Scientists have created healthy offspring from genetically sterile male mice carrying an extra chromosome, a new study said Thursday, offering new hope to men who are infertile due to the same genetic problem.
Our sex is determined by the X and Y chromosomes. Usually, girls have two X chromosomes (XX) and boys have one X and one Y (XY), but approximately one in 500 boys are born with an extra X or Y, and having three rather than two sex chromosomes can disrupt formation of mature sperm and cause infertility, according to the new study published in the U.S. journal Science.
Now, scientists at the Francis Crick Institute in Britain found a way to remove the extra sex chromosome to produce fertile offspring.
The team first took small pieces of ear tissue from XXY and XYY mice, cultured them, and collected connective tissue cells known as fibroblasts.
Then, they turned the fibroblasts into stem cells and noticed that in the process, some of the cells lost the extra sex chromosome.
With an existing method, they used specific chemical signals to "guide" the stem cells into becoming cells that have the potential to become sperm.
When injected into the testes of a host mouse, these cells developed into mature sperm, which were then harvested and used to create healthy, fertile offspring through assisted reproduction.
"Our approach allowed us to create offspring from sterile XXY and XYY mice," first author Takayuki Hirota from the Francis Crick Institute, said in a statement.
In a preliminary experiment, the team found that stem cells produced from fibroblasts of men with Klinefelter syndrome (XXY) also lost the extra sex chromosome.
If the findings can be safely transferred into humans, it might eventually be possible for men with Klinefelter syndrome or Double Y syndrome (XYY) that are infertile to have children through assisted reproduction using this technique, the researchers said.
However, more research is needed before this approach could ever be used in human trials.
"There is currently no way to make mature sperm outside of the body," senior author James Turner, group leader at the Francis Crick Institute, explained.
"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," Turner said.
"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," he said.
The research was done in collaboration with Kyoto University and funded by the European Research Council, the Japan Science and Technology Agency, and the Japan Society for the Promotion of Science.
Professor Adam Balen, chairperson of the British Fertility Society, who was not involved in the study, said: "This is fascinating science, but its application for the improvement of fertility in men with Klinefelter's syndrome, which is a relatively common condition, is a long way off clinical practice."
"Furthermore there are possible significant risks outlined in the paper which mean that any therapeutic application is far from certain," Balen said.
