World's First Monkey Born Using Cryogenically Preserved Testicular Tissue

For the first time, scientists used cryogenically frozen testicular tissue from monkeys to produce functional sperm, which was then used to produce a healthy macaque infant. This experimental method could one day provide a way to preserve fertility in boys treated for cancer—which often results in infertility that lasts into adulthood.

"Some cancer treatments work by killing cells that are dividing rapidly. Since germ cells (sperm cells in the testes and oocytes in the ovaries) divide quickly, they are vulnerable to toxicity, especially from chemotherapy," Lynne Elmore, scientific director at Translational Cancer Research at the American Cancer Society, told Newsweek.

"Permanent infertility can result in males if all the immature cells in the testicles that divide to make new sperm (spermatogonial stem cells) are damaged to the point that they can no longer produce sperm."

For adults, sperm and eggs can be cryopreserved for use at a later date. But for prepubescent children, this is not an option. Instead, ovarian and testicular tissue can be preserved. In girls, tissue can and has been transplanted back into the patient to restore fertility—but there is currently no way to derive sperm from banked tissue.

In previous research, scientists used testicular tissue cryopreservation to produce live offspring of mice and pigs. To move this research forward toward human trials, however, scientists had to show it could be successfully repeated in primates—with healthy offspring produced. Past attempts to do this had failed.

In a study published in Science, a team of researchers from the U.S. and Canada produced the first monkey from cryopreserved testicular tissue.

To do this, they took testicular tissue from castrated mature rhesus macaques. This tissue was then cryopreserved before it was regrafted under the back or scrotal skin. These grafts then grew and went on to produce testosterone and sperm. The sperm was taken from the monkeys and used for insemination via intracytoplasmic sperm injection (ICSI)—in which a single sperm cell was injected directly into the cytoplasm of an egg.

In total, 138 eggs were fertilized by ICSI. Eleven were transferred into six macaque females, and one pregnancy was confirmed in December 2017. The monkey, named Grady, was born in April 2018.

So far, researchers say, Grady's development has been normal. "We continually monitor Grady's health, social interactions and play activities. Her development is similar to other monkeys of the same age," study author Kyle Orwig, from the University of Pittsburgh School of Medicine, told Newsweek. The team said that while more research in monkeys was needed, it hoped to eventually start work on human tissues.

Grady monkey
Grady was born in April 2018 and since then has been developing normally. Oregon National Primate Research Center of the Oregon Health and Science University

"I think this is a very mature technology that is ready for translation to the human clinic," Orwig said. "We want to show that the same approach will work with human tissues."

The study was welcomed by stem cell scientists Nina Neuhaus and Stefan Schlatt, who in an accompanying editorial said it "brings this as yet experimental approach close to clinical application." But they warned that tests on human tissue must be closely monitored to ensure no genetic changes get introduced along the way.

Elmore, who was not involved in the research, also urged caution over the results. She said there were many limitations to the study, and concerns that needed to be addressed—for example, if the cancer patient had leukemia, lymphoma or testicular cancer, the grafting of the cryopreserved testes could reintroduce cancer cells. It was also not clear whether the grafts would produce sperm without the host being castrated, she said.

It was too early to tell whether the findings could lead to human treatment. "While the results of this proof-of-concept study are promising," said Elmore, "there are numerous biological and experimental caveats that make discussions about the prospects of clinical utility far premature."

Grady 2
Grady is the first monkey to be born using sperm derived from cryogenically frozen testicular tissue. Oregon National Primate Research Center of the Oregon Health and Science University
World's First Monkey Born Using Cryogenically Preserved Testicular Tissue | Tech & Science