Document Detail

Adjudin-mediated Sertoli-germ cell junction disassembly affects Sertoli cell barrier function in vitro and in vivo.
MedLine Citation:
PMID:  20713173     Owner:  NLM     Status:  MEDLINE    
Adjudin, an analogue of lonidamine, affects adhesion between Sertoli and most germ cells, resulting in reversible infertility in rats, rabbits and dogs. Previous studies have described the apical ectoplasmic specialization, a hybrid-type of Sertoli cell-elongating/elongated spermatid adhesive junction, as a key target of adjudin. In this study, we ask if the function of the blood-testis barrier which is constituted by co-existing tight junctions, desmosome-gap junctions and basal ectoplasmic specializations can be maintained when the seminiferous epithelium is under assault by adjudin. We report herein that administration of a single oral dose of adjudin to adult rats increased the levels of several tight junction and basal ectoplasmic specialization proteins during germ cell loss from the seminiferous epithelium. These findings were corroborated by a functional in vitro experiment when Sertoli cells were cultured on Matrigel™-coated bicameral units in the presence of adjudin and transepithelial electrical resistance was quantified across the epithelium. Indeed, the Sertoli cell permeability barrier was shown to become tighter after adjudin treatment as evidenced by an increase in transepithelial electrical resistance. Equally important, the blood-testis barrier in adjudin-treated rats was shown to be intact 2 weeks post-treatment when its integrity was monitored following vascular administration of inulin-fluorescein isothiocyanate which failed to permeate past the barrier and enter into the adluminal compartment. These results illustrate that a unique mechanism exists to maintain blood-testis barrier integrity at all costs, irrespective of the presence of germ cells in the seminiferous epithelium of the testis.
Linlin Su; C Yan Cheng; Dolores D Mruk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-14
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  42     ISSN:  1878-5875     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2011-01-18     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1864-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
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MeSH Terms
Blood-Testis Barrier / drug effects,  metabolism
Cell Proliferation / drug effects
Cells, Cultured
Hydrazines / pharmacology*
Indazoles / pharmacology*
Microscopy, Fluorescence
Rats, Sprague-Dawley
Seminiferous Epithelium / cytology,  drug effects,  metabolism
Sertoli Cells / cytology*,  drug effects*,  metabolism
Tight Junctions / drug effects,  metabolism
Grant Support
R01 HD056034/HD/NICHD NIH HHS; R01 HD056034/HD/NICHD NIH HHS; R01 HD056034-02/HD/NICHD NIH HHS; R01 HD056034-03/HD/NICHD NIH HHS; R03 HD061401/HD/NICHD NIH HHS; R03 HD061401-02/HD/NICHD NIH HHS; U54 HD029990/HD/NICHD NIH HHS
Reg. No./Substance:
0/1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; 0/Hydrazines; 0/Indazoles

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