A genetically manipulated mouse pup born from an unfertilised egg survived to adulthood and reproduced, demonstrating a type of reproduction that was thought to be impossible in mammals.
In many plants and some animals, offspring can develop from unfertilised eggs or ovules in a process called parthenogenesis.
In normal sexual reproduction in animals, an egg and a sperm – each containing one set of genetic material – fuse, giving the embryo two copies of each gene. To avoid conflicts between two versions of the same gene, certain genes are switched off in either the maternal or paternal-derived DNA, in a process called imprinting.
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To make an unfertilised egg develop into an embryo, it needs to have two sets of DNA from its mother. This means the pattern of imprinting is the same on both sets, so some genes either clash or fail to activate altogether.
Yanchang Wei at Shanghai Jiao Tong University in China and his colleagues created unfertilised mouse eggs with double the normal number of chromosomes, by adding back in DNA that is ejected in the early stages of egg development.
Then they used the gene-editing tool CRISPR to target seven imprinted gene regions previously identified as important in embryo development, and to change the so-called epigenetic marks, which turn genes on or off. This made the second copy of the mother’s genetic code appear as if it were male, “tricking” the egg into developing into an embryo. The researchers didn’t respond to requests for comment for this article.
“It’s going to turn out to be an important piece of the jigsaw about the mechanism of very early embryo development and the way that the two parental genomes are regulated,” says at the University of Bath, UK. “And secondly, it’s an important technical demonstration of the kind of potency of these [CRISPR tools].”
In 2004, another team fused two unfertilised mouse eggs at different stages of maturity and targeted a couple of imprinting regions, which also led to the birth and development of a mouse. But unlike the efforts by Wei and his team, that wasn’t true parthenogenesis as the embryo was derived from two different egg cells that were combined, says Perry.
Wei and his team edited 227 unfertilised eggs, or oocytes, resulting in 192 embryos. Only 14 of these embryos were carried to term, of which three resulted in live pups. There was just a single mouse that survived to adulthood.
The live pups were underweight compared with normal mouse pups, and displayed certain genetic abnormalities. This suggests that there are still imprinting regions involved in embryo development that we don’t fully understand, says Perry. Another possibility is that the gene editing didn’t work as completely as it should have.
“There is a possibility that some of them may not acquire the right epigenetic mark even after using CRISPR,” says at the University of Cambridge. “It would depend, to some extent, how this editing works and how efficiently it works.”
Perry says it is unlikely that this method could be used to develop human embryos in this way any time soon. “The state of knowledge about imprinted genes in humans is much less [than in mice],” he says. “We can’t do experiments on them in the same way that we can in mice.” Last year, Perry and his colleagues discovered 71 new imprinted genes in about.
However, even one pup surviving to adulthood through targeting imprinted genes represents a significant advance. “The bottom line is that imprinting does remain a very major barrier to parthogenesis,” says Surani. “And they can overcome it by altering the epigenome using CRISPR.”
In 2019, researchers developed mouse fetuses from no egg or sperm at all, instead using stem cells to develop into the embryos from scratch.
PNAS
