pathway is a key regulator of development and progression in mouse embryos. When we treated human stem cells and embryos with mTOR inhibitors, we observed slowed development, meaning human cells can deploy the molecular machinery to trigger a hibernation-like response,” said Aydan Bulut-Karslıoglu, a member of the research team.
This hibernation state is characterized by reduced cell division, slower growth, and decreased ability to adhere to the uterine lining. Importantly, the ability to enter hibernation appears to be limited to a short developmental window.
“The embryonic development time can be extended around the blastocyst stage. This is precisely the stage where hibernation occurs in most mammalian species. Moreover, this hibernation condition can be reversed, and the embryo can continue to develop normally when the mTOR pathway is reactivated. The ability to alter the timing of embryonic development has implications for IVF,” stated Nicolas Rivron, the research team leader.
According to Nicolas Rivron, like other mammals, the human body possesses an inherent mechanism to temporarily slow its development, although this mechanism may not be utilized during pregnancy.
“This potential is a remnant of an evolutionary process that we no longer utilize. Although we have lost the natural ability to enter a hibernation state, experiments show that we still maintain this internal capability and may eventually be able to unlock it,” he added.
For basic research, the question arises as to whether human and other mammalian cells can enter a hibernation state through similar or alternative pathways and utilize it for the same purpose, such as pausing or timing their development and implantation.
While researchers are optimistic about how this work may be applied in the future, the current findings allow us to explore many more fascinating aspects of the human body.
