Involvement of Tumor Necrosis Factor-α in the Pathogenesis of Autoimmune Orchitis in Rats1
Open Access
- 1 June 2003
- journal article
- Published by Oxford University Press (OUP) in Biology of Reproduction
- Vol. 68 (6), 2114-2121
- https://doi.org/10.1095/biolreprod.102.011189
Abstract
We studied the testicular macrophages of rats with experimental autoimmune orchitis (EAO) and analyzed whether the tumor necrosis factor-α (TNFα) is involved in germ cell apoptosis and in Leydig cell steroidogenesis. The EAO was induced in adult male Sprague-Dawley rats by active immunization with testicular homogenate and adjuvants. In the experimental group, a severe orchitis was observed 80 days after the first immunization. ED1- and ED2-positive macrophages were quantified by immunohistochemistry. The TNFα concentration of conditioned media from testicular macrophages (TMCM) was determined by ELISA. The number of apoptotic TNF receptor 1 (TNFR1)-positive germ cells was identified by combining in situ end labeling of apoptotic DNA and immunohistochemical techniques. The effect of TNFα on Leydig cell testosterone production was determined by RIA. In rats with EAO, we observed a significant increase in the number of TNFα-positive testicular macrophages, the TNFα concentration in TMCM, and the number of TNFR1-positive germ cells. Sixty percent of TNFR1-positive germ cells were apoptotic. These results suggest that TNFα could be involved in the pathogenesis of EAO. Acting together with other local factors such as Fas-FasL, TNFα could trigger germ cell apoptosis. We also demonstrated that TNFα inhibited in vitro testosterone production in basal and hCG-stimulated Leydig cells from rats with orchitis.Keywords
This publication has 30 references indexed in Scilit:
- Differential transport of rat and human interleukin-1α across the blood–brain barrier and blood–testis barrier in ratsBrain Research, 2000
- Cytokine Secretion by Macrophages in the Rat Testis1Biology of Reproduction, 1995
- Leukocyte Populations of the Adult Rat Testis Following Removal of the Leydig Cells by Treatment With Ethane Dimethane Sulfonate and Subcutaneous Testosterone Implants1Biology of Reproduction, 1994
- The Testicular Effects of Tumor Necrosis FactorAnnals of Surgery, 1990
- An analysis of the role of tumor necrosis factor in the phenotypic expression of actively induced experimental allergic orchitis and experimental allergic encephalomyelitisClinical Immunology and Immunopathology, 1990
- Sequential Study of the Histopathology and Cellular and Humoral Immune Response During the Development of an Autoimmune Orchitis in Wistar RatsAmerican Journal of Reproductive Immunology, 1989
- The rat testis produces large amounts of an interleukin‐1‐like factorInternational Journal of Andrology, 1987
- Testicular Macrophages: Isolation, Characterization and Hormonal ResponsivenessBiology of Reproduction, 1983
- hCG Responsiveness of Purified Leydig Cells from Immature and Mature RatsHormone Research, 1983
- Penetration of the testicular-tubular barrier by horseradish peroxidase induced by adjuvantThe Anatomical Record, 1973