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Disease and treatment

Synthetic embryos created in the lab could help manage pregnancy more effectively

Human pregnancies fail two thirds of the time because the very early embryo does not attach to the lining of the uterus. Nevertheless, very little is known about why this happens. Now a group of researchers has successfully created synthetic embryos from mouse stem cells in the laboratory. These model embryos resemble natural ones and open avenues to understanding the first and hidden processes of life and revealing the minor flaws that contribute to diseases during adult life or lead to infertility.

The tiny blob of about 100 cells is scarcely a hair’s breadth but comprises a highly organized and communicative network of cells. This is crucial, because if the coordination between the cells fails, then life takes a suboptimal path or ends. Although these early stages are critical, very little is known about them. Now a group of researchers has successfully recapitulated the process in a dish, using stem cells, which enables them to observe and understand the embryo in great detail.

“Both the inner embryonic stem cells and the outer placental stem cells can be cultured and studied in the laboratory, but now, by placing them in specific conditions, we managed to make them talk again and self-organize into an early embryo,” explains main author Nicolas Rivron, Principal Investigator, Hubrecht Institute and MERLN Institute, the Netherlands.

Understanding the conversation within the embryo

Researchers have been trying to achieve this for decades, which is why Nature published the breakthrough. The unique technique refined by Nicolas Rivron and colleagues enables small numbers of cells to be pooled and inductive cocktails of signalling chemicals to be systematically tested. These initial conditions trigger the cells to talk again.

“The fantastic thing is that we can now see them communicating and exchanging signals to spontaneously form a structure that is remarkably similar to a natural mouse embryo – with the key difference that it does not develop into an actual mouse.”

When transferred into the uterus of a mouse, the synthetic embryos correctly attached, and the lining of the uterus formed a cocoon around it to initiate the pregnancy.

The researchers do not have any ambitions of creating artificial mice or men. Their aim is to understand what is needed for an embryo to form and grow by using realistic in vitro model systems: for example, to understand which genes must be activated for the cells to divide, organize and then attach firmly to the lining of the uterus.

“Our system enables us to measure the nature and function of the signals that cells send to one another and how this affects whether the embryo attaches in utero or not. We had actually expected that the outer placental stem cells would be the ones taking care of the inner embryonic cells, the expected function of the (future) placenta. But our measurements showed the opposite: it is the embryonic stem cells that send numerous signals to guide the placental stem cells to multiply, to organize and to attach to the lining of the uterus.”

Testing the medicines for family planning and empowerment

Understanding these fundamental concepts sheds new light on why these processes can sometimes go wrong. In the long term, the researchers hope to apply what they learned to the human situation: for example, to propose new solutions to problems of contraception and infertility or to improve in vitro fertilization treatments.

“We need better options for women to decide whether they want to have a child and when. This possibility to choose strongly affects women’s health, education and career along with the children and the stability of the couple.”

Around the world, pregnancy is not always a choice, and both the World Health Organization and the Bill & Melinda Gates Foundation rank family planning as a top global health challenge that needs to be addressed to achieve equality. For instance, new contraceptives with limited side-effect and better adapted to populations are necessary. In addition, the increased participation of women in the labour force has delayed their wish to have children and has led to a sharp decrease in fertility.

“Women must be able to better plan their pregnancy without decreasing their chance of having a child. Altogether, family planning is a huge lever to secure women’s health and self-determination while supporting the development of communities. As we know, more than ever, global women’s empowerment is a necessity, and new science might help.”

In May 2018, Nicolas Rivron gave a presentation at the Copenhagen Bioscience Conferences, a Novo Nordisk Foundation initiative. “Blastocyst-like structures generated solely from stem cells” was published in Nature in May 2018.

Nicolas Rivron
Assistant Professor
Our laboratory gathers scientists and engineers developing novel model systems of organs and organisms to investigate the design principles governing development. My general interests are in understanding how genetically encoded molecular programs yield the organisation into complex multicellular structures. I began my research career studying how the cells of blood vessels sense their chemical and physical environments to organize. My research has then shifted towards the utilization of stem cells to study how the early embryo forms. This led to the in vitro formation of the blastoid, a synthetic blastocyst with the potential to implant in utero. Our research is grounded in fundamental stem cell biology using mouse and human embryonic and reprogrammed stem cells and in technologies using high throughput screenings in microsystems, single molecule imaging and single cell RNA sequencing in 3D model systems, organs and mouse embryos. Along with our epidemiologist, geneticist and clinician collaborators, we aim at using stem cell-based embryos to tackle the global health problems of infertility and understand the embryonic origin of chronic diseases.