Embryos pause development when nutrients are low — and now we know how

The embryos of many species can stop developing when starved of nutrients, only to restart the process once these are restored – and scientists may have figured out how they do it.

In the early stages of pregnancy, a fertilised egg turns into a blastocyst, a tiny cluster of dividing cells. This then implants into the uterine wall, eventually differentiating into the various organ tissues of a fetus.

When some animals face extreme circumstances, such as when food is scarce or when it is really cold, blastocysts pause their growth and enter a state of dormancy called embryonic diapause. This can last for several months in some species, with activity resuming once conditions improve. “It is a strategy to maximise the reproductive process and thus the number of young born and their survival,” says Bruce Murphy at the University of Montreal in Canada, who wasn’t involved in the research.

Now, Jiajia Ye at the Chinese Academy of Science and his colleagues have uncovered how an embryo can tell when to stall development.

They put 14 newly pregnant mice in a cage with food and 11 others in a cage without food. After 3.5 days, they found that the blastocysts of the well-fed mice developed as usual, but those of the starved mice hadn’t implanted in the uterus, indicating embryonic diapause.

When these dormant blastocysts were then transplanted into the uteruses of well-fed mice, they started growing again.

In another part of the experiment, the researchers grew mouse embryos in petri dishes with different nutrients. They found that embryonic diapause seems to be caused by a lack of carbohydrates and proteins, while embryos exposed to normal levels of these nutrients grow as expected.

Closer inspection revealed that a sensor called Gator1 in the blastocysts can detect drops in carbohydrate and protein levels in the uterus. This then prevents a molecule that controls protein synthesis from being activated, which is necessary for blastocyst development.

When the team injected the uteruses of pregnant mice that had been deprived of food with the necessary carbohydrates and proteins, embryonic growth resumed.

With a similar proces expected to occur in human embryos, Ye hope these findings could eventually be used to improve fertility treatments. Prior to in-vitro fertilisation (IVF), embryos are sometimes preserved by freezing, then transplanted into a uterus. This method of preservation is expensive and the embryos don’t always survive the thawing process. The team has shown it could be possible to preserve them through nutrient depletion, says Ye.