The beginning of life: The early embryo is in the driver’s seat

One often thinks that the early embryo is fragile and needs support. However, at the earliest stages of development, it has the power to feed the future placenta and instructs the uterus so that it can nest. The Lab of Nicolas Rivron at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) 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, could contribute to a better understanding of human fertility.

Who takes care of whom at the onset of life? The placenta and the uterus nurture and shelter the fetus. But the situation at the very early stage of development, when the blastocyst still floats in the uterus, was unclear so far. Now, Rivron’s research group has uncovered basic principles of early development using blastoids.

Blastoids are in vitro models of the blastocyst, the mammalian embryo in the first few days following fertilization. Using mouse blastoids, the researchers found that the early embryonic part (about 10 cells) instructs the future placental part (about100 cells) to form, and the uterine tissues to change. “By doing this, the embryo invests in its own future: 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,” Rivron said.

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 that later form the placenta, to self-renew and proliferate, two stem cell properties that are essential for the placenta to grow.

Because implantation is the bottleneck in human pregnancies — around 50 percent of pregnancies fail at that time — these findings might explain 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,” Rivron said.

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