The Results are Only Preliminary, the Researchers Warn:
Human embryos stem cells have been convinced to form sperm-like cells, researchers report today. The cells have some of the hallmarks of sperm (they can swim, for example), but they require much more characterization before they can be accepted as an experimental model for the study of hereditary diseases and infertility.
Meanwhile, the use of such cells to help infertile couples have children remains a distant perspective; in several countries, including the United Kingdom, it would actually be illegal even if they were properly characterized. With approximately one in seven couples experiencing fertility problems, there is a strong impulse to develop a solid method to generate sperm and ovules for research. But researchers have struggled for years to produce reproductive cells from stem cells. The task is particularly difficult because it requires a complex form of cell division called meiosis, which halves the number of chromosomes per cell. “If these genes are not modified correctly, it is as if you erase a hard drive but you did not do it very well.” In addition, DNA packed into reproductive cells is cleaned of a chemical modification known as methylation, which involves the binding of methyl groups to certain regions of the genome. These modifications are added again in characteristic patterns of sperm cells or ovules.
“Methylation can affect gene expression, and if demethylation or remethylation does not occur properly, the results can be disastrous”.
“If these genes are not modified correctly, it is as if you erase a hard disk but you did not do it very well,” says Renee Reijo Pera, director of the Center for Research and Education of Human Embryonic Stem Cells at the University School of Medicine from Stanford. in Palo Alto, California. “The embryo can develop and some babies are born, but there could be serious abnormalities . ” Possible evidence for this was observed in 2006, when Karim Nayernia, now from the University of Newcastle Upon Tyne, United Kingdom, and colleagues reported that they had produced sperm from mouse embryonic stem cells. When sperm were used to fertilize mouse eggs, the few offspring that were born died prematurely. Nayernia says his lab is still working to determine what went wrong, but the first results suggest that the DNA in the sperm was not properly remethylated.
From Mice to Men:
Now, Nayernia and his colleagues have used a similar technique to create sperm-like cells from human embryonic stem cells. The team labeled embryonic stem cells with a fluorescent marker attached to a particular gene that is expressed during the development of reproductive cells, and cultured the cells in a medium that promotes differentiation into sperm cells. About 3% of the resulting cells contained enough DNA for a single set of chromosomes, suggesting that meiosis had occurred. Some of these cells also formed tails and were mobile. The work is “a good start,” says Reijo Pera, who was not affiliated with the study, but an additional characterization of these cells will be needed before they can be considered as an experimental model for the study of sperm. Nayernia and his colleagues have not yet analyzed the methylation patterns in their sperm cells, nor have they conducted a detailed study of cell morphology. Robin Lovell-Badge, head of the Division of Stem Cell Biology and Developmental Genetics at the National Institute of Medical Research in London, notes that the Nayernia team observed only the total DNA content of the cells, and did not confirm that they contained The right number of chromosomes. “You need to identify supposed haploid cells and verify that they really have all 23 chromosomes and no more,” says Lovell-Badge.
But Nayernia says that the work is a “proof of principle experiment . ” “We don’t claim to be a completely normal sperm, but they have some of the right characteristics.” These problems would have to be tackled carefully before attempting to fertilize a human ovum with the cells, but some preliminary tests of the ability of sperm-like cells to behave like sperm could be performed. For example, sperm should be able to bind to the membrane that surrounds unfertilized egg cells, regardless of whether there is an egg inside, says Reijo Pera. Meanwhile, Nayernia and his colleagues also launched a project to produce sperm cells from induced pluripotent stem cells, which can be generated from adult cells. Such cells would facilitate the obtaining of sperm cells from many individuals. “Then we can, for example, see if environmental or genetic factors are affecting fertility, and what stage of sperm production has been affected by those factors,” he says.