Claudin-11 Is Over-Expressed and Dislocated From the Blood-Testis Barrier in Sertoli Cells Associated With Testicular Intraepithelial Neoplasia in Men

Histochem Cell Biol. 2009 Jun;131(6):755-64. doi: 10.1007/s00418-009-0576-2. Epub 2009 Feb 25.

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.

MeSH terms

  • Adult
  • Blood-Testis Barrier / cytology
  • Blood-Testis Barrier / metabolism*
  • Claudins
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Microscopy, Immunoelectron
  • Middle Aged
  • Nerve Tissue Proteins / metabolism*
  • Phosphoproteins / metabolism
  • Seminiferous Epithelium / cytology
  • Seminiferous Epithelium / metabolism*
  • Seminiferous Epithelium / ultrastructure
  • Seminiferous Tubules / cytology
  • Seminiferous Tubules / metabolism*
  • Seminiferous Tubules / ultrastructure
  • Sertoli Cells / cytology
  • Sertoli Cells / metabolism*
  • Spermatogenesis / physiology
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / ultrastructure
  • Testis / cytology
  • Testis / metabolism
  • Testis / ultrastructure
  • Up-Regulation
  • Zonula Occludens-1 Protein

Substances

  • CLDN11 protein, human
  • Claudins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • TJP1 protein, human
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein