Artificial sperm cells to remove the genetic worries of sperm donation

Grady, the first non-human primate to be born using sperm cells isolated from transplanted testicular tissue.

Published 12 December 2019

A Campus meeting in November reviewed the arguments for and against donor conception, and the sometimes difficult ethical arguments raised by the prospect of a donor-conceived child. 'Artificial' sperm cells derived from testicular tissue or stem cells may resolve some of those arguments.

Conclusions from a wide-ranging Campus meeting on the relevance of genetic inheritance in the outcome of fertility treatment seemed to rest on the balance between biological parenthood and treatment success. However, according to one presentation, the creation of sperm cells naturally derived from banked testicular tissue or spermatogonial stem cells, may render redundant any such genetic inheritance concerns arising from cancer treatment in young men and boys. Such a scenario is still a long way off, said Ellen Goossens from the Vrije Universiteit Brussel, but more than 1000 young subjects already have testicular tissue banked for fertility preservation, with proof of concept already reported in primate models. 'Spontaneous pregnancy is now possible,' said Goossens, with reference to Grady, the graft-derived baby born in the USA and reported last year.

The problem is especially acute in cancers diagnosed in prepubertal boys in whom there are no sperm cells available for storage. Their only option for future fatherhood in the face of cancer treatment is adoption or donor sperm. And this, added Goossens, is not an exceptional problem. Incidence rates are around 17 cases per 100,000 population, with leukemia and CNS tumours the most commonly diagnosed. So the usual pathway to fertility preservation in these young cases is for the oncologist to warn of the risk to future fertility from the cancer treatments and refer to the fertility clinic. Biopsy of testicular tissue, of course, must be performed before any radio- or chemotherapy.

Goossens described two experimental techniques, spermatogonial stem cell retrieval and transplantation, and homotopic tissue grafting. The danger in the former procedure is a risk of introducing malignancy, so banked tissue must be free of malignant contamination. Experiments in mouse-to-mouse models have demonstrated spermatogenesis from tissue grafting, and most recently fully functional conception and delivery in a non-human primate (Grady). Similarly, experiments in mouse models with spermatogonial stem cell transplantation have so far proved efficient, with spontaneous pregnancy already possible.

Of course, the objective of this impressive experimental work is not merely a resolution to the question of genetic continuity in couples faced with third-party donation, but the future fertility and long-term quality of life of so many unfortunate young boys. Advances in cancer treatment have led to the increased survival of all children with cancer, and with it a new imperative for the restoration of their fertility. Not all cancer treatments cause complete testicular damage, but around one-third of children having treatment for pediatric cancers will end up infertile. Following the proof-of-concept study which saw the birth of Grady - in which testicular samples removed from prepubertal monkeys was frozen, thawed and regrafted under scrotal skin - the research group declared that their next logical step, with safety and feasibility apparent, is human trials.

1. Fayomi AP, Peters K, Sukhwani M, et al. Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring. Science 2019; 363: 1314-1319.

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