New Sperm Creation Method Could Overcome Genetic Male Infertility – Study

A common genetic cause of male infertility has been overcome in mice using a technique that creates healthy sperm in the laboratory, scientists have shown.

The research raises the future prospect of hope for men who cannot father children because they have three instead of two sex chromosomes.

But such a treatment, even if shown to be safe, would not be allowed in the UK without a change in the law that bans the use of artificially produced sperm to make babies.

An estimated one in 500 boys are born with an extra X or Y sex chromosome that can disrupt the formation of mature sperm, leading to infertility.

Scientists at London’s Francis Crick Institute, working with Japanese colleagues, used a stem cell technique to produce sperm from small pieces of connective tissue taken from the ears of infertile male mice.

The mice either had an extra female X or male Y chromosome in addition to the usual XX or XY pairing.

During the process of transforming the fibroblast connective tissue cells into multi-purpose stem cells, some of the unwanted extra chromosomes were lost.

The researchers selected those stem cells lacking the extra chromosome and used chemical signals to coax their development into immature sperm cells.

Once injected into the testes of a host mouse, the cells matured to become healthy and properly functioning sperm. These were then used to fertilise eggs and produce healthy, fertile offspring.

Lead scientist Dr Takayuki Hirota, of the Francis Crick Institute, said: “Our approach allowed us to create offspring from sterile XXY and XYY mice.

“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.”

The researchers have already taken a first step towards human treatment by conducting preliminary experiments involving men with a three-chromosome infertility condition called Klinefelter syndrome.

Repeating the results seen in mice, they proved it was possible to produce stem cells from the men’s fibroblasts that do not have the extra sex chromosome. In theory, it should be possible to turn these cells into fertile sperm.

The team, whose work appears in the journal Science, stressed the technique was not yet safe and needed much further development before it could be considered as a way of tackling male infertility.

Some of the mice injected with the laboratory-made immature sperm cells developed tumours. Currently, there is no way to produce mature sperm outside the body.

Francis Crick Institute group leader Dr James Turner said: “In our mouse experiments we have to inject cells that have the potential to become sperm back into the testes to help them finish developing.



“But we found that this caused tumours in some of the mouse recipients. So reducing the risk of tumour formation or discovering a way to produce mature sperm in a test tube will have to be developed before we can even consider this in humans.”


Commenting on the findings, leading fertility expert Professor Allan Pacey, from the University of Sheffield, said: “The study … gives a further example about a potential application of lab-derived sperm to help another group of infertile men.

“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.”

Professor Simon Fishel, founder and president of leading IVF treatment providers Care Fertility, said:
“The implications for human fertility are evident in theory but many years of research are necessary to understand if the complex processes involved could ever be regarded as safe for a medical therapy.”


Source: theguardian