Making stem cells from fibroblasts combats genetic infertility in mice

While the Crick scientists' method deletes an extra chromosome and leads to the production of mature sperm, it caused tumors to form in some mice, a problem they will have to solve before the treatment can be viable in humans.

Scientists from the Francis Crick Institute used stem cells and assisted reproduction to create healthy offspring from genetically infertile mice. If they can iron out some problems with the technique, it could become a new method to overcome genetic infertility in humans.

Most people are born with two sex chromosomes—girls with two X chromosomes, and boys with an X and a Y chromosome. But approximately 1 in 500 boys are born with an extra sex chromosome, which can interfere with sperm maturation and cause infertility.

The researchers gathered fibroblasts—which produce collagen and other fibers—from the ear tissue of XXY and XYY mice and turned them into stem cells. In the process, some of the cells lost the extra chromosome. The team coaxed these stem cells to become cells with the potential to develop into sperm and then injected them into the testes of the mice. They collected the mature sperm and used assisted reproduction to create healthy, fertile offspring. The research is published in Science.

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The researchers had already found that making stem cells from the fibroblasts of men with Klinefelter syndrome (XXY) gets rid of the extra sex chromosome. But injecting cells back into the mice caused some of them to develop tumors. More research is needed to circumvent this side effect.

"There is currently no way to make mature sperm outside of the body,” said senior author James Turner, in a statement. Reducing the risk of tumor formation, he added, "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."

A range of medical conditions and treatments, as well as environmental factors, can lead to male infertility. Other genetic syndromes linked to infertility include cystic fibrosis, Kallmann syndrome, characterized by delayed or absent puberty, and Kartagener syndrome, which affects the airways and causes a person’s internal organs to be on the opposite side of the body.

Episona launched a physician-ordered infertility test last October, which predicts male factor infertility based on epigenetic marks on DNA. These are methyl groups that bind on top of DNA to control which genes are active and inactive, and can be affected by aging and environmental factors.

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