DNA editing in human embryos reveals role of fertility "master gene"

CRISPR-edited embryo

Niakan's group focused on a gene called OCT4 (also known as POU5F1), a master regulator of gene activity, which is important in mouse embryo development.

Scientists at the Francis Crick Institute, a medical research center, have identified the role of a key gene that controls how embryos form during the first few days of development.

Researchers have used a genome-editing technique to elucidate the role of a gene that is key to human embryonic development. This is basic research which is providing us with a foundation of knowledge about early human development.

Stopping a gene from working and exploring what happens when it's gone is a good way to find out the gene's objective. First, she and her team are eager to better understand exactly how Oct4 is working in the first days of embryo formation, and they want to further explore how it affects placenta development as well, since that's a new role that the CRISPR embryos revealed. They found that roughly 80 percent of the edited embryos didn't develop into blastocysts, the stage when an embryo implants into the womb-usually five to seven days after fertilization. During this time, the blastocyst also begins to form.

OCT4 is a gene that is thought to be required for reprogramming in human cells, but whose function in early human embryos is poorly understood. "We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role", said Norah Fogarty from the Francis Crick Institute. "Pluripotent" stem cells, which can be derived from human embryos, can form any type of tissue in the body and scientists use stem cell technology to create tissue that can fix damage or replace missing structures in the body. "If you do this in mice, you can test hundreds of embryos", he says. The initially frozen embryos were donated by couples who had undergone IVF treatment.

"Now we have demonstrated an efficient way of doing this, we hope that other scientists will use it to find out the roles of other genes".

The team from London's Francis Crick Institute was the first to probe gene function in spare embryos from IVF clinics using the powerful technique.

"It may take many years to achieve such an understanding, our study is just the first step", Niakan said.

Using CRISPR-Cas9, the team were able to change the DNA of 41 human embryos.

Last month Dr Shoukhrat Mitalipov and a team of USA scientists told how they edited human embryos with Crispr/Cas9 to remove a mutant gene linked to heart failure. "What we know about human development is largely inferred from studies of mice, frogs and other model organisms".

The form of research, however, does not come without controversy, as it involved manipulating the genes of human embryos and the potential to alter the germline: how DNA is passed on though generations.

This study was conducted under a research license with strict regulatory oversight from the Human Fertilisation and Embryology Authority (HFEA) - the UK Government's independent regulator overseeing infertility treatment and research.

"Day 5 embryo" (left) shows the embryo on the fifth day of development and "Day 5 edited embryo" shows an edited embryo without OCT4.

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