PUBLIC RELEASE DATE:

1-May-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

Researchers reporting in the Cell Press journal Cell Reports on May 1st have successfully coaxed stem cells made from the skin cells of infertile men into producing sperm cell precursors. These induced pluripotent stem cells (iPSCs) produced sperm precursors following transplantation into the testes of mice.

The findings help to explain a genetic cause of male infertility and offer a window into basic sperm biology. The approach also holds considerable potential for clinical application, the researchers say.

"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 & 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.

"It might even be possible to transplant stem-cell-derived germ cells directly into the testes of men with problems producing sperm," she added. However, getting to that point will require considerable study to ensure the safety and practicality.

Infertility affects 10% to 15% of couples. Moreover, as the researchers note, 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.

Reijo Pera said her primary motivation is to understand the fundamental decision early in development that enables the production of sperm cell precursors and ultimately sperm. One way to do that is to study cells lacking genes that are required for sperm production.

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).

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Sperm precursors made from stem cells of infertile men