title: Claudin-11 is over-expressed and dislocated from the blood-testis barrier in Sertoli cells associated with testicular intraepithelial neoplasia in men.
abstract: In mouse testis, claudin-11 is responsible for the formation of specific parallel TJ strands of the blood-testis barrier (BTB). Concerning the human BTB, there is no information about the transmembrane TJ proteins. We recently demonstrated the loss of functional integrity of the BTB in testicular intraepithelial neoplasia (TIN), associated with a dislocation of the peripheral TJ proteins ZO-1 and ZO-2. Here, we determined the expression and distribution of claudin-11 at the human BTB in seminiferous tubules with normal spermatogenesis (NSP) and TIN. Immunostaining of claudin-11 revealed intense signals at the basal BTB region in seminiferous epithelium with NSP. Within TIN tubules, claudin-11 immunostaining became diffuse and cytoplasmic. Double immunogold labeling demonstrated a co-localization of claudin-11 and ZO-1 at the inter-Sertoli cell junctions. Real-time RT-PCR of laser microdissected tubules showed an up-regulation of claudin-11 mRNA in TIN. Additionally, increased claudin-11 protein was observed by Western blot. We conclude that claudin-11 constitutes a TJ protein at the human BTB. In TIN tubules, claudin-11 is up-regulated and dislocated from the BTB. Therefore, the disruption of the BTB is related to a dysfunction of claudin-11 and not to a failure of its expression.
authors.affiliation: Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Frankfurter Str. 98, 35392 Giessen, Germany. Cornelia.Fink@vetmed.uni-giessen.de
authors.forename: Cornelia
authors.initials: C
authors.lastname: Fink
authors.forename: Roswitha
authors.initials: R
authors.lastname: Weigel
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.forename: Jochen
authors.initials: J
authors.lastname: Wilhelm
authors.forename: Sabine
authors.initials: S
authors.lastname: Kliesch
authors.forename: Martina
authors.initials: M
authors.lastname: Zeiler
authors.forename: Martin
authors.initials: M
authors.lastname: Bergmann
authors.forename: Ralph
authors.initials: R
authors.lastname: Brehm
mesh_terms: D000328:Adult; D001814:Blood-Testis Barrier / Q000166:cytology / Q000378:metabolism*; D057167:Claudins; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D012670:Seminiferous Epithelium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D012671:Seminiferous Tubules / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013736:Testicular Neoplasms / Q000378:metabolism / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D015854:Up-Regulation; D062826:Zonula Occludens-1 Protein
chemical_list: C120453:CLDN11 protein, human; D057167:Claudins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein