Rat testicle cells make sperm after being frozen for 23 years

Pre-pubescent children who become infertile because of cancer treatment may be able to make sperm after reimplanting frozen testicular tissue, if animal research translates to humans

By Clare Wilson

Rat testicle cells that were frozen for 23 years have produced sperm after being implanted into mice.

The findings suggest that children who have testicle tissue frozen before cancer treatment may be able to have the tissue reimplanted so they can one day have their own biological children through in vitro fertilisation (IVF), says Eoin Whelan at the University of Pennsylvania in Philadelphia.

Chemotherapy to treat cancer can kill stem cells in the testicles that make sperm. Adults can have sperm samples frozen before this treatment, but that isn’t an option for children who are yet to go through puberty.

In such cases, some clinics have been removing and freezing small samples of children’s immature testicle tissue in the hope that, if reimplanted when they are adults, it will mature and start making sperm. At least one clinic, located in Belgium, has been approved to start such reimplantation surgery.

Whelan and his colleagues’ study gives some cause for optimism. They took advantage of stem cells from rats that had been isolated and frozen 23 years earlier, thawing and implanting them into the testes of mice.

The mice had been treated with a drug that killed their own sperm-making cells – which is too toxic to use on rats – and had defective immune systems so they couldn’t reject the transplant. For comparison, the same procedure was also done in other mice using rat cells that had been removed and immediately implanted, as well as with rat cells that had been frozen a few months ago.

When the mice’s testes were examined, the 23-year-old stem cells had survived and developed into groups of sperm-producing cells, although they made about 20-fold fewer groups of cells than the fresh tissue or recently frozen tissue. The groups of cells from the 23-year-old implants were making mature sperm, but each one made about a third as many as the ones derived from implants of fresh or recently frozen cells.

Nevertheless, if the same results happen in people, participants could produce some sperm even if numbers are low, says Whelan. “You really only need one viable sperm to succeed.”

It is unclear if the results will translate to people, as there are some differences between the team’s methods and those currently used by fertility clinics, says Rod Mitchell at the University of Edinburgh, UK.

The researchers froze isolated testicle stem cells, while clinics are freezing whole tissue samples. They also took the cells from adult rats, while clinics have to take tissue from children who haven’t yet gone through puberty. “There are a lot of unknowns,” says Mitchell.

Journal reference: PLoS Biology, DOI: 10.1371/journal.pbio.3001618

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