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Genes active from one-cell stage of human embryo, University of Cambridge, Bath and US researchers find

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Genes are active in human embryos as early as the one-cell stage, researchers have found.

It had been thought that they were not active until two or three days after fertilisation when an embryo is made of four to eight cells.

Dr Giles Yeo. Picture: Keith Heppell
Dr Giles Yeo. Picture: Keith Heppell

The study, co-led by Dr Giles Yeo at the University of Cambridge, Prof Tony Perry at the University of Bath, and Dr Matthew VerMilyea at Ovation Fertility in the US, used RNA sequencing for the precision analysis of individual human eggs and one-cell embryos.

They made a detailed inventory of RNA transcripts, which are the products of gene activity, which showed that hundreds of genes awaken in human one-cell embryos.

Previous techniques had not been sensitive to spot this.

“This is the first good look at the beginning of a biological process that we all go through – the transit through the one-cell embryo stage," said Prof Perry. “Without genome awakening, development fails, so it's a fundamental step.”

Many genes activated in one-cell embryos switch off at the four-to-eight cell stage.

“It looks as if there is a sort of genetic shift-work in early embryos: the first shift starts soon after fertilisation, in one-cell embryos, and a second shift takes over at the eight-cell stage,” said Prof Perry.

Understanding how the genomes contained in the parental sperm and egg are awakened could lead to a better understanding of disease, inheritance and infertility.

“Although the trigger for activation is thought to come from the egg, it's not known how; now we know which genes are involved, we can locate their addresses and use molecular techniques to find out," said Prof Perry.

Candidates that might trigger gene activation include factors usually associated with cancer, such as some oncogenes.

The researchers speculated that the natural, healthy role of such factors may be to awaken genes in one-cell embryos which, if proved, could provide an avenue to better understand events that initiate cancer.

The work could also lead to a better understanding of acquired traits, such as obesity. Altering gene activation after fertilisation is a possible mechanism by which these traits could be passed on.

Dr Yeo, from the MRC Metabolic Diseases Unit at Cambridge, said: “If true, we should be able to see this altered gene activation signature at the one cell stage.”

In unhealthy one-cell embryos that do not develop, the team found many of the genes fail to activate.

The finding suggests that using abnormal embryos as a method of evaluating methods of human heritable genome editing, as has been done in some research, may not be a reliable method.

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