May 17, 2022 – University of Pennsylvania scientists who froze testicular tissue from rats more than 2 decades ago have found the tissue is still viable, marking the final step forward in maintaining fertility for cancer survivors male.
More than 23 years after the tissue was frozen, these rat cells were re-implanted and able to produce viable sperm, researchers report in a new PLOS Biology paper.
“This is the first time tissue like this has been frozen for such a long time and used to regenerate whole tissue,” says study lead author Eoin Whelan, PhD, of the Brinster Laboratory of Reproductive Physiology. from the University of Pennsylvania. School of Veterinary Medicine Medicine. “This has implications for a number of areas, including our goal, which is the restoration of fertility for children who have undergone chemotherapy or ablative cell therapy.”
A side effect of these cancer treatments is a decline in fertility later in life, the researchers note. While adolescent boys may have a sperm bank, prepubescent boys, who are not yet producing sperm, have no options for preserving their fertility.
The frozen samples in the study were spermatogenic stem cells, or SSCs — cells in the testicles that produce sperm later in life, Whelan says. Previous research has shown that these cells can remain viable after short-term freezing.
But whether the cells could last for decades, because when a child is big and ready to start a family, remains an open question – until now, of course.
From rats to mice
Cryopreserved in 1996, the rat cells were thawed and implanted into “nude” mice, which lack an immune response that would otherwise reject the foreign tissue. Transplanting rat cells into mice allowed the researchers to distinguish between donor and host in their analysis, Whelan says.
They compared the 23-year-old cells to cells frozen for just a few months. The long-frozen cells were able to grow and multiply in mouse testes and generate the cells needed for sperm production, but not as strongly as samples harvested more recently.
Older cells made fewer “elongated spermatids,” which form free-swimming sperm. And they only produced about a third of the younger sample’s sperm, Whelan notes.
“Because of that, we’re probably not talking about being able to get natural fertility back right now,” he says. “But keep in mind that all you need is good sperm for fertilization. So even if the number is much lower, there is still a chance of successful fertilization.”
From mice to men
Although testicular tissue banking is a promising way to protect fertility, it needs to be tested in humans first. Whelan thinks human clinical trials could begin within the next few years.
In the meantime, clinics are offering to cryopreserve testicular tissue from prepubescent boys facing cancer treatment in hopes the technology will one day allow them to restore their fertility, Whelan says. But time is running out for these samples.
“It’s not like we can keep waiting 20 years between trial periods,” Whelan says. “But this is promising for people with childhood cancers, that they may have more fertility in the future than they thought.”
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