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J Urol. 2015 Aug;194(2):585-91. doi: 10.1016/j.juro.2015.01.099. Epub 2015 Feb 2.

Human Fetal Testicular Tissue Xenotransplantation: A Platform to Study the Effect of Gonadotropins on Human Germ Cell Development In Utero.

Author information

1
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: klo@mtsinai.on.ca.
2
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
3
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
4
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
5
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Physiology and Experimental Medicine Research Program, Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract

PURPOSE:

We examined the effects of long-term hCG stimulation on germ cell maturation, and Sertoli and Leydig cell function in a xenotransplantation model of the human fetal testis.

MATERIALS AND METHODS:

A total of 20 human fetal testes were ectopically xenografted on 20 castrated NCr male nude mice. Grafts were collected for analysis 24 weeks later. Mice were treated with saline as the control or with hCG beginning 4 weeks after the grafts were transplanted.

RESULTS:

Of the grafts 65% survived at 24 weeks. In contrast to untreated pregrafted samples, hCG stimulated xenografts showed significantly increased density of seminiferous tubule formation with Sertoli cell migration to the basement membrane. Germ cell proliferation and differentiation from gonocytes (M2A(+)) to prespermatogonia (MAGE-4A(+)) were observed in graft samples recovered from the hCG and nonhCG treated groups at 24 weeks of treatment. Leydig cells in hCG treated grafts produced significantly more testosterone than nonhCG treated grafts. Although further studies are required to investigate the potential for further differentiation and maturation of xenografted human fetal testes, normal in utero testicular development was reproduced under long-term hCG stimulation.

CONCLUSIONS:

This model represents a means to study long-term effects of gonadotoxins or hormonal stimulation on the maturation of human fetal testes.

KEYWORDS:

animal; fetal organ maturity; gonadotropins; models; seminiferous tubules; testis

PMID:
25656291
DOI:
10.1016/j.juro.2015.01.099
[Indexed for MEDLINE]

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