September 13, 2016

Baby mice made from non-egg cells and could lead to babies using cells not from eggs

Researchers have succeeded in creating healthy baby mice by tricking sperm into believing they were fertilising normal eggs.

The University of Bath scientists started with an unfertilised egg in their experiments.

They used chemicals to trick it into becoming a pseudo-embryo.

These "fake" embryos share much in common with ordinary cells, such as skin cells, in the way they divide and control their DNA.

The researchers reasoned that if injecting sperm into mouse pseudo-embryos could produce healthy babies, then it might one day be possible to achieve a similar result in humans using cells that are not from eggs.

University of Bath have developed a method of injecting mouse parthenogenotes with sperm that allows them to become healthy baby mice with a success rate of up to 24 per cent.
This compares to a rate of zero per cent for parthenogenotes or about two per cent for nuclear transfer cloning.

Mice born by this method appear healthy and are able to produce at least two generations of offspring

Scientists at Bath have developed a method of injecting sperm into a one cell mouse embryo, which can go on to produce offspring

Nature Communications - Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes

Sperm are highly differentiated and the activities that reprogram them for embryonic development during fertilization have historically been considered unique to the oocyte. We here challenge this view and demonstrate that mouse embryos in the mitotic cell cycle can also directly reprogram sperm for full-term development. Developmentally incompetent haploid embryos (parthenogenotes) injected with sperm developed to produce healthy offspring at up to 24% of control rates, depending when in the embryonic cell cycle injection took place. This implies that most of the first embryonic cell cycle can be bypassed in sperm genome reprogramming for full development. Remodelling of histones and genomic 5′-methylcytosine and 5′-hydroxymethylcytosine following embryo injection were distinct from remodelling in fertilization and the resulting 2-cell embryos consistently possessed abnormal transcriptomes. These studies demonstrate plasticity in the reprogramming of terminally differentiated sperm nuclei and suggest that different epigenetic pathways or kinetics can establish totipotency.

“It had been thought that only an egg cell was capable of reprogramming sperm to allow embryonic development to take place.

“Our work challenges the dogma, held since early embryologists first observed mammalian eggs around 1827 and observed fertilisation 50 years later, that only an egg cell fertilised with a sperm cell can result in a live mammalian birth.”

The idea was the brain child of Dr Toru Suzuki in Dr Perry’s team in the University of Bath’s Laboratory of Mammalian Molecular Embryology, who performed the study together with team member Dr Maki Asami and colleagues from the University of Regensburg and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

The baby mice born as a result of the technique seem completely healthy, but their DNA started out with different epigenetic marks compared with normal fertilisation. This suggests that different epigenetic pathways can lead to the same developmental destination, something not previously shown.

Making embryos from non-egg cells

The discovery has ethical implications for recent suggestions that human parthenogenotes could be used as a source of embryonic stem cells because they were considered inviable. It also hints that in the long-term future it could be possible to breed animals using non-egg cells and sperm. Although this is still only an idea, it could have potential future applications in human fertility treatment and for breeding endangered species.

SOURCES - University of Bath, Nature Communications

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