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Sperm from stem cells could help some types of male infertility

21 August 2017
Appeared in BioNews 914

Cells from genetically infertile male mice have been turned into sperm, and used to produce healthy pups.

Researchers hope the technique could one day help men with certain causes of infertility. Experts hailed the work as 'very encouraging' and 'fascinating science', while noting that the technique is experimental only, and raises ethical and legal considerations should it be developed for humans.

'Our approach allowed us to create offspring from sterile XXY and XYY mice,' says first author Dr Takayuki Hirota at the Francis Crick Institute in London. 'It would be interesting to see whether the same approach could one day be used as a fertility treatment for men with three sex chromosomes.'

Having an extra sex chromosome – three instead of two – can cause infertility in mice and men. In humans, about one in 500 men may have either an extra X chromosome (Klinefelter's syndrome) or an extra Y chromosome (Double Y) in their genomes.

British and Japanese researchers aimed to remove the extra sex chromosome in infertile male mice with this problem. They took cells from the ears of the mice and cultured them in the lab to collect fibroblast (connective tissue) cells. They then coaxed the fibroblast cells into iPS, induced pluripotent stem cells – in the process some of the cells lost their extra sex chromosome.

Using specific chemical signals, the researchers could guide these stem cells into becoming the cells which can develop into sperm. When these were transplanted into the testes of live mice, they matured into sperm, which were used in assisted reproduction to give healthy pups.

Others agree the study offers potential. 'Although a mouse study, this research is exciting, since it raises the future possibility that sperm without the extra X chromosome could be made,' said Dr Channa Jayasena, a reproductive endocrinologist at Imperial College London. 'This could offer potential hope for affected couples.'

Indeed, a preliminary experiment by the researchers turning fibroblast cells from men with Klinefelter's syndrome into stem cells in vitro managed to lose the extra X chromosome.

But, Dr Jayasena notes the new study 'raises important ethical issues'.

Professor Allan Pacey at the University of Sheffield, UK, said: 'This is very encouraging. The only fly in the ointment is that currently the use of such sperm in the UK is not lawful and it would take a change of primary legislation to allow us to use such sperm in infertility treatment.'

While praising the study, Professor Adam Balen, chair of the British Fertility Society, said its application in improving fertility in men with Klinefelter’s syndrome 'is a long way off clinical practice'.

He also noted: 'Furthermore there are possible significant risks outlined in the paper which mean that any therapeutic application is far from certain.'

The study, published in Science, found that when the cells were transplanted into the testes of mice, some of the animals developed teratomas.

Fertile offspring from sterile sex chromosome trisomic mice (paper)
Science |  17 August 2017
New sperm creation method could overcome genetic male infertility – study
The Guardian |  17 August 2017
New technique overcomes genetic cause of infertility
Francis Crick Institute |  17 August 2017
Scientists may have found a way to overcome common genetic causes of male infertility
The Conversation |  17 August 2017
Stem cell technique could reverse a major type of infertility
New Scientist |  17 August 2017
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