Sperm created in the laboratory from embryonic stem cells produce viable progeny

Nayernia et al. derived male gametes entirely in vitro from embryonic stem cells, and demonstrated that they are functional and able to produce viable offspring. The background of the cover image shows an in vitro derived sperm, while the foreground displays mouse pups resulting from intracytoplasmic injection of such sperm into eggs.The authors suggest that this technology will provide a valuable assay both for the genetic dissection of germ cell development and for epigenetic reprogramming, and may one day facilitate nuclear transfer technology and infertility treatments.

Scientists have demonstrated for the first time that embryonic stem (ES) cells cultured in the laboratory can produce sperm with the capacity to produce viable offspring. The research, published in the July issue of Developmental Cell, opens many exciting avenues for future studies, including investigation of mechanisms involved in sperm production and development of new treatment strategies for infertility.

Previous studies have shown that ES cells grown in the laboratory can differentiate into primordial germ cells that then give rise to cells resembling mature egg and sperm cells, known as gametes. However, the functionality of the gametes has not been thoroughly tested and many questions about the viability of these cells remain unanswered. Dr. Karim Nayernia and Dr. Wolfgang Engel from the Institute of Human Genetics at the University of Goettingen in Goettingen, Germany and colleagues developed a new strategy for generating mature sperm cells in the laboratory using ES cells from mice and went on to test the functionality of the ES-derived sperm.

ES cells were treated with specific factors know to direct sperm production and screened for characteristics associated with primordial and spermatagonial stem cells. The researchers demonstrated that these cells could be further differentiated into mature sperm in the laboratory or could be transplanted into the testes of mice where they retained the capacity develop into sperm. Intra-cytoplasmic injection of the ES-derived sperm into mouse eggs resulted in successful fertilization and the resulting early stage embryos were successfully transplanted into mice. Six of the seven mice born developed into adult mice.

The results of this study establish that the ES cell derived cell lines can produce functional sperm in the laboratory which can be used to successfully fertilize eggs and support full-term development into embryos and adult mice. "Our approach provides an accessible in vitro model system for studies of mammalian gametogenesis, as well as for developing new strategies for generation of transgenic mice and may one day facilitate nuclear transfer technology and infertility treatment," offers Dr. Nayernia.

This work was supported by a grant from the Forschungsfoerderungsprogramm Stammzelle to K.N. of the University of Goettingen. Publishing in Developmental Cell, Volume 11, Number 1, July 2006, pages 125–132. www.developmentalcell.com/

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