Imma Perfetto
Cosmos science journalist
The mechanisms that allow some mammals to pause the development of their young inside the womb also seem work in human cells, according to a fascinating new study published in the journal Cell.
Biologists discovered they could induce a dormant state in human cells by decreasing the activity of the mTOR signaling pathway, which they previously showed is a major regulator of this process in mice.
They triggered this dormant state not in human embryos, but in human pluripotent stem cells and stem-cell based models known as blastoids, which mimic the blastocyst stage of embryonic development at about 5 days post-fertilisation.
The researchers think that humans might have an inherent mechanism to temporarily slow down their development like other mammals, though this may not be used during pregnancy.
“This potential may be a vestige of the evolutionary process that we no longer make use of,” says Nicolas Rivron, co-senior author of the paper from the Austrian Academy of Sciences.
“Although we have lost the ability to naturally enter dormancy, these experiments suggest that we have nevertheless retained this ability and could eventually unleash it.”
More than 130 mammalian species can temporarily slow embryo development to improve the chances of survival for both embryo and mother in a process called embryonic diapause.
This mechanism usually happens at the blastocyst stage, just before the embryo implants in the uterus. During diapause, the embryo remains free-floating, and pregnancy is extended for weeks or months until conditions are more favourable and development resumes.
Not all mammals use diapause as a reproductive strategy, but researchers have shown that the blastocysts of more mammals still retain the capacity to enter a dormant state if they receive the right triggers.
Until now it was unclear whether diapause could be triggered in humans.
“The mTOR pathway is a major regulator of growth and developmental progression in mouse embryos,” says co-senior author Aydan Bulut-Karslioglu of the Max Planck Institute for Molecular Genetics in Germany.
“When we treated human stem cells and blastoids with an mTOR inhibitor we observed a developmental delay, which means that human cells can deploy the molecular machinery to elicit a diapause-like response.”
Cells in this dormant state show reduced cell division, slower development and a decreased ability to attach to the uterine lining. The ability to enter this dormant stage seems to be restricted to the blastocyst stage of development.
“The developmental timing of blastoids can be stretched around the blastocyst stage, which is exactly the stage where diapause works in most mammals,” says first author Dhanur P. Iyer, from the Max Planck Institute for Molecular Genetics and Freie Universität Berlin.
The dormancy was also reversible and blastoids resumed normal development when the mTOR pathway was reactivated.
The discovery could have important implications for reproductive medicine.
“On the one hand, undergoing faster development is known to increase the success rate of in vitro fertilization (IVF), and enhancing mTOR activity could achieve this,” says co-senior author of the study Nicolas Rivron of the Austrian Academy of Sciences.
“On the other hand, triggering a dormant state during an IVF procedure could provide a larger time window to assess embryo health and to synchronise it with the mother for better implantation inside the uterus.”
