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Hum. Reprod. Advance Access published online on August 11, 2008

Human Reproduction, doi:10.1093/humrep/den295
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© The Author 2008. 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@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed: the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given: if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative word this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Germ cell differentiation in the marmoset (Callithrix jacchus) during fetal and neonatal life closely parallels that in the human

R.T. Mitchell1,4, G. Cowan1, K.D. Morris1, R.A. Anderson1, H.M. Fraser1, K.J. Mckenzie2, W.H.B. Wallace3, C.J.H. Kelnar3, P.T.K. Saunders1 and R.M. Sharpe1

1 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK 2 Department of Pathology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, Scotland, UK 3 Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, Scotland, UK

4 Correspondence address. Fax: +44-131-242-6197; E-mail: r.mitchell{at}hrsu.mrc.ac.uk

BACKGROUND: Testicular germ cell tumours (TGCT) are thought to originate from fetal germ cells that fail to differentiate normally, but no animal model for these events has been described. We evaluated the marmoset (Callithrix jacchus) as a model by comparing perinatal germ cell differentiation with that in humans.

METHODS: Immunohistochemical profiling was used to investigate germ cell differentiation (OCT4, NANOG, AP-2{gamma}, MAGE-A4, VASA, NANOS-1) and proliferation (Ki67) in fetal and neonatal marmoset testes in comparison with the human and, to a lesser extent, the rat.

RESULTS: In marmosets and humans, differentiation of gonocytes into spermatogonia is associated with the gradual loss of pluripotency markers such as OCT4 and NANOG, and the expression of germ cell-specific proteins such as VASA. This differentiation occurs asynchronously within individual cords during fetal and early postnatal life. This contrasts with rapid and synchronous germ cell differentiation within and between cords in the rat. Similarly, germ cell proliferation in the marmoset and human occurs throughout perinatal life, in contrast to rats in which proliferation ceases during this period.

CONCLUSIONS: The marmoset provides a good model for normal human germ cell differentiation and proliferation. The perinatal marmoset may be a useful model in which to establish factors that lead to failure of normal germ cell differentiation and the origins of TGCT.

Key words: common marmoset/cell differentiation/germ cells/carcinoma in situ/testis


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