Researchers create human sperm using embryonic stem cellsBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2790 (Published 09 July 2009) Cite this as: BMJ 2009;339:b2790
Researchers have created human sperm using embryonic stem cells for the first time, in research aiming to improve the understanding of male infertility and the transmission of genetic disorders.
A team from the NorthEast England Stem Cell Institute developed the new technique, which enables human sperm cells to be produced in the laboratory. They used human embryonic stem cells with male and female chromosomes (XY and XX) to develop male germline stem cells. Only XY cells were then prompted to complete meiosis—cell division that halves the number of chromosomes. These cells then developed into fully mature, functional sperm, called in vitro derived sperm (IVD sperm) (Stem Cells and Development 2009;8 Jul online, doi:10.1089/scd.2009.0063)
“While the full potential of the human embryonic stem cell derived sperm remains to be demonstrated, this in vitro modeling of human gametogenesis provides a new approach for studying the biology of human germ cells and the establishment of therapeutic approaches in reproductive medicine,” say the researchers, led by Professor Karim Nayernia, professor of stem cell biology at Newcastle University.
Embryonic stem cells have nearly unlimited capacity for self renewal and differentiation into specific cell types. However, the Newcastle researchers noted that it has proved “rather challenging” to direct the differentiation of human embryonic stem cells into specific lineages.
They based their technique for human sperm cell production on understanding the mechanisms underlying cell lineage decisions during early embryogenesis. They tracked the profile of the cell markers expressed by cells that develop into germ cells, and then grew embryonic stem cells in a cell medium that encouraged differentiation into these cell types. Cells expressing the required markers were separated out by staining key surface proteins with a fluorescent marker. This picked out cells producing proteins coded for by a gene (Stra8) required for spermatogenesis.
The final sperm cells were haploid and motile, which are essential characteristics of male gametes. Some of the motile cells had tail-like structures, similar to the flagellae of human sperm cells.
“These results clearly demonstrate that human embryonic stem cells are able to differentiate to adult male germline stem cells, which can produce sperm-like cells,” the group said.
Professor Nayernia noted, “This is an important development as it will allow researchers to study in detail how sperm forms and lead to a better understanding of infertility in men—why it happens and what is causing it. This understanding could help us develop new ways to help couples suffering infertility so they can have a child which is genetically their own.”
He explained that sperm production in humans (from primordial germ cells to sperm cells) takes more than 15 years, making it difficult to study, adding, “Now that we have a technique for producing sperm in two to three months, we can study different factors, including environmental and genetic factors, that affect sperm development.” Male infertility is a growing problem, particularly in developed countries, but the cause has previously been unclear.
The technique could also be used to identify the cause of infertility in individual men, using isolated skin cells to produce stem cells that could then be used to develop in vitro derived sperm. “We can then use these cells to trace the cause of infertility and offer the correct therapeutic approach,” Professor Nayernia explained.
The technique will also make it possible to study how cells involved in reproduction are affected by toxins—for example, why young boys with leukaemia treated with chemotherapy can become infertile for life—with the aim of developing a solution. Studying the process of sperm development could also lead to a better understanding of how genetic diseases are passed on.
However, the research team emphasised that the new technique will not be used to create sperm to be used for fertility treatment with the aim of producing a baby—this is prohibited by UK legislation.
Cite this as: BMJ 2009;339:b2790