Sperm 'made from stem cells'

Men and women may no longer be needed to create babies, according to the front page of the Daily Mail, which says that scientists have created “sperm and eggs from stem cells”. Other newspapers predict that the research could lead to human sperm being produced within five years.

The researchers in this laboratory study have managed to take stem cells from human embryos and follow them as they become germ cells, which are the embryonic cells that evolve into sperm and eggs. They showed that some of these germ cells can be made to divide into cells that have many of the properties of sperm cells, but which may not be considered to be actual sperm.

The purpose of the work was to create a laboratory method for studying how human sex cells develop, and not to directly aid fertility. The work could have implications for future infertility research, but was very preliminary.

The researchers did not attempt to use the cells for fertilisation, and it is not clear if the cells had the ability to do so. It is therefore too soon to say that scientists have discovered a way to create sperm and eggs without men or women.

Where did the story come from?

The research was carried out by Dr Kehkooi Kee and colleagues from the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine in California. It was supported by several grants from bodies including the National Institutes of Health and the California Institute for Regenerative Medicine. The study was published in the peer-reviewed science journal Nature.

What kind of scientific study was this?

The researchers in this study were interested in how human sperm and eggs develop. This process is hard to study as it occurs very early in human embryo development, before the embryo is two weeks old. For this reason, the process has only so far been examined in animals.

However, as the processes in humans may be different, the researchers wanted to see if they could develop a technique to study human germ (sex) cell development in the laboratory.

In this study, the researchers particularly wanted to see if they could get human embryonic stem cells to develop into cells that could undergo meiosis. Meiosis is the critical process of cell division in which cells with two copies of each chromosome divide to form into sperm or eggs, which contain one copy of each chromosome.

The researchers hoped this work could be used to further the understanding of how human germ cells develop, and how problems in this process might lead to infertility.

The researchers employed a technique that would allow them to identify those cells that had developed into germ cells. They took human stem cells from embryos and added a gene that causes green fluorescence in the cells when the VASA gene is turned on. This is a gene found only in germ cells, so only the cells that became germ cells in future tests would be marked bright green.

The researchers then studied the cells from their early formation and looked at the way they progressed through cell division to eventually specialise and transform into germ cells. They studied four types of cell that originally came from two male and two female embryos.

They were also interested in the role of three genes called DAZL, DAZ and BOULE in this process. The DAZL gene is involved in the early formation of the precursors to sperm and eggs, while the other two closely related genes, DAZ and BOULE, promote the later stages of development. Mutations in these genes are associated with human infertility but their exact role in early sperm and egg development had not previously been studied in such detail.

Tests confirmed that the green fluorescing cells behaved like normal early germ cells and then the researchers turned the actions of the three genes on and off. They did this to see if the genes were critical in the developmental path from stem cell to sperm and egg cells, and counted how many of the germ cells were formed.

What were the results of the study?

The researchers found that they could get human embryonic stem cells to develop into cells that had some of the genetic characteristics of germ cells. They found that the DAZL gene was necessary for this transformation. When DAZL was turned off, only half as many germ cells formed. DAZ and BOULE acted later in the germ cells’ developmental path, encouraging cells into meiosis.

In 'male' cells (from male embryos) that had all three of the genes switched on, around 2% had completed meiosis after two weeks in the laboratory. Their number of chromosomes had reduced by half, a key early stage in the development of mature sperm. These cells also had activated genes that are found in sperm, and were round in shape like cells in the earlier stages of sperm development (previously they had not yet developed the typical tails of mature sperm).

The researchers say that eggs can stay in the state of incomplete meiosis for many years, and the 'female' cells had not gone as far towards completing meiosis. This was the closest the cells got to being true sperm or egg.

What interpretations did the researchers draw from these results?

The researchers say that their results indicate that germ cells can be produced from human embryonic stem cells and made to develop and grow through to the cell division known as meiosis. They say that the human DAZ gene family controls the process, and that their research has significance for future scientific research and clinical applications.

What does the NHS Knowledge Service make of this study?

The work illustrates the potential of stem cell research and will no doubt add to scientists’ knowledge of how sperm and eggs are formed. To suggest that healthy sperm and eggs can already be produced in this way, as have some newspapers, is overstating the case.

Researchers and most newspapers have correctly identified that this work is early research, and that its importance lies in furthering the understanding of sperm and egg development and perhaps the development of future treatments for infertility. It is worth noting that:

• The researchers plan to test the same techniques with adult types of stem cells rather than those from embryos, but there is no indication yet as to whether these cells will behave in the same way.
• The cells produced by this process can’t yet be called sperm or eggs, and it is not possible to say yet if these cells could be successfully fertilised by each other. Even if healthy sperm and eggs could be produced, using techniques not yet developed, it is not clear what the implications would be for the complex processes that occur after fertilisation.
• The main value of the study, as described by its authors, is that they have developed a laboratory system that can be used to help them understand some of the potential causes of adult infertility.