Altered expression of ZO-1 and ZO-2 in Sertoli cells and loss of blood-testis barrier integrity in testicular carcinoma in situ.
Carcinoma in situ (CIS) is the noninvasive precursor of most human testicular germ cell tumors. In normal seminiferous epithelium, specialized tight junctions between Sertoli cells constitute the major component of the blood-testis barrier. Sertoli cells associated with CIS exhibit impaired maturation status, but their functional significance remains unknown. The aim was to determine whether the blood-testis barrier is morphologically and/or functionally altered. We investigated the expression and distribution pattern of the tight junction proteins zonula occludens (ZO) 1 and 2 in normal seminiferous tubules compared to tubules showing CIS. In normal tubules, ZO-1 and ZO-2 immunostaining was observed at the blood-testis barrier region of adjacent Sertoli cells. Within CIS tubules, ZO-1 and ZO-2 immunoreactivity was reduced at the blood-testis barrier region, but spread to stain the Sertoli cell cytoplasm. Western blot analysis confirmed ZO-1 and ZO-2, and their respective mRNA were shown by RT-PCR. Additionally, we assessed the functional integrity of the blood-testis barrier by lanthanum tracer study. Lanthanum permeated tight junctions in CIS tubules, indicating disruption of the blood-testis barrier. In conclusion, Sertoli cells associated with CIS show an altered distribution of ZO-1 and ZO-2 and lose their blood-testis barrier function.
Fink
Cornelia
C
Institute of Veterinary Anatomy, Histology, and Embryology, University of Giessen, Giessen, Germany. cornelia.fink@vetmed.uni-giessen.de
Weigel
Roswitha
R
Hembes
Tanja
T
Lauke-Wettwer
Heidrun
H
Kliesch
Sabine
S
Bergmann
Martin
M
Brehm
Ralph H
RH
D000328:Adult; D001814:Blood-Testis Barrier / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism* / Q000648:ultrastructure; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein