Study: Male fertility could be restored using frozen tissue

By Mark Waghorn via SWNS

Male fertility could be restored using tissue that has been frozen for decades, according to new research.

Mice created sperm after they were given implants from rats that had been cryopreserved for almost a quarter of a century.

The technique could enable pre-pubescent boys undergoing cancer treatments to have children in the future, say scientists.

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.

Lead author Dr. Eoin Whelan, of the University of Pennsylvania, said: "Our study showed 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 pre-pubertal boys treated for cancer."

He added: "Chemotherapy may be preceded by harvesting and freezing of testicular tissue for eventual reimplantation."

It contains stem cells. Three years ago a baby macaque monkey was born after short-term freezing of testes tissue.

But for young boys with cancer, 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 has soared, but a serious side effect of treatment is diminished fertility later in life.

In the first study of its kind a US team thawed rat SSCs that had been 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 cryo-preserved for only a few months.

They were able to colonise 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.

But 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.

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

Dr. Whelan said: "First, they point out the importance of in situ testing of SSC viability, rather than relying on biochemical or cellular biomarkers, in determining the potential of cryopreserved cells, which may not reflect the actual loss of stem cell potential over time.

"Second, while there currently are no protocols that can expand human SSCs for reimplantation - a requirement for clinical development of this treatment - such protocols may need to consider time-dependent degradation of viability, assuming human SSCs mimic those of rats."

He added: "Finally, and this is the good news, viability is by no means lost during long-term cryo-preservation, suggesting that it may be possible to identify and mitigate the key drivers of loss of viability, in order to improve the reproductive options of boys whose childhood cancers are successfully treated."

With the increasing cure rate of pediatric cancers, infertility has become an important concern for patients and their families, said the researchers.