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Scientists at Newcastle University have demonstrated the creation of sperm-like cells from human embryonic stem cells, which could be a means of understanding and treating male infertility. However, experts questioned to what extent the resulting cells could be described as ‘true sperm’, describing them more as ‘sperm-like’ cells.
Prof Karim Nayernia, Newcastle University, the lead author on the paper, said:
“The research paper published today (Wednesday, 8 July) is clearly labelled as ‘proof of principle’, and concludes that further research is needed in this area. It seems unreasonable to criticise our work on the basis that we have not done more, when we never claimed to have gone beyond proof of principle.
“Our intention was to open up new avenues of research with these early findings. My research group believes this is a very important and exciting step forward and we will continue to develop this area of research.”
Dr Allan Pacey, Senior Lecturer in Andrology, University of Sheffield, said:
“As a sperm biologist of 20 years experience, I am unconvinced from the data presented in this paper that the cells produced by Professor Nayernia’s group from Embryonic Stem Cells can be accurately called ‘Spermatozoa’.
“Whilst the cells produced may possess some of the distinctive genetic features and molecular markers seen in sperm, fully differentiated human spermatozoa have specific cellular morphology, behaviour and function that are not described here.
“The video clip does not have sufficient resolution for me to observe how these cells are moving, and since motility is an important part of sperm behaviour, it would seem important to assess this in some detail.
“Furthermore, because the structural elements of spermatozoa are very distinctive, I would need to see thin sections of the putative sperm taken with an electron microscope and compare them to how we know the head, midpiece and tail of mature sperm are constructed.
“In spite of my perhaps negative comment, I am supportive of research efforts to try and make in vitro derived spermatozoa in the laboratory since, if it was ever successful, it could help us answer some important questions about how sperm are made and why some men are sub-fertile.”
Prof Azim Surani, Professor of Physiology and Reproduction, University of Cambridge, said:
“These sperm-like cells made in a dish from embryonic stem cells are a long way from being authentic sperm cells. First, they need to test if a normal male pronucleus with appropriate chromosome numbers and without mutations can form when introduced into an animal egg; and there has to be evidence that theses sperm-like cells are properly reprogrammed with male-specific imprints, without which they cannot function properly in early embryos.”
Prof Robin Lovell Badge, MRC National Institute of Medical Research, said:
“This paper is a follow up to work published in 2006 by the same group where it was claimed that mouse sperm could be derived in vitro (in culture in the lab) from pluripotent mouse embryonic stem cells. These sperm were used to fertilise mouse eggs by intracytoplasmic sperm injection (ICSI), and several mice born, but they all died after a few months, suggesting that the sperm were not normal.
“In the current paper they have followed similar methods with human embryonic stem cells and claim to have obtained sperm from these, which carry half the normal number of chromosomes (a haploid set is 23, whereas precursor germ cells and most somatic cells are diploid with 46). If true, the latter indicates that they have been through the process of meiosis, an essential hallmark of male germ cells that could go on to fertilise an egg. They have not attempted to fertilise human eggs with these, a very reasonable decision since they need much better evidence that such in vitro-derived sperm are normal. Although they find that some of the sperm cells have tails and can swim, this is not evidence of normality or even that the cells are haploid. Perhaps more of a problem, although not a surprise given that no special methods were employed to direct the cells to make sperm, is that the proportion of the germ cells that appeared to be haploid was very small (3.1 %) and indeed even these results are not very robust – the analysis seemed to suggest a wide range of chromosome number. If the sperm-like cells are really haploid, then they should have either an X or a Y chromosome as the original Embryonic Stem cells were XY (male). However, we are shown only one example of each, it would be good to see the statistics on this. Despite these drawbacks, it may be that the authors have made some progress in obtaining sperm from human Embryonic Stem cells in vitro. This will be very important for research and ultimately, although definitely not yet, for fertility treatments. But far more robust methods are needed than those described here.
“I am also very pleased to see that Professor Nayernia is no longer claiming that it might be possible to obtain sperm from XX (chromosomally female) Embryonic Stem cells. It has long been known that genes on the Y are required to make sperm.”
Dr Evan Harris MP, Liberal Democrat science spokesman, said:
“While the Newcastle team is not seeking at present to use stem cell derived sperm as a treatment for infertility, it is clearly a possible future application. It is very sad that the recent Human Fertilisation and Embryology Act did not take the opportunity to provide a power for Parliament to approve clinical trials of stem cell (IV) derived sperm as a treatment for male infertility by regulations.
“Instead the actual use of these gametes – even when derived from adult stem cells where no embryo is used – in the treatment of infertile couples will require primary legislation. This makes it more difficult to attract funding for the application of this research despite the Government always banging on about the importance translational research.”
Dr Harris tabled amendments to the 2008 Human Fertilisation and Embryology Bill on IVD gametes to seek to speed up their potential use in fertility treatment.