Male fertility treatment study

Mice created sperm after they were given implants from rats that had been cryopreserved for almost a quarter of a century. (Credit: University of Pennsylvania)

PHILADELPHIA — Using testicular tissue frozen for decades, scientists say it may be possible to restore fertility in men.

In experiments with mice, the animals successfully created sperm after receiving a tissue implant that had been cryopreserved for almost a quarter of a century. A team from the University of Pennsylvania says the technique could enable young boys undergoing cancer treatments to have children in the future.

Doctors can freeze sperm from adult male patients, but boys do not start producing mature sex cells until they reach puberty. At that point, hormonal changes in the body ramp up testosterone levels, spurring stem cells in the testes to develop into sperm. Chemotherapy and radiation treatments can deplete these stem cells, resulting in low sperm levels and infertility.

“Our study showed that rat spermatogonial stem cells can be successfully frozen for over 20 years, transplanted into an infertile recipient animal and regenerate the ability to produce sperm, albeit at a reduced rate. This could provide a method to recover the loss of fertility in prepubertal boys treated for cancer,” says lead author Dr. Eoin Whelan in a media release.

Study authors add doctors could harvest and freeze testicular tissue for eventual reimplantation before chemotherapy starts.

How long can this tissue survive?

This tissue contains stem cells. Three years ago, a baby macaque monkey was born after short-term freezing of testes tissue. For young boys with cancer, however, reimplantation may not be feasible for a decade or more after harvesting.

It raises the question of how long frozen spermatogenic stem cells (SSCs) can remain viable. The rate of survival for childhood cancers continues to rise, but a serious side-effect of treatment is diminished fertility later in life.

In the first study of its kind, researchers thawed rat SSCs frozen in their laboratory for more than 23 years. They implanted them in infertile mice genetically engineered to lack an immune response that would otherwise reject the foreign tissue.

The long-frozen SSCs had similar profiles of gene expression to those cryopreserved for only a few months. They were able to colonize the mouse testis and generate all of the necessary cell types for successful production of swimming sperm. The SCCs all came from a single rat colony maintained over several decades.

However, they did not generate as many sperm as “younger” counterparts from more recently harvested tissue samples. They compared the ability of the long-frozen SSCs to generate viable sperm to SSCs frozen for only a few months, and to freshly harvested SSCs, all from a single rat colony maintained over several decades.

Still a long way from human trials

The results, published in the journal PLOS Biology, have several important implications.

Study authors point out the importance of in situ testing of SSC viability, instead of relying on biochemical or cellular biomarkers for determining the potential of cryopreserved cells. They add that these methods may not reflect the actual loss of stem cell viability over time.

While there are no protocols that can expand human SSCs for reimplantation at the moment — a requirement for clinical development of this treatment — these protocols may need to consider time-dependent degradation of viability. However, this also depends on how much human SSCs mimic those of rats.

On a positive note, researchers say viability is by no means lost during long-term cryopreservation. This means it may be possible to identify and mitigate the key drivers of loss of viability, in order to improve the reproductive options of boys going through childhood cancer treatment.

South West News Service writer Mark Waghorn contributed to this report.

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