Scientists turn skin cells of infertile men into sperm precursors

U.S. researchers said Thursday they have successfully coaxed stem cells made from the skin cells of infertile men into producing the precursors of sperm cells. In a study published in the U.S. journal Cell Reports, the researchers said they took skin cells from infertile men and converted them into the so-called induced pluripotent stem cells ( iPSCs), which theoretically have the ability to generate all cell types found in the body. When these iPSC were transplanted into the testes of mice, they developed into sperm precursors. "Our results are the first to offer an experimental model to study sperm development," said Renee Reijo Pera of the Institute for Stem Cell Biology and Regenerative Medicine and Montana State University. "Therefore, there is potential for applications to cell-based therapies in the clinic, for example, for the generation of higher quality and numbers of sperm in a dish." Reijo Pera said it might even be possible to transplant stem- cell-derived germ cells directly into the testes of men with problems producing sperm but more studies are needed to ensure the safety and practicality. Infertility affects 10 percent to 15 percent of couples. Moreover, genetic causes of infertility are surprisingly prevalent among men, most commonly due to the spontaneous loss of key genes on the Y sex chromosome. But the causes at the molecular level have not been well understood. In the new study, the researchers looked to infertile but otherwise normal men with deletions encompassing three Y chromosome azoospermia factor (AZF) regions, which are associated with the production of few or no sperm. They found that iPSCs derived from AZF-deleted cells were compromised in their ability to form sperm in a dish. But when those cells were transplanted into the seminiferous tubules of mice, they produced germ-cell-like cells, though significantly fewer than iPSCs derived from people without the AZF deletion do. The findings may yield new strategies in the diagnosis and assistance of those with genetic or secondary infertility, Reijo Pera said. "Our studies suggest that the use of stem cells can serve as a starting material for diagnosing germ cell defects and potentially generating germ cells," she said. "This approach has great potential for treatment of individuals who have genetic/idiopathic causes for sperm loss or for cancer survivors who have lost sperm production due to gonadotoxic treatments."