Reprogramming ‘Fixes’ Trisomic Sperm – Asian Scientist Magazine

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Aug 22 2017

AsianScientist (Aug. 22, 2017) - Scientists have found a way to remove extra sex chromosomes that cause genetic infertility to produce healthy offspring. These findings, published in Science, offer a potential new approach to tackling a common genetic cause of human infertility.

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 1 in 500 boys are born with an extra X or Y, a condition known as trisomy. Men with Klinefelter syndrome have an extra X chromosome (XXY) while men with double Y syndrome are XYY.

In the present study, researchers from Kyoto University, the Japan Science and Technology Agency, the Japan Society for the Promotion of Science and the Francis Crick Institute have found that reprogramming cells from trisomic mice can cause the loss of the extra chromosome. Sperm generated from the resulting corrected induced pluripotent stem (iPS) cells could be used to create healthy, fertile offspring.

Firstly, the team 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, said first author Dr. 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. However, lots more research is needed before this approach could ever be used in humans, the researchers said.

There is currently no way to make mature sperm outside of the body, explained study senior author Dr. James Turner, Group Leader at the Francis Crick Institute.

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.

The article can be found at: Hirota et al. (2017) Fertile Offspring from Sterile Sex Chromosome Trisomic Mice.

Source: Francis Crick Institute; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Reprogramming 'Fixes' Trisomic Sperm - Asian Scientist Magazine

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