Insight into early embryos could explain why some pregnancies fail

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In the early stages of development, the human embryo forms a hollow ball of cells called a blastocyst

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Scientists have identified key molecular events in the earliest stages of human embryo development that could help shed light on why many pregnancies fail.

These events occur in the second week of gestation – between seven and 14 days after fertilisation – in one of the most critical processes of development.

During this period, the embryo acquires a head end and a tail end, the first step in the formation of the overall body pattern in humans.

Magdalena Zernicka-Goetz at the University of Cambridge and her team have found that this process is initiated by a group of cells outside the embryo, in a tissue known as the hypoblast. They say that the findings could help us understand more about why early pregnancy loss occurs.

“Our goal has always been to enable insights to very early human embryo development in a dish, to understand how our lives start,” says Magdalena Zernicka-Goetz.

“By combining our new technology with advanced sequencing methods, we have delved deeper into the key changes that take place at this incredible stage of human development, when so many pregnancies unfortunately fail.”

At present, very little is known about the development of the human embryo once it implants in the uterus, due to ethical restrictions on the use of human embryos in research.

In 2016, Zernicka-Goetz and her team developed a technique to culture human embryos outside the body, allowing them to be studied up to day 14 of development, in line with UK ethical guidance.

As part of the new study, the team collaborated with colleagues at the Wellcome Sanger Institute in the UK to find out what happens at the molecular level during this early stage of human embryo development.

They found that the hypoblast sends a message to the embryo that kick-starts the development of the head-to-tail body axis, where one end becomes committed to developing into the head end, and the other the tail.

“We have revealed the patterns of gene expression in the developing embryo just after it implants in the womb, which reflect the multiple conversations going on between different cell types as the embryo develops through these early stages,” says Zernicka-Goetz.

“We were looking for the gene conversation that will allow the head to start developing in the embryo, and found that it was initiated by cells in the hypoblast, a disc of cells outside the embryo,” she says. “They send the message to adjoining embryo cells, which respond by saying, ‘OK, now we’ll set ourselves aside to develop into the head end’.”

Journal reference: Nature Communications, DOI: 10.1038/s41467-021-23758-w

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