Behrouz Aflatoonian will tell the 21st annual conference of the European Society of Human Reproduction and Embryology today (Monday 20 June) that the research also solves the practical and ethical problems associated with obtaining human samples of primordial germ cells (PGCs), which are the ancestral cells that eventually form eggs and sperm (gametes). "Investigating the mechanisms of human primordial germ cell and gamete development is important for understanding the causes of infertility and the potential harmful effects of environmental chemicals on reproductive development," he will say. "But at present it is very difficult to obtain human samples of these cells as they only occur early in development."
Mr Aflatoonian, who is a PhD student in Professor Harry Moore's laboratory at the Centre for Stem Cell Biology, University of Sheffield, UK, said that studies with mice embryonic stem cells had shown that they were capable of differentiating into PGCs and subsequently eggs and sperm, so he set out to see if the same applied to human embryonic stem cells (HESCs).
"We derived six embryonic stem cell lines from embryos donated for research under HFEA regulations by couples undergoing IVF treatment. In addition, we utilised cell lines from the University of Wisconsin.
"The human embryonic stem cells were allowed to develop into collections of cells called embryoid bodies. The embryoid bodies were tested to see which genes were active, or 'expressed', in them and it was found that within two weeks a very tiny proportion of cells in the embryoid bodies began to express some of the genes that are found in human primordial germ cells. Some cells also expressed proteins only found in maturing sperm. This suggests that HESCs may have the ability to develop into PGCs and early gametes as has been shown previously for mouse embryonic stem cells."
However, Mr Aflatoonian stressed that there was still a lot of work to be done before the promise of these early results could be translated into reality. "Embryoid bodies can differentiate into all sorts of tissue types, so we need to choose the cells that are going to develop into PGCs and then work out how we can encourage them to grow into gametes.
"Producing functional gametes is much more difficult, because we have to recreate for the cultured cells the environment of the developing follicle for egg development or the tissue of the testis for sperm. We want to test whether HESCs can differentiate to cells that produce the hormones for sperm and egg development and isolate these as well. What is extraordinary is that the embryoid bodies seem to produce spontaneously the tissue and environment conducive for sperm and egg development in quite a short time in culture."
Speaking before the conference, Prof Moore said: "One of the reasons for doing this research is that it may allow us to investigate the very earliest processes of how a human gamete and gonad (ovary and testis) develops. Many scientists believe that environmental chemical pollutants that mimic the action of hormones (so called endocrine disrupting chemicals) might interfere with human development at this stage and cause congenital abnormalities, infertility and possibly cancer (in particular testicular cancer). By developing suitable tests with embryonic stem cells as they differentiate to germ cells we can investigate the action of these chemicals in the laboratory.
"Ultimately it might be possible to produce sperm and eggs for use in assisted conception treatments. This is a long way off and we would have to prove it was safe because, for example, the culture process may cause genetic changes. For some men and women this would be the only route for producing sperm and eggs. It would not be reproductive cloning as fertilisation would involve only one set of gametes produced in this way and therefore a unique embryo would form.
"In addition, if we could produce eggs from HESCs they could also be used for therapeutic cloning (somatic nuclear replacement) circumventing the need for eggs from patients who donate them, as this is a major limitation of this technique at the moment. We would then have completed the circle of making HESCs from eggs that came from HESCs - what came first the chicken or the egg?!"
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