Embryos development 'paused' for upto a month
Los Angeles, Nov 24 Scientists have found a way to pause the development of early mouse embryos for up to a month in the lab - and later resume normal growth - a finding with potential implications for assisted reproduction, ageing and even cancer.
The research involved experiments with pre-implantation mouse embryos, called blastocysts.
Researchers from University of California, San Francisco in the US found that drugs that inhibit the activity of a master regulator of cell growth called mTOR can put these early embryos into a stable and reversible state of suspended animation.
"Normally, blastocysts only last a day or two, max, in the lab. But blastocysts treated with mTOR inhibitors could survive up to four weeks," said Aydan Bulut-Karslioglu, a postdoctoral researcher at UCSF.
Researchers showed that paused embryos may quickly resume normal growth when mTOR inhibiters were removed, and developed into healthy mice if implanted back into a recipient mother.
The discovery was a surprise to the researchers, who had intended to study how mTOR-inhibiting drugs slow cell growth in blastocysts, not to find a way to put the embryos into hibernation.
"To put it in perspective, mouse pregnancies only last about 20 days, so the 30-day-old 'paused' embryos we were seeing would have been pups approaching weaning already if they'd been allowed to develop normally," said senior author Miguel Ramalho-Santos from UCSF.
Further experiments demonstrated that cultured mouse embryonic stem cells - which are derived from the blastocyst-stage embryo - can also be put into suspended animation by mTOR inhibitors.
The drugs appear to act by reducing gene activity across much of the genome, the team found, with the exception of a handful of so-called "repressor" genes that themselves may act to inhibit gene activity.
The researchers tested a number of different mTOR inhibitors and found that the most effective was a new synthetic drug called Rapa-Link that was recently developed at UCSF by the lab of Kevan Shokat.
The researchers believe that it should be possible to extend the suspended animation for much longer than the 30 days observed in the present study.
"Our dormant blastocysts are eventually dying when they run out of some essential metabolite within them. If we could supply those limiting nutrients in the culture medium, we should be able to sustain them even longer," said Bulut-Karslioglu.
Researchers showed that the dormant state they were able to induce in blastocysts by blocking mTOR was almost identical to the natural ability of mice to pause a pregnancy in its early stages.
This temporary stasis, called diapause, occurs in species across the animal kingdom, and in mammals from mice to wallabies, it typically allows mothers to delay pregnancy when food is scarce or they are otherwise stressed. The study was published in the journal Nature.