Sertoli Cell-Specific Deletion of the Androgen Receptor Compromises Testicular Immune Privilege in Mice1
Open Access
- 1 August 2011
- journal article
- Published by Oxford University Press (OUP) in Biology of Reproduction
- Vol. 85 (2), 254-260
- https://doi.org/10.1095/biolreprod.110.090621
Abstract
In the mammalian testis, meiotic and postmeiotic germ cell antigens are granted immune privilege. Both local immune suppression and specialized intercellular junctions between somatic Sertoli cells have been proposed to contribute to a highly restricted and effective blood-testis barrier (BTB) that helps maintain tolerance to germ cell antigens. Several studies have suggested that androgens play a role in immune suppression, although direct evidence for this is lacking. We previously reported that Sertoli cell-specific ablation of the androgen receptor (Ar) decreases expression of Cldn3, an androgen-regulated gene and component of Sertoli cell tight junctions, and increases the permeability of the BTB to biotin, a small-molecular-weight tracer. The physiological consequences of Sertoli cell-specific Ar (S-Ar) ablation on immune privilege are unknown. Here we show that in the testes of S-Ar mutant mice, the ultrastructure of Sertoli cell tight junctions is defective and testicular IgG levels are elevated. The interstitium of S-Ar mutant testes becomes populated with macrophages, neutrophils, plasma cells, and eosinophils, and serum samples of mutant mice contain antibodies against germ cell antigens. Together, these results suggest that Sertoli cell-specific deletion of the androgen receptor results in loss of testicular immune privilege. Suppressed levels of androgen signaling may be a contributing factor in idiopathic male infertility.Keywords
This publication has 41 references indexed in Scilit:
- Selective Ablation of the Androgen Receptor in Mouse Sertoli Cells Affects Sertoli Cell Maturation, Barrier Formation and Cytoskeletal DevelopmentPLOS ONE, 2010
- Tight junctions in the testis: new perspectivesPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2010
- Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal womenJournal of Endocrinology, 2010
- Gonadotropins Regulate Rat Testicular Tight Junctions in VivoEndocrinology, 2010
- Claudin 11 Deficiency in Mice Results in Loss of the Sertoli Cell Epithelial Phenotype in the Testis1Biology of Reproduction, 2010
- Claudin 5 Expression in Mouse Seminiferous Epithelium Is Dependent upon the Transcription Factor Ets Variant 5 and Contributes to Blood-Testis Barrier Function1Biology of Reproduction, 2009
- Estrogen and testosterone therapies in multiple sclerosisPublished by Elsevier BV ,2009
- Androgens in rheumatoid arthritis: when are they effectors?Arthritis Research & Therapy, 2009
- ETV5 Is Required for Continuous Spermatogenesis in Adult Mice and May Mediate Blood–Testes Barrier Function and Testicular Immune PrivilegeAnnals of the New York Academy of Sciences, 2007
- 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