AsianScientist (Sep. 30, 2015) – Live and apparently healthy monkeys have been born from sperm derived from xenografts grown on the backs of mice. These results, published in Cell Research, could eventually lead to new techniques of preserving the fertility of cancer patients undergoing radiotherapy or chemotherapy.
Although non-human primates (NHP) reflect human biology more closely than other animal models, their long reproductive cycles (typically 4-5 years) present an obstacle to the widespread use of gene-modified monkeys in research. In an attempt to accelerate the maturation of the testes and facilitate the study of spermatogenesis, several research groups have grafted NHP testis tissue onto nude mice and successfully obtained mature sperm. However, no live births of monkeys derived from such xenografted sperm have been reported until now.
In the present study, Professor Sun Qiang and his team from the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, have successfully generated six healthy cynomolgus monkeys (Macaca fascicularis) from xenograft-derived sperm.
Using two juvenile monkey donors—one expressing GFP and one wild type control—Sun and his team grafted small pieces of testicular tissue onto the backs of castrated male nude mouse recipients. The grafted tissue became vascularized and the small seminiferous tubules present at transplantation grew in size.
“We found motile sperm after xenografting for ten months. Some grafts survived for 17 months and viable sperm could still be obtained. So we think [obtaining xenografted sperm] mainly depends on the healthy condition of the nude mice,” Sun told Asian Scientist Magazine.
Xenograft-derived sperm where then injected into donor eggs and implanted into a total of 53 female surrogate monkeys. Eight of the females became pregnant, resulting in seven live births, one of which died three days after birth. The six remaining monkeys showed no observable difference from control monkeys in terms of their body weight, abdominal and head circumferences and head-truck length at six months after birth. Nevertheless, the authors cautioned that long-term health outcomes remain to be determined.
“Our results demonstrated that testicular xenografting could markedly shortened the reproduction cycle required for sexual maturity and pregnancy in cynomolgus monkeys,” Sun said. “In the wild type donor group, we can get mature sperm in two years. Thus, the testis xenografting method may facilitate the development of genetically modified monkey models.”
Although Sun hopes that the method will be able to help restore the fertility of cancer patients undergoing treatment in the future, he notes that many more detailed studies still need to be conducted.
“In the meantime, we are focusing on generating various gene-modified monkey models, and achieving F1 models as soon as possible. We also want to optimize our protocol of monkey testicular xenografting and make the monkey reproduction cycle shorter,” he added.
The article can be found at: Liu et al. (2015) Generation of Macaques with Sperm Derived from Juvenile Monkey Testicular Xenografts.
Copyright: Asian Scientist Magazine; Photo: Sun Qiang/Chinese Academy of Sciences.
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