Scientists claim sperm cell first

 

Controversy today surrounded claims that British scientists have made medical history by creating human sperm in the laboratory.

The Newcastle researchers said they had produced fully mature, functional cells which they called In-Vitro Derived (IVD) sperm.

But experts today cast doubt on the claim, arguing that the cells did not constitute “authentic” sperm with all the necessary biological characteristics.

The scientists led by Professor Karim Nayernia at Newcastle University and the NorthEast England Stem Cell Institute (Nesci) created the sperm from human embryonic stem cells.

The cells were observed to split and divide and then eventually push out a tail and begin to move.

Prof Nayernia’s team called for the introduction of laws “sooner rather than later” to control how the research is used.

The scientists stressed they had made no attempt to fertilise human eggs with the sperm.

Prof Nayernia said the development would lead to a better understanding of why infertility happened in men, and what caused it.

He said: “This understanding could help us develop new ways to help couples suffering infertility so they can have a child which is genetically their own.

“It will also allow scientists to study how cells involved in reproduction are affected by toxins, for example, why young boys with leukaemia who undergo chemotherapy can become infertile for life — and possibly lead us to a solution.”

The team also believes that studying the process of forming sperm could lead to a better understanding of how genetic diseases are passed on.

Stem cells are immature “mother” cells that can develop into different cell types. Those obtained from early-stage human embryos can theoretically be used to produce any kind of tissue in the body.

The technique developed at Newcastle involved prompting embryonic stem cells to become “germline” stem cells — cells that can pass their genetic material to future generations.

The cells contained pairs of XY chromosomes, defining them as “male”. Next, they were coaxed to complete the process of meiosis — cell division resulting in daughter cells with half the original chromosome set. Some cells would have ended up with an “X” chromosome and some with a “Y”. Meiosis is essential for the creation of both eggs or sperm.

In this case, the scientists produced cells which they described as “fully mature, functional sperm”.

The research is reported today in the journal Stem Cells and Development.

Prof Nayernia’s team said the sperm would not and could not be used for fertility treatment.

The scientists said as being prohibited by UK law, fertilisation of human eggs and implantation of embryos would hold no scientific merit for them as they wanted to study the process as a model for research.

Prof Nayernia said: “While we can understand that some people may have concerns, this does not mean that humans can be produced ‘in a dish’ and we have no intention of doing this.

“This work is a way of investigating why some people are infertile and the reasons behind it. If we have a better understanding of what’s going on it could lead to new ways of treating infertility.”

He said the research was in its early stages and more investigation was needed to decide whether IVD sperm would be safe or suitable as a fertility treatment.

He believed that in a decade such a treatment could be offered to, for example, young boys who had received chemotherapy which can leave them infertile.

“When combined with other pioneering stem cell techniques, specifically somatic cell nuclear transfer, it could also allow men who are currently infertile the chance to have a child which is genetically their own but again, this will be many years away — at least a decade.

“Given the speed of progress in this area of work, legislation needs to be put in place sooner rather than later to allow for the technique to be licensed as a treatment in the future for infertile men.”

However, other experts commenting on the work expressed doubt about what had been achieved.

Dr Allen Pacey, senior lecturer in andrology at the 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’.

“While 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.”

Professor Azim Surani, from Cambridge University, 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 these sperm-like cells are properly reprogrammed with male-specific imprints, without which they cannot function properly in early embryos.”

Professor Robin Lovell Badge, from the Medical Research Council Institute of Medical Research, said the work was a follow-up to animal research in which laboratory-made mouse sperm was used to produce offspring. However, all the mice born died after a few months, suggesting a problem with the sperm.

The Newcastle scientists had not produced robust evidence that the human sperm they created was normal, said Prof Lovell Badge.

Prof Lovell Badge said: “Although they find that some of the sperm cells have tails and can swim, this is not evidence of normality..”

Only a small proportion of the cells were “haploid” — having the necessary reduced genetic material following meiosis.

Dr Evan Harris MP, who tabled amendments to the 2008 Human Fertilisation and Embryology Bill on laboratory-made eggs and sperm 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.”

Approximately one in seven couples have fertility problems.

In 20 per cent of couples, low sperm count or quality is the only cause of infertility, and it is a contributory factor in a further 25 per cent of couples. In 30 per cent-50 per cent of men, no cause is identified for the poor sperm characteristics.

The NorthEast England Stem Cell Institute (Nesci) is a collaboration between Newcastle and Durham Universities, Newcastle NHS Foundation Trust and other partners.