New developments in stem cell research
New developments in stem cell research may mean a breakthrough in the treatment of future male infertility. Using mice embryonic stem cells (ESC), researchers in China have been able to recreate working sperm cells.
Despite not being fully mature, these cells were still advanced enough to father fertile offspring after successful IVF treatment in female mice[1. “Zhou, Q. et al. (2016).
Complete meiosis from embryonic stem cell-derived germ cells in vitro. Cell Stem Cell. Volume 18, Issue 3, (pp. 330-40).”]. Now scientists are looking ahead in the potential to replicate these results in humans. This raises the question, could infertile men become fertile with advances in human ESC research?
What are embryonic stem cells (ESCs)?
Stem cells are highly specialised cells and different from all other types of cells. These cells have the ability to replicate through cell division, even after times of inactivity. Scientists have found ways to manipulate stem cells into forming specific tissues or organs within the body.
There are different types of stem cells. The majority of research focuses on ESCs because these cells can give rise to any other type of cell. This makes ESCs malleable under certain conditions. Umbilical cord blood, embryos, foetus, placenta, and amniotic fluid all contain ESCs. Stem cell research is often seen as controversial as it requires the use of human embryos.
Turning stem cell into oocytes and spermatozoa
The recently published Chinese study utilised ESCs from infertile male mice to create viable sperm capable of fertilisation. This ground breaking research was partly made possible by earlier studies by Mitinori Saitou and colleagues. In 2011 this Japanese based research team from Kyoto University successfully transformed mouse ESCs into cells similar to primordial germ cells (PGCs)[1. “Hayashi, K. et al. (2011). Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells. Cell. Volume 146, Issue 4, (pp. 519-32)”.].
This was a core research finding as ESCs can develop into any cell type and it’s very difficult to control the multistage meiosis to form germ cells. From these cells, oocytes and spermatozoa develop.
The cultured PGCs were injected into infertile mice testes. The primordial germ cells further developed into mature spermatozoa and the subject mice went on to father healthy offspring. This research formed the foundations for this latest study.
Using ESCs in IVF
Although the preliminary research by Saitou and colleagues was promising, there are unknown factors. As the PGCs were injected into mice testes for maturation it wasn’t possible to review the process of meiosis and identify any potential complications. This approach would be too risky in human males due to the possible tumor development in the testes.
This is where the recent research from Xiao-Yang Zhao and colleagues become groundbreaking. Using the findings of Saitou and others, Xiao-Yang Zhao and colleagues were able to replicate PGCs. Subsequent trials combing these cells with testicular cells from mice were used to identify optimal growth factors necessary to support healthy cell division.
These non-motile immature sperm-like cells where injected into mice eggs. The IVF treatment was successful and fertile healthy mice were born. Throughout the experiment researchers had the opportunity to witness meiosis in vitro. This new insight into stem cell research may have implications for human male infertility.
Could human male infertility be reversed with stem cell research?
Although the mice experiments have been groundbreaking the scientific community is viewing the results with caution. Human clinical applications are currently considered remote. Germ cells of humans and mice develop differently. Nevertheless, the concept is still encouraging.
New studies are already planned and underway to further explore the findings of Zhao and colleagues. While there are many years of ESC research ahead, it is possible that this area of scientific endeavour may hold some hope for infertile men wanting to father their own children.
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Dr. Kooner is Deputy Director of The Advanced Fertility Center of Chicago and has been a Specialist in Fertility Treatment since 1999.
As well as the areas that the clinic specialises in general, he is particularly interested in managing oocyte donation, female same-sex couples, single women having sperm donation and those considering egg freezing.
Dr. Kooner regularly speaks at fertility meetings. He has published in national journals and constantly contributes to the fertility research and publications from Advanced Fertility Center of Chicago.
