title: Changes in Inflammatory Cytokines Accompany Deregulation of Claudin-11, Resulting in Inter-Sertoli Tight Junctions in Varicocele Rat Testes.
abstract: OBJECTIVE
  To elucidate the changes that occur in the blood-testis barrier during varicocele we examined changes in Cldn11 (claudin-11), an element of the blood-testis barrier, as well as steroidogenesis and proinflammatory cytokines in a model of varicocele rat testes.
  
  
  METHODS
  Male rats with experimentally induced varicocele were sacrificed 4 weeks after operation. Testicular histology and blood testosterone concentrations were examined. The expression of tight junctions, steroidogenic enzymes, apoptosis and immune cell markers, and proinflammatory cytokines in the testes were evaluated by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry.
  
  
  RESULTS
  Weight and Johnsen scores of varicocele testes were lower than those of normal testes. mRNA expression of Bad and Bax increased whereas Bcl-xl and Bcl2 mRNA decreased in varicocele testes compared to controls. Although blood testosterone did not change, Leydig cell 3βHsd immunoreactivity, testicular 3βHsd6 and 17βHsd3 mRNA were significantly decreased in varicocele testes. Cldn11 mRNA and protein levels in varicocele testes were higher than in normal testes together with altered expression of Ocln, Zo1 and N-cadherin mRNA. Cldn11 immunoreactivity appeared as wavy strands at the periphery of the seminiferous epithelium in normal testes but was frequently found in the Sertoli cell cytoplasm in varicocele testes. In varicocele testes Tnfα, Il1α, Il6, Cd45, Cd3g and Cd3d mRNA was increased.
  
  
  CONCLUSIONS
  An increase in proinflammatory cytokines might be responsible for deregulation of Cldn11 in the Sertoli cells in varicocele testes, leading to alterations in the permeability of the blood-testis barrier and immunological barriers to normal spermatogenesis.
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Department of Urology, Chonbuk National University Medical School (JKP), Jeonju, Republic of Korea.
authors.forename: Yeong Seok
authors.initials: YS
authors.lastname: Oh
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Department of Urology, Chonbuk National University Medical School (JKP), Jeonju, Republic of Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Jo
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Department of Urology, Chonbuk National University Medical School (JKP), Jeonju, Republic of Korea. Electronic address: rain@chonbuk.ac.kr.
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Department of Urology, Chonbuk National University Medical School (JKP), Jeonju, Republic of Korea. Electronic address: mcgye@hanyang.ac.kr.
authors.forename: Myung Chan
authors.initials: MC
authors.lastname: Gye
mesh_terms: D000818:Animals; D015153:Blotting, Western; D057167:Claudins / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D012313:RNA / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism* / Q000473:pathology; D013091:Spermatogenesis / Q000235:genetics*; D019108:Tight Junctions; D014646:Varicocele / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D057167:Claudins; C492353:Cldn11 protein, rat; D016207:Cytokines; D012313:RNA
keywords: CLDN11 protein, rat; blood-testis barrier; spermatogenesis; testis; varicocele