Skip Navigation


Hum. Reprod. Advance Access originally published online on June 25, 2008
Human Reproduction 2008 23(8):1865-1872; doi:10.1093/humrep/den240
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF ) Freely available
Right arrow All Versions of this Article:
23/8/1865    most recent
den240v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Theas, M.S.
Right arrow Articles by Lustig, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Theas, M.S.
Right arrow Articles by Lustig, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 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

Tumour necrosis factor-{alpha} released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis

M.S. Theas1, C. Rival, S. Jarazo-Dietrich, P. Jacobo, V.A. Guazzone and L. Lustig

Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 10, C1121 ABG Buenos Aires, Argentina

1 Correspondence address. Tel:/Fax: +54-11-59509612; E-mail: ciruba14{at}yahoo.com.ar

BACKGROUND: Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying testicular immune and germ cell (GC) interactions. In this model, EAO was induced in rats by immunization with testicular homogenate and adjuvants; Control (C) rats were injected with adjuvants. EAO was characterized by an interstitial infiltrate of lymphomonocytes and seminiferous tubule damage, moderate 50 days (focal orchitis) and severe 80 days after the first immunization (severe orchitis). Based on the previous results showing that the number of macrophages and apoptotic GC expressing tumour necrosis factor (TNF) receptor 1 increased in EAO, we studied the role of macrophages and TNF-{alpha} in GC apoptosis.

METHODS AND RESULTS: Conditioned media of testicular macrophages (CMTM) obtained from rats killed on Days 50 and 80 decreased the viability (MTS, P < 0.01) and induced apoptosis (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling, TUNEL) of GC obtained from EAO but not from non-immunized, N rats (P < 0.001). TNF-{alpha} content (enzyme-linked immunosorbent assay) was significantly higher in the CMTM from EAO versus C rats on Day 80 (P < 0.05). The apoptotic effect of CMTM from Day 80 rats was abrogated by a selective TNF-{alpha} blocker (Etanercept). Moreover, TNF-{alpha} in vitro induced GC apoptosis. TNF-{alpha} expression (by immunofluorescence) was observed in testicular (ED2+) and non-resident (ED1+) macrophages, the percentage of TNF-{alpha}+ macrophages being similar in focal and severe orchitis.

CONCLUSIONS: Results demonstrated that soluble factors released from testicular EAO macrophages induce apoptosis of GC, biased by the local inflammatory environment, and that TNF-{alpha} is a relevant cytokine involved in testicular damage during severe orchitis.

Key words: autoimmune orchitis/testis/macrophages/tumour necrosis factor-{alpha}/apoptosis

Submitted on December 27, 2007; resubmitted on May 21, 2008; accepted on May 28, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.