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Functional mouse eggs made from artificial stem cells

24 October 2016
Appeared in BioNews 874

Scientists in Japan are the first to have created live mouse pups from eggs that were made from stem cells.

It is the first time that the entire process of egg development has been recreated in vitro. If the technique could be applied to humans, it could be used to treat female infertility – for older women and those whose ovaries have been damaged by cancer treatment.

'From a technical point of view it could work,' said study lead author Dr Katsuhiko Hayashi from Kyushu University. 'If we could make human eggs, it could be a very powerful tool for curing infertility.'

The study, which was published in Nature, describes how the researchers first created immature eggs by reprogramming two different types of stem cells: embryonic stem cells and induced pluripotent stem cells (iPS cells), which were produced by transforming skin cells from the tails of female mice.

The immature eggs were then matured in a dish before being fertilised using IVF and transferred into female mice. The procedure created 4048 mature eggs, from which 1348 embryos were made. Eventually, 11 healthy pups were born, eight of which were from the skin-derived iPS cells.

The study builds on previous research in which Dr Hayashi and colleagues created immature mouse eggs from iPS cells. However, those eggs needed to fully mature within the ovaries of living mice.

In the new study, immature eggs were cultured in a dish alongside ovarian cells taken from mouse fetuses, which encouraged them to mature. Dr Hayashi's team are now trying to develop an artificial reagent that could replace the ovarian tissue in the protocol.

Although promising, the process is currently very inefficient and has a very high failure rate. Just 3.5 percent of embryos created from in vitro matured artificial eggs led to live births, compared with 62 percent of embryos created from eggs matured inside the mouse. The artificially created eggs also had unusual patterns of gene expression, suggesting that the resulting pups may have developmental abnormalities, even though they appeared healthy and were fertile.

Dr Hayashi next intends to attempt this process in a non-human primate, which will be much more complicated. If the same procedure is eventually be replicated in humans, it could potentially be used to make artificial eggs from male skin cells, raising the possibility of creating babies with two genetic fathers. However, so far Dr Hayashi's team have not been successful when using male skin cells.

The technology also raises many ethical questions that will need to be discussed. Professor Azim Surani, a stem cell scientist at the Gurdon Institute of the University of Cambridge, who was not involved in the study, said: 'This is the right time to involve the wider public in these discussions, long before and in case the procedure becomes feasible in humans.'

Eggs made from skin cells in lab could herald end of infertility
New Scientist |  17 October 2016
Healthy Baby Mice Produced from Mouse Mom's Skin Cells
Scientific American |  17 October 2016
Healthy mice born from first lab-grown eggs spark calls for debate on future use
The Guardian |  17 October 2016
Mouse eggs made from skin cells in a dish
Nature News |  17 October 2016
Reconstitution in vitro of the entire cycle of the mouse female germline
Nature |  17 October 2016
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