Stem Cell Study Uncovers Clues; Potential Solutions to Male Infertility

One out of every 100 men are unable to produce sperm—making it impossible for them to become biological fathers.

Researchers have long wondered whether this infertility is hardwired from birth. But in new research published this week, scientists have found that this may not be the case. In the latest issue of the journal Cell Reports, scientists report that stem cells made from the skin cells of an infertile adult can yield so-called ‘primordial germ cells,’ the cells that give rise to human sperm. These findings provide new insight into the earliest stages of human reproduction, while also offering hope for the millions of men who today are unable to father their own children.

The research team was led by Renee Reijo Pera, former director of the Stanford University School of Medicine’s Center for Human Embryonic Stem Cell Research and Education (now at Montana State University). Reijo Pera has long looked to regenerative medicine to understand the ins-and-outs of human fertility and reproduction. In fact, Reijo Pera has received CIRM support for her previous studies on the subject, as she summarizes in this 2010 “Spotlight on Disease.”

In this study, Reijo Pera and her team collected skin samples from five men—three of whom had a type of genetic infertility called azoospermia, and two who did not.

Using iPS cell technology, the team transformed those skin cells into embryonic-like stem cells that were genetically identical to the original samples. They then coaxed those cells into becoming germ-line cells—the class of cells that give rise to sperm. Finally, the team implanted these germ-line cells into the reproductive systems of mice to see what would happen next.

To their surprise, the team found that the infertile men’s cells did give rise to germ cells, something entirely unexpected. Reijo Pera describes their initial observations in a recent news release:

“We saw better germ-cell differentiation…than we’ve ever seen. We were amazed by the efficiency.”

However, while the stem cells from the infertile men did produce some germ-line cells, they were up to 100 times less efficient at doing so, when compared to the cells from the fertile men. Understanding the underlying causes of this difference is next on Reijo Pera’s to-do list.

“Studying why this is this case will help us understand where the problems are for these men and hopefully find ways to overcome them.”

The implications of this initial study are far-reaching. First, they suggest that these infertile men may have had at one time some functioning germ cells, perhaps as infants. Reijo Pera and her team hypothesize that collecting and freezing some of this tissue from babies with this type of genetic infertility may give them the opportunity to have their own children.

Michael Eisenberg, who directs the male reproductive medicine and surgery program at Stanford University, was also optimistic. As he stated in the same news release:

“This research provides an exciting and important step for the promise of stem cell therapy in the treatment of azoospermia. While this study clearly demonstrates the importance that genetics play in spermatogenesis [the production of sperm], it also suggests that some of these barriers could potentially be overcome.”

Anne Holden

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