HomeEarly Embryo Drives The Onset Of Life. But How? New Study Reveals

Early Embryo Drives The Onset Of Life. But How? New Study Reveals

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The early embryo is commonly believed to be fragile and in need of care. But in the early stages of development, it has the ability to nourish the developing placenta and provide the uterus instructions so that it can nest.

The Lab of Nicolas Rivron at IMBA demonstrated, using ‘blastoids,’ in vitro embryo models produced from stem cells, that the initial molecular signals that stimulate placental growth and prep the uterus come from the embryo itself.

The results, which have just been published in Cell Stem Cell, might help us comprehend human fertility.

At the very beginning of life, who looks after who and why? The uterus and placenta provide the fetus with care and protection. But until now, it was unknown what was happening at the very beginning of development, when the blastocyst was still floating in the uterus.

A mouse blastoid fluorescently stained for various cellular components. Image 1

Now, utilizing blastoids, Nicolas Rivron’s research team at IMBA (Institute of Molecular Biotechnology of the Austrian Academy of Sciences) has discovered the fundamental concepts underlying early development.

Blastoids are in vitro replicas of the blastocyst, the first few days of a mammalian embryo after conception. The Rivron lab first created these embryo models using mouse stem cells (Nature, 2018), and then using human stem cells (Nature, 2021).

Blastoids offer an ethical alternative to using embryos for study and, more crucially, allow for many discoveries.

A mouse blastoid fluorescently stained for various cellular components. Image 2

Now, blastoids have solved a “chicken or egg” problem. Using mouse blastoids, the researchers discovered that the early embryonic part (~10 cells) tells the future placental part (~100 cells) to form and changes the uterine tissues.

“By doing this, the embryo invests in its own future,” says Nicolas Rivron, and “it promotes the formation of the tissues that will soon take care of its development. The embryo is in control, instructing the creation of a supporting surrounding.”

In fact, the scientists found a number of chemicals produced by the epiblasts, the few cells from which the embryo develops. The trophoblasts that subsequently form the placenta are instructed by these molecules to self-renew and multiply, two stem cell characteristics that are crucial for the placenta to develop.

The team also discovered that the trophoblasts secrete two more molecules, WNT6 and WNT7B, as a result of these molecules. The uterus receives instructions to enclose the blastocyst from WNT6 and WNT7B.

“Other researchers had previously seen that WNT molecules are involved in the uterine reaction. Now we show that,” adds the author, “these signals are WNT6/7B and that they are produced by the blastocyst trophoblasts to notify the uterus to react. The relevance could be high because we have verified that these two molecules are also expressed by the trophoblasts of the human blastocyst.”

An axis of protein expression in a mouse blastoid

The team came to their conclusions by looking at how well the mouse blastoids were implanted in an in vivo implantation mouse model.

“I was very surprised by the efficiency at which our blastoids implanted into the uterus,” says co-first author Jinwoo Seong. “And by changing the properties of the trophoblasts within blastoids, including the secretion levels of WNT6/7B, we could clearly change the size of the uterine cocoon.”

Since WNT6 and WNT7B are also present in human blastocysts, and since implantation is the bottleneck in human pregnancies (about 50% of pregnancies fail at that stage), these discoveries may provide light on why, sometimes, things go wrong.

“We are currently repeating these experiments with human blastoids and uterine cells, all in a dish, to estimate the conservation of such basic principles of development. These discoveries might ultimately contribute to improving IVF procedures, developing fertility drugs, and contraceptives” adds Nicolas Rivron.

Image Credit: ©Rivron/CellStemCell/IMBA

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