Saving Sperm Cells 'For Later'

It's a common practice among men preparing to undergo radiation or chemotherapy to have their sperm frozen, as both procedures can render the sperm infertile. But what about boys, who have not yet entered puberty and have no sperm yet to freeze?

Fewer than 1 percent of the nation’s cancer cases involve children, according to the American Cancer Society, which estimated that a little more than 10,000 children under the age of 15 would be diagnosed with cancer last year. More than four out of five survive five years or more, but prepubescent boys risk getting azoospermia, a lack of viable sperm.

For these youngsters, there is a new procedure being developed by Washington State University. The premise is that sperm stem cells be removed from the boys, frozen, and placed back into testes after puberty, at which point they would produce sperm.

Working with prepubescent mice, Jon Oatley, an associate professor in the WSU School of Molecular Biosciences and director of the Center for Reproductive Biology, and his colleagues put a fluorescent tag on a gene specific to stem cells. This let them in effect watch the process of a stem cell differentiating to create the progenitors that eventually become sperm.

They key to success has to do with a process called “glycolysis.” That's one of the ways stem cells create energy. The other way, called oxidative phosphorylation, produces free radicals that can be particularly harmful to a cell’s DNA. Oatley and his team need to convince the sperm stem cells to use glycolysis as exclusively as possible.

“If you’re a stem cell that is going to give rise to sperm essentially through the whole lifetime of an individual, you want to have a pristine genome,” said Oatley. “You don’t want it damaged by reactive oxygen species. That’s why we think glycolysis is important for the stem cell. So we tried to change the culture environment to favor glycolysis.”

The scientists found that by lowering the oxygen in the culture – adding nitrogen to cut it by more than half – they could dramatically improve the percentage of stem cells capable of making normal sperm when put back into the testes. Where before only 5 percent of the cells remained viable after six months, now 40 percent were usable.

Next steps? The researcher intend to see if the cultured stem cells undergo changes to their epigenome, which determines if genes are turned on and off. And of course they also need to investigate whether the technique will work with human tissues.

The research was published in the journal Stem Cell Reports.