It is common knowledge that our sex is determined by the X and Y chromosomes; for most parts, the girls have two X chromosomes and the boys, XY chromosomes. But approximately 1 in 500 boys are born with an extra sex chromosome, which can interfere with sperm maturation and cause infertility.
Now, this common genetic cause of male infertility has been overcome in mice using a technique that creates healthy sperm in the laboratory, scientists at the London’s Francis Crick Institute, working with Japanese colleagues, have shown.
In this study, the scientists took small pieces of ear tissue from XXY and XYY mice, cultured them, and collected connective tissue cells known as fibroblasts. 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. These cells developed into mature sperm when injected into the testes of a host mouse. The researchers then harvested these mature sperm and used them through assisted reproduction to create healthy, fertile offspring.
“Our approach allowed us to create offspring from sterile XXY and XYY mice,”
says first author Takayuki Hirota from the Francis Crick Institute. “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.”In a preliminary experiment, the team found that stem cells produced from fibroblasts of men with Klinefelter syndrome 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 (XXY) or Double Y syndrome (XYY) that are infertile to have children through assisted reproduction using this technique.
There are a number of substantial challenges to overcome for this to be realised in humans. The toughest one will be to produce functional germ cells outside the human body. Although we are undoubtedly far from achieving this, but truly breath-taking progress is being made in the area of stem cell and germ cell biology. Coupled with a highly efficient reproductive medicine scene and permissive regulations, we are well placed to address the challenges of translating this exciting research into humans.
