Stem cells may hold the answer to reversing male infertility
There has been another breakthrough in stem cell research which may have implications for the future of male fertility. Scientists in China have created working sperm cells from embryonic stem cells. While the sperm were not mature, they were sufficiently advanced to create nine fertile offspring born following the successful injection into female mice eggs1. The results of this study raise questions about the potential for stem cell research to enable infertile men to father their own children.
What are stem cells?
Stem cells are different from normal cells. They are specialised cells with the ability to renew through cell division. This process can still occur after long periods of inactivity. Under certain influences, these cells can be manipulated to develop into organ or tissue specific cells with certain functions.
Pluripotent stem cells, more commonly known as embryonic stem cells (ESC), are found in the embryo, foetus, placenta, amniotic fluid, and umbilical cord blood. These cells can give rise to any type of cell in the body. In adults, tissue stem cells are also present and can typically only give rise to cells of the parent tissue.
The majority of stem cell research involves ESC due to their non-specific nature and ability to be manipulated. This type of research is often considered controversial because it involves the destruction and use of human embryos.
The mice experiments
In this new Chinese study the scientists used ESC extracted from mice. As these cells can develop into any type of cell, the multistage meiosis process is extremely hard to control. In 2011 a team of researchers from the Kyoto University in Japan managed to turn mouse ESC into cells resembling primordial germ cells (PGCs)2. These are the cells which can develop into spermatozoa and oocytes. The findings from this study lead by Mitinori Saitou were very important and have subsequently been utilised in this recent research.
In the 2011 study, Saitou and colleagues injected the cultured PGCs into the testes of infertile mice. Subsequently, these stem cells matured into sperm and the mice were able to father healthy offspring. Although these results were groundbreaking there were too many unknown factors.
Injecting PGCs into the testes for maturation meant that the scientists could not observe the following meiosis and potential complications. If a similar clinical approach was applied to human males there is a large risk of tumor development in the testes.
However, based on the latest research no transplantation may be necessary. Researchers from the Nanjing Medical University in China and the Chinese Academy of Sciences in Beijing used the findings of previous studies by Saitou and others to significantly progress this research.
Xiao-Yang Zhao and colleagues were able to produce PGCs as previously done in earlier studies. Then through hundreds of trials they combined these cells with testicular cells from young mice in an array of culture conditions. Eventually they identified a mixture of hormones and growth factors that promoted cell division normally observed during meiosis.
The resulting sperm-like cells were then injected directly into the eggs of mice. Although these cells were very immature and could not swim, the IVF procedure was successful and healthy fertile mice were conceived. During this process the researchers were able to monitor the meiosis process in vitro. This provided a new insight into stem cell research.
What does this research mean for human male infertility?
The findings of this research have been met with caution within the scientific community. The reality is that clinical applications in human men are very remote. Human and mouse germ cells develop very differently. Most likely they would also need very different conditions. However, the concept itself is encouraging.
Ultimately there are many more years of research to be done in this area of ESC research. Zhao and the team are already planning new studies with the aim to replicate their findings. There are already trials underway using monkeys. We will have to wait for the outcomes of these studies before further conclusions can be made.
- “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)” ↩
- “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)” ↩