In a world first, sperm from a frozen sample of testicle tissue has been used to create a baby monkey, in a study that could have huge implications for young people undergoing treatment for cancer that could affect their fertility.
If replicated in humans, boys undergoing chemotherapy that could affect their ability to produce sperm could have their testicle tissue frozen, preserving it for if and when they want children themselves. Before it can be tested in humans, scientists tested it on monkeys, and a paper published in Science today announced the birth of a healthy baby Rhesus macaque, named Grady.
Importantly, Grady was born from the cryopreserved testicular tissue of a prepubescent macaque, which had not started producing sperm yet.
Adult men can choose to freeze their sperm before undertaking cancer treatment that may damage their fertility. Boys can't produce sperm until they go through puberty, when hormonal changes increase testosterone, which kick-starts stem cells in the testes to start producing sperm. In prepubescent boys, chemotherapy or radiation therapy can kill off those cells, causing permanent infertility.
There are clinics and fertility centers that have already started keeping frozen tissue from testicles before children start cancer treatment, in the hope that one day scientists will successfully find a way to use it to produce viable sperm. Now, with the success of Grady, researchers have shown it can be done – albeit, in primates – but this is a huge step.
“Cancer survivors tell us that their fertility status has a really important impact on their quality of life,” senior author Dr Kyle Orwig, professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine (UPMC), told The Verge. “This advance is an important step toward offering young cancer patients around the world a chance at having a family in the future,” he added in a statement.
More than 300,000 children are diagnosed with cancer around the world each year, nearly 11,000 in the US alone, but cancer survival rates are now more than 80 percent, so the need for this kind of fertility assistance is increasing.
“Previous research in non-human primates has demonstrated that sperm could be produced from autologous transplants of frozen prepubertal testicular tissue, but the ability to produce a healthy live offspring – the gold standard of any reproductive technology – has not been achieved until now,” said first author Adetunji Fayomi.
To do this, researchers from UPMC developed a monkey model of cancer survivorship. Before starting chemo, they removed the testis of a young macaque and cryopreserved the tissue. After chemo, as the monkeys approached puberty, the other testis was removed, and the thawed frozen sample was grafted to the skin of the original monkey, along with transplanted tissue from the just-removed testis. As the monkeys entered puberty, their testosterone levels kicked in, allowing the grafted tissue to mature, and start producing sperm.
A year after the animals went through puberty and began producing sperm, samples were sent to the Oregon National Primate Research Center at Oregon Health and Science University, who were able to produce viable embryos transferred to host females. In April 2018, Grady was born.
“With Grady’s birth, we were able to show proof-of-principle that we can cryopreserve prepubertal testicular tissue, and later use it to restore fertility as an adult,” Fayomi said.
The researchers hope the next step will be a clinical trial, but there are still issues to tackle before that stage. Grady needs to be studied to see how she grows, and if there are any health concerns, and the issue of previous animal test subjects having all been castrated, whereas humans will likely have their testicles intact, needs to be addressed, amongst others. But this is a groundbreaking first step in the right direction.
