The first few weeks after sperm meets egg still hold many mysteries. Among them: what causes the process to fail, leading to many cases of infertility.

Despite the importance of this critical stage, scientists haven’t had a good way to explore what can go wrong, or even what must go right, after the newly formed ball of cells implants in the wall of the human uterus.

But a new achievement using human stem cells may help change that. Tiny lab-grown structures could give researchers a chance to see what they couldn’t before, while avoiding ethical issues associated with studying actual embryos.

A team from the University of Michigan reports in Nature Communications that they have coaxed pluripotent human stem cells to grow on a specially engineered surface into structures that resemble an early aspect of human development called the amniotic sac.

The cells spontaneously developed some of the same structural and molecular features seen in a natural amniotic sac, which is an asymmetric, hollow ball-like structure containing cells that will give rise to a part of the placenta as well as the embryo itself.

But the structures grown at U-M lack other key components of the early embryo, so they can’t develop into a foetus. It’s the first time that a team has grown such a structure starting with stem cells, rather than coaxing a donated embryo to grow, as a few other teams have done.

‘As many as half of all pregnancies end in the first two weeks after fertilisation, often before the woman is even aware she is pregnant. For some couples, there is a chronic inability to get past these critical early developmental steps, but we have not previously had a model that would allow us to explore the reasons why,’ said co-senior author, Deborah Gumucio, Professor of Cell and Developmental Biology and Professor of Internal Medicine

‘We hope this work will make it possible for many scientists to dig deeper into the pathways involved in normal and abnormal development, so we can understand some of the most fascinating biology on earth.’

The researchers have dubbed the new structure a post-implantation amniotic sac embryoid, or PASE. They describe how a PASE develops as a hollow spherical structure with two distinct halves that remain stable even as cells divide.

One half is made of cells that will become amniotic ectoderm; the other half consists of pluripotent epiblast cells that in nature make up the embryonic disc. The hollow centre resembles the amniotic cavity – which in normal development eventually gives rise to the fluid-filled sac that protects and cushions the foetus during development.

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