Home Career An early embryo is in the driver’s seat — ScienceDaily

An early embryo is in the driver’s seat — ScienceDaily


It is often thought that the early embryo is fragile and needs support. However, in the earliest stages of development, it has the power to nourish the future placenta and instructs the uterus so that it can nest. Using “blastoids,” in vitro embryo models formed with stem cells, IMBA’s Nicolas Rivran’s lab showed that the earliest molecular signals that induce placental development and prepare the uterus come from the embryo itself. The findings, published in Cell Stem Cell, may contribute to a better understanding of human fertility.

Who takes care of whom at the beginning of life? The placenta and uterus nurture and protect the fetus. But the situation at the earliest stage of development, when the blastocyst is still floating in the uterus, was still unclear. Now the research group of Nicolas Rivron from IMBA (Institute for Molecular Biotechnology of the Austrian Academy of Sciences) has revealed the basic principles of early development using blastoids.

Blastoids are in vitro models of the blastocyst, a mammalian embryo in the first few days after fertilization. These embryo models were first developed by the Rivron laboratory from mouse stem cells (Nature, 2018) and then from human stem cells (Nature, 2021). Blastoids provide an ethical alternative to the use of embryos for research and, importantly, enable many discoveries to be made.

Now blastoids have solved the chicken or the egg dilemma. Using mouse blastoids, the researchers found that the early embryonic part (~10 cells) instructs the formation of the future placental part (~100 cells) as well as changes in uterine tissue. “By doing this, the embryo invests in its own future: it contributes to the formation of tissues that will soon take care of its development. The embryo is under control, giving instructions to create a favorable environment,” says Nicolas Rivran.

Indeed, the team discovered several molecules secreted by the few cells from which the fetus develops, the epiblasts. They observed that these molecules tell other cells, the trophoblasts, which later form the placenta, to self-renew and reproduce – two properties of stem cells that are important for the growth of the placenta.

The team also found that these molecules cause trophoblasts to secrete two other molecules, WNT6 and WNT7B. WNT6 and WNT7B tell the uterus to wrap around the blastocyst. “Other researchers have previously seen that WNT molecules are involved in the uterine response. We now show that these signals are WNT6/7B and that they are produced by blastocyst trophoblasts to tell the uterus to respond. The relevance can be high, because we have confirmed that these two molecules are also expressed by trophoblasts of human blastocysts,” says Nicolas Rivron.

The team made their findings in part by examining the degree to which mouse blastoids implanted in an in vivo mouse model of implantation. “I was very surprised at the efficiency with which our blastoids implanted in the uterus. And by changing the properties of trophoblasts inside the blastoids, including the level of WNT6/7B secretion, we could precisely change the size of the uterine cocoon,” he says. co-author Jinwoo Song, a postdoctoral fellow in Rivron’s lab, conducted these experiments.

Because implantation is a bottleneck in human pregnancy — about 50 percent of pregnancies end at this time — and WNT6 and WNT7B are also present in human blastocysts, these findings may explain why things sometimes go wrong. “We are currently repeating these experiments with human blastoids and uterine cells, all in the same dish, to assess the conservation of such basic developmental principles. These discoveries may ultimately contribute to the improvement of IVF procedures, the development of conception drugs and contraceptives,” says Nicolas Rivran. .

The collaboration was also driven by two other co-authors: Javier Frias Aldeguer, a former Ph.D. student, and Victoria Holtzmann, a current Ph.D. a student. “Understanding these fundamental principles of embryonic development will ultimately help empower women to better control their fertility, which will not only improve family planning, but also impact gender equality in society,” says Victoria Holtzman.

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