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Healthy mice created from eggs and sperm without conventional fertilisation

19 September 2016
Appeared in BioNews 869

Unfertilised mouse egg cells that have been made to divide can develop into healthy offspring by the injection of sperm, according to a new study.

The findings challenge scientific understanding of human embryo development and could potentially lead to fertility treatments in the future.

Cell division normally occurs in nature only after an egg cell has been fertilised with a sperm to become an embryo. But eggs can also be chemically treated to 'trick' them into beginning to divide without being fertilised. These so-called 'parthenogenotes' usually die after a few days. As these cells have not joined with sperm, they are haploid, containing only one set of chromosomes.

In the study, published in Nature Communications, scientists took mouse parthenogenotes that were about to divide for the first time and injected them with sperm. They then implanted the parthenogenotes into a female mouse's uterus. The cells developed into normal embryos and went on to grow into newborn mouse pups, up to 24 percent as often as normal embryos would.

The pups appeared to be healthy and were able to produce at least two generations of their own offspring.

'Our work challenges the dogma ... that only an egg cell fertilised with a sperm cell can result in a live mammalian birth,' said Dr Tony Perry of the University of Bath, a lead author on the study.  

Eggs are said to 'remodel' sperm when they transform them from sperm cells into half the genetic material of an embryo, and it had been thought that only egg cells had this ability. Dr Hugh Clarke, a developmental biologist at McGill University in Montreal who was not involved in the study, told The Scientist that it 'shows that eggs that have already begun embryonic development, and are about to divide from the one-cell to two-cell stage, still retain the ability to "remodel" sperm DNA'.

'This is the first time that anyone has been able to demonstrate that embryos can reprogram a differentiated cell of any kind,' said Dr Perry, who suggested that other cell types might also be able to reprogram sperm. If so, he said, 'it might one day mean that we could generate embryos from other cell types – perhaps even somatic cells, perhaps skin cells, for example.'

The researchers noted that the DNA of the mice produced in this way had different epigenetic markers – chemical modifications to the DNA not affecting its sequence – to the pups produced from normal eggs. 'That is, to my mind, really important because it suggests that you can obtain offspring by different epigenetic paths,' said Dr Perry.

Dr Paul Colville-Nash of the Medical Research Council, which funded the study, said: 'This is an exciting piece of research which may help us to understand more about how human life begins and what controls the viability of embryos, mechanisms which may be important in fertility. It may one day even have implications for how we treat infertility, though that's probably still a long way off.'

SOURCES & REFERENCES
Could fertility breakthrough lead to babies with no mothers?
NHS Choices |  15 September 2016
Live Mice Are Bred from Artificially Developed Egg
Live Science |  14 September 2016
Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes
Nature Communications |  13 September 2016
Scientists make mice from non-egg cells
University of Bath News |  13 September 2016
Study: Mitotic Cells Can Reprogram Mouse Sperm
The Scientist |  13 September 2016
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