The results indicate remarkable similarity between the gene expression and behavior of the ancient cells that govern reproduction, even between two species that diverged phylogenetically 75 million years ago. The study reveals much about the lifecycle of the male germline stem cell.
The results demonstrate relevance to the basic understanding of all stem cell types—which are frequently difficult to isolate in such highly enriched populations—but also provide hope to prepubescent men risking infertility due to cancer treatment. A clinical trial using this methodology is underway at CHOP.
“There is remarkable similarity between prepubertal human spermatogonia and mouse gonocytes, which is not only very surprising but quite informative considering the large separation between human and mouse,” said Ralph L. Brinster, a reproductive physiologist at the University of Pennsylvania School of Veterinary Medicine. “In our studies we found seven of the 100 most highly enriched genes between germ cells and somatic cells were conserved in human and mice, attesting to the fundamental importance of germ cells in species evolution.”
Even when human prepubescent germ cells were transplanted into mouse testes, the cells preserved themselves by migrating to the “basement” membrane of the seminiferous tubule where they were maintained for months. The expression of several novel genes known to be essential for stem cell self-renewal was high.
The ability of prepubertal human spermatogonia to migrate to the basement membrane of mouse testes and be maintained as germ cells, and likely spermatogonial stem cells (SSCs), lends biological support to the similarity of the two species’ germ cells. The relationship opens a window of opportunity to learn about human SSCs through studies on prepubertal human spermatogonia that can be identified and isolated in essentially pure populations and relating observations to the rapidly developing information base about mouse SSCs.
The research team, led by Brinster and Jill P. Ginsberg, pediatric oncologist with The Children's Hospital of Philadelphia, published the study, “Prepubertal Human Spermatogonia and Mouse Gonocytes Share Conserved Gene Expression of Germline Stem Cell Regulatory Molecules,” Dec. 14, 2009 in the journal Proceedings of the National Academy of Sciences.
The results have particular relevance to medical treatment of human infertility because of the critical role of these stem cells in male fertility. With cure rates of childhood cancer now approaching 80, about one in 640 individuals of reproductive age are now cancer survivors. However, many of these survivors will have fertility problems as adults. Cryopreservation of a testis biopsy in a tissue bank from boys undergoing cancer therapy is an option to preserve stem cells for later transplantation to restore spermatogenesis and is currently being examined in clinical trials. The results in the paper provide valuable information relevant to handling stem cells during cryopreservation and transplantation and also establish a foundation for culture studies on the stem cells.
The Children's Hospital of Philadelphia is currently offering testicular tissue cryopreservation as an experimental treatment option. The study began in January 2008 and includes 16 boys diagnosed with various solid tumors, ranging in age from 3 months to 14 years old. All were treated with chemotherapy or radiation, which carries a significant risk of resulting infertility. These boys had a tiny portion of their testis removed and frozen for their potential future use. The hope is one day to use frozen tissue from prepubescent males to restore fertility. Physicians would thaw the preserved tissue and reimplant it in the patient's testes, or use it for other assisted reproduction technologies.
"Even though there are currently no guarantees of clinical success, families are highly receptive to this option," said Ginsberg, who led the clinical arm of the research study. Results of that study, demonstrating whether parents would be receptive to the treatment option, were published online Oct. 27 in the journal Human Reproduction.
The National Institute of Child Health and Human Development supported this study, as did the Ethel Foerderer Award at The Children's Hospital of Philadelphia, and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.
The study was conducted by Brinster, Xin Wu, Jonathan A. Schmidt and Mary R. Avarbock of the Department of Animal Biology at Penn’s School of Veterinary Medicine; John W. Tobias of the Penn’s Bioinformatics Core; co-investigator Jill P. Ginsberg and Claire A. Carlson of the Division of Oncology at The Children’s Hospital of Philadelphia; and Thomas F. Kolon of the Department of Urology at The Children’s Hospital of Philadelphia.
Jordan Reese | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy