A one-of-a-kind rhesus macaque named Grady is growing up under intense scrutiny at the Oregon National Primate Research Center in Beaverton. That’s because she has an unusual pedigree: researchers created her using sperm from tissue harvested from her father’s testicles when he was young, and then grafted onto his body as an adult. If all goes well with Grady, the technique might one day be used to restore fertility in boys who have received damaging cancer treatments.
Grady’s birth, reported on 21 March in Science1, marks a crucial success in the long-running effort to provide the possibility of fatherhood to boys who are treated for cancer before they are old enough to make sperm that could be frozen and stored for future use. The reproductive biologists who developed the method are now watching the nearly year-old macaque (Macaca mulatta) closely to see whether she develops normally.
Researchers have previously used the technique to produce babies in mice and pigs, says lead study author and reproductive biologist Kyle Orwig at the University of Pittsburgh School of Medicine in Pennsylvania. If Grady grows up without any issues, then the method could be ready for testing in people, he adds.
Transplanting for the future
Orwig’s team harvested tissue from the testicles of five monkeys — including Grady’s father — when they were too young to produce sperm. They froze the tissue samples until just before the monkeys reached puberty, then thawed the samples and sewed the tissue under the skin on the back and scrotum of the animals.
Less than a year later, the patches of tissue were producing testosterone, and all of the tissue recovered from both graft sites were making sperm. Orwig’s team then took sperm from Grady’s father and used in vitro fertilization to produce an embryo.
Other research teams are working to apply similar methods to farm animals by transplanting sperm-producing stem cells from ‘elite’ livestock into less-elite individuals. The hope is that sufficient numbers of sperm from the elite fathers would be produced in the ejaculate of lower-value males. This could speed up breeding efforts by generating many males that are capable of producing high-value offspring.
In 2012, Orwig’s team reported early success using a similar stem-cell transplant technique in monkeys2. But the researchers didn’t produce babies using the sperm at that time, because they couldn’t determine whether any baby monkeys created with this method would have come from sperm made by the transplanted cells, or by cells in the male monkeys that had recovered some function after being damaged.
Still, the success was enough to convince Orwig that a human treatment might be only a decade or two away, and so he launched an effort to collect testicular tissue from boys undergoing fertility-destroying medical treatments. Orwig’s team, along with collaborators at other medical centres, have collected such tissue from more than 200 boys. That tissue could be used for either of Orwig’s approaches — the stem-cell transplants or the tissue grafts described in the latest report — if he can get them to work in people.
One giant leap
For reproductive biologist Stefan Schlatt of the University of Münster in Germany, Orwig’s success with grafting should be enough to pave the way for clinical trials. “I think with that paper, ethics committees throughout the world will be granting clinical studies,” he says.
But Ellen Goossens, a reproductive biologist at Vrije Universiteit Brussel, cautions that tissue transplants from people with cancer could carry malignant cells that are capable of seeding fresh tumours. Researchers will need to develop ways to ensure the grafts are cancer-free, she says.
Nevertheless, the success in monkeys is important for the field, Goossens says. Previous efforts had succeeded in generating sperm when tissue was grafted into rodents, she notes, but sperm production is different between rodents and primates such as monkeys and humans. “It’s a huge step that this can be performed in primates,” she says.