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Human Reproduction Update Advance Access published online on April 7, 2005
Human Reproduction Update, doi:10.1093/humupd/dmi007
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 13, 2004
Accepted March 9, 2005

Review

Efforts to create an artificial testis: culture systems of male germ cells under biochemical conditions resembling the seminiferous tubular biochemical environment

N. Sofikitis 1*, E. Pappas 2, A. Kawatani 3, D. Baltogiannis 4, D. Loutradis 3, N. Kanakas 4, D. Giannakis 4, F. Dimitriadis 1, K. Tsoukanelis 1, I. Georgiou 4, G. Makrydimas 4, Y. Mio 5, V. Tarlatzis 6, M. Melekos 7, and I. Miyagawa 2

1 Laboratory for Molecular Urology and Genetics of Human Reproduction, Department of Urology, Ioannina University School of Medicine, Ioannina, Greece, Department of Urology, Tottori University School of Medicine, Yonago, Japan
2 Department of Urology, Tottori University School of Medicine, Yonago, Japan
3 Department of Obstetrics and Gynecology, Athens University School of Medicine, Athens, Greece
4 Laboratory for Molecular Urology and Genetics of Human Reproduction, Department of Urology, Ioannina University School of Medicine, Ioannina, Greece
5 MFC Clinic, Yonago, Japan
6 Department of Obstetrics and Gynecology, Aristotle University School of Medicine, Thessaloniki, Greece and
7 Department of Urology, Thessalia University School of Medicine, Larissa, Greece

* To whom correspondence should be addressed.
N. Sofikitis, E-mail: akrosnin{at}hotmail.com


  Abstract

Induction of meiotic and post-meiotic alterations of male germ cells in vitro has been the target of several research efforts since 1960. However, to date, the establishment of an ideal culture system in which spermatogonial stem cells can be maintained and directed to proliferate and undergo meiosis and complete spermiogenesis does not exist. This is attributed to the difficulties concerning the isolation and purification of defined subpopulations of germ cells and the establishment of male germ cell lines. In addition, there is no adequate knowledge regarding the optimal biochemical conditions that promote the survival and differentiation of germ cells in long-term cultures. This review focuses on the methodologies that have been proved sufficient to achieve differentiation of cultured male germ cells. Furthermore, the factors regulating spermatogenesis and the technical prerequisites to achieve differentiation of cultured male germ cells are described. Finally, the role of in vitro cultures of immature diploid germ cells in the therapeutic management of men negative for haploid cells in their testes and the subsequent potential genetic and epigenetic risks are discussed.

Keywords: artificial testis; in vitro culture system; meiotic maturation; spermatogonial stem cell.
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