The phrase “test-tube baby” was once a misnomer used to describe in vitro fertilization (IVF). While IVF fertilizes the eggs outside of the womb, the baby itself develops inside the uterus (abandon all sci-fi dreams of humans developing in some kind of glass egg here). Growing humans without a womb is still very much a plot for science fiction, but synthetic wombs have recently checked off a new milestone.
Set to be published in the journal Nature, a new study was able to sustain a mouse embryo outside of the womb for six days, allowing scientists to observe embryonic development in a way that has never been done before (though artificial wombs have been used to support preterm lambs). It’s hoped the unprecedented access to the early developmental stages of a mammalian embryo will reveal new insights into developmental defects and how to treat them, as well as pregnancy complications that arise during embryo implantation.
To date, a lot of what is understood about mammalian embryonic development was built upon observations of non-mammalian development, such as in fish and frogs. These species make for convenient subjects, as they lay transparent eggs, meaning the embryo is on show from day dot. However, this leaves gaps in the knowledge of mammalian development, which has been hard to determine without seeing it in the flesh, so to speak.
To begin filling these gaps in, scientists at the Weizmann Institute of Science spent several years perfecting a two-step process which – after a long stretch of trial and error – enabled the team to support a developing mouse embryo outside of the uterus for six days. Mice have an average gestation period of 20 days, at the end of which they have specialized organs and a visible body plan – the holy grail these scientists so desperately wanted to examine in detail. Six days was, however, far enough through the total gestation period to see, even with the naked eye, some advanced-stage developments in the mice embryos including a heartbeat.
Step one of the two-step process took mouse embryos at the point of development during which they’d normally be implanting into the uterus. The embryo at this stage is a ball of cells made up of 250 identical stem cells which are pluripotent, meaning they can specialize to become any kind of cell the mouse's genes code for.
This ball of potential was placed on the lab’s own-recipe growth medium, which it was able to attach to in the same way it would’ve done the uterine wall. With the embryo in place, they were able to witness it undergo the first stages of development in which it doubles and triples in size as it establishes an inner, middle, and outer layer. This step took two days.
Step two required extra support for the developing embryos, as they would next undergo the energetically expensive process of forming organs within their three layers. To provide this, the team placed the embryos into little beakers which contained a nutrient solution. Each embryo had its own beaker and was placed on a kind of developmental Ferris wheel which continually cycled to keep the nutrient solution mobile and mixing. The nutrients, gas elements, and gas pressure all needed to be maintained to keep the embryos alive, growing without the nutrients and oxygen usually supplied by maternal blood from the placenta.
Footage from the study shows mouse embryos at five days old, grown outside the uterus. They remain viable in their embryonic sac in the test tube and exhibit a visible heartbeat and blood system development.
With this new technique, the team was able to keep the embryos alive long enough to have a visible heartbeat at six days. It might sound like a small feat, but it’s the farthest such a mammalian “beaker baby” has made it, and could have huge ramifications for embryonic science and medicine. The team next hope to run their investigations without the need for real mice embryos extracted from pregnant lab animals, instead using artificial ones grown from totipotent stem cells.
[H/T: MIT Technology Review]