Male infertility: Stem cells to the rescue?

Author: Angela C. H. McDonald, 11/27/12

Last month, I blogged about recent stem cell advances toward a solution for female infertility. While this post may have left you excited about the potential for stem cells to help women with fertility complications start a family, it may also have left you wondering: “What about the other half?” After all, male infertility accounts for approximately 50% of infertility problems among Canadian couples.

While you were wondering, American researchers were getting set to publish an exciting clinical progress report describing the transplantation of sperm stem cells into primates resulting in the production of functional sperm. This research hit the stands this month in the most recent issue of Cell Stem Cell.

Spermatogonial stem cells are stem cells residing in the testes and are responsible for the maintenance of spermatogenesis (generation of spermatozoa, or sperm). These cells divide rapidly. Over the course of one day, spermatogonial stem cells will produce more than 70 million of those wiggly bad boys. This rapid cell division is great for maintaining a pool of sperm for reproductive purposes — however, for men undergoing chemotherapy or radiation cancer treatment, their quickly dividing spermatogonial stem cells also become the targets of these therapies, which are designed to take out fast dividing cells (cancer cells). In fact, testicular dysfunction is one of the most common long-term side effects of chemotherapy in male patients.

Approximately 100,000 Canadian men will be diagnosed with cancer in 2012, of which many will undergo chemotherapy or radiation treatments. Post-pubescent men undergoing cancer treatment can choose to cryopreserve sperm for future reproduction through assisted reproductive technologies. However, sperm cryopreservation is not possible in prepubescent boys who will undergo cancer therapies, as mature sperm are not yet produced.

Cell Stem Cell’s recent report gives some hope for preserving the fertility of prepubescent boys undergoing cancer treatment. In this study, testicular biopsies were obtained from non-human primates and used for the isolation of spermatogonial stem cells. The researchers labeled spermatogonial stem cells with a fluorescent label and transplanted the cells into the testes of the same animal (autologous transplantation) as well as into the tests of another animal (allogeneic transplantation) that had previously undergone infertility-inducing chemotherapy. In total, 23 primates, both adult and prepubescent were involved in the study. Interestingly, three months after transplantation 75% of the adult and 60% of the prepubescent recipients within the autologous cohort had stable donor sperm. Results were not quite so good in the allogenic cohort, where stable donor sperm were detected in 33% of the recipients.

But having donor sperm was only half the equation. The real question was: Were they functional? To determine this, the researchers performed an aggressive form of in vitro fertilization (IVF) known as intracytoplasmic sperm injection where a single sperm is injected directly into an egg (standard IVF procedure is to passively combine sperm and eggs in a culture dish). Twenty-three per cent of the fertilized eggs developed into embryos with normal morphology. Unfortunately, the researchers lacked sufficient resources to transfer embryos into surrogate females to test the ability to generate viable offspring. Nonetheless, the development of normal looking embryos is very promising.

Patients around the world have already banked testicular tissue, hoping advances in reproductive technology would allow the use of these samples. While transplanting spermatogonial stem cells into human patients is still far off, perhaps one day this technology will be the solution patients have been waiting for.

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Angela C. H. McDonald

Angela C. H. McDonald

PhD candidate at Hospital for Sick Children
Angela is a PhD student in the Stem Cell and Developmental Biology program at the Hospital for Sick Children in Toronto. She is currently utilizing pluripotent stem cells to understand the genetic regulation of endoderm development. As an avid supporter of public science education, she co-founded the high school outreach initiative StemCellTalks sits on numerous public education committees including the International Society for Stem Cell Research Public Education Committee and the Stem Cell Network Public Outreach Committee.
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