This research could lay the foundations for improving in vitro fertilization success rates as well as creating new and improved non-hormonal contraception.
A group of embryologists took another step in modeling early human development: they managed not only to create an embryo from stem cells but also to simulate its implantation into the wall of the uterus.
True, this happened only in a test tube – therefore, instead of the uterus, they used an endometrial organoid, and the implanted embryo could not develop normally.
Nevertheless, this shows that the artificial human embryos had many of the properties of real embryos, and they can be used as a model, for example, in the development of contraceptives.
Scientists create artificial human embryos from stem cells: Everything you need to know
Early stages of human development
Exploring the early stages of human development is very difficult — two problems stand in the way. Firstly, there are no available embryos: in the first weeks, women often do not know that they are pregnant, and, even if they want to, do not have time to have an abortion. And working with “extra” embryos that remain, for example, after IVF, is not allowed in all countries.
Secondly, such embryos are difficult to grow: at the end of the first week, they must be implanted into the uterine wall in order to develop normally further. This stage has not yet been reproduced in vitro, so researchers have to simulate it using different substrates and signaling substances. As a result, even if the embryo continues to develop, it still turns out to be unlike a real embryo – at least in its geometry.
Creating human embryos from stem cells
A group of scientists led by Nicolas Rivron from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences was lucky not to face the first problem: they worked with a culture of stem cells from a donor embryo left after IVF (parents donated it for research). Armed with these cells, they tried to solve the second problem and create an embryo that would look like a real one and could be implanted into a model uterus in vitro.
Process
To do this, the researchers placed the cells in hydrogel wells, where they formed compact spheres. They were then treated with inhibitors of three signaling pathways, Hippo, TGF-β, and ERK. As a result, the cells that were on the surface of the spheres turned into trophectoderm – a dense layer of cells from which extraembryonic tissues are subsequently formed.
They started pumping water into the sphere and turned it into a cell ball with a cavity inside. This is what the embryo looks like by the end of the first week of development, this stage is called the blastocyst.
At the same time, inside all blastoids (as the researchers called their result), two groups of cells spontaneously emerged, resembling primitive endoderm (another future extraembryonic tissue) and an epiblast (the embryo itself, which is then used to form all body tissues).
The authors of the work disassembled the blastoids into individual cells and verified that these three types of cells, in terms of the set of working genes, are really similar to their counterparts from ordinary embryos. No more types were found in blastoids – with the exception of analogs of the amnion, a later extraembryonic tissue, but no more than 3 percent were counted.
Ability to implant
After that, the scientists checked whether their blastoids retain the main property of the blastocyst – the ability to implant. To do this, they planted blastoids on endometrial organoids – groups of cells that mimic the structure of the uterine wall. It turned out that blastoids can successfully attach to the endometrium.
At the same time, the blastoids, from which the epiblast was removed, leaving only extraembryonic tissues, could not be implanted. Likewise, they did not attach to the endometrium, which was not activated by female sex hormones. Thus, they reproduced all the basic mechanisms of implantation quite accurately.
How did the human embryos look at the end of the experiment?
The researchers left the attached embryos to grow on the endometrium for several more days. Their extraembryonic tissues have grown and even began to produce chorionic gonadotropin, a hormone, the concentration of which in a woman’s blood determines pregnancy in the early stages. But the embryonic part itself, although it remained alive, did not look like real embryos, and on the 13th day, the experiment was stopped.
This is not the first study to collect blastoids from stem cells. Moreover, before they could be created even from non-embryonic stem cells. But until now, no one has tested them for their implantation ability. The next step should be to improve the model, which will allow the embryonic part of the blastoids to develop further.
In the meantime, the authors of the work promise that their model could be useful in the development of media for the cultivation of embryos (they are used, for example, in IVF) – and the verification of contraceptive drugs that block the attachment of the blastocyst to the uterus.
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Sources:
• The Independent. (2021, December 2). Human embryo models research may pave the way for improved IVF rates – study.
• Kagawa, H., Javali, A., Khoei, H. H., Sommer, T. M., Sestini, G., Novatchkova, M., Scholte op Reimer, Y., Castel, G., Bruneau, A., Maenhoudt, N., Lammers, J., Loubersac, S., Freour, T., Vankelecom, H., David, L., & Rivron, N. (2021, December 2). Human blastoids model blastocyst development and implantation. Nature News.
• Massey, N. (2021, December 2). Human embryo models research may pave the way for improved IVF rates – study.
• Ungar, L. (2021, December 2). Scientists use stem cells to create models of pre-embryos. AP NEWS.
