title: Nuclear factor E2-related factor-2 (Nrf2) expression and regulation in male reproductive tract.
abstract: BACKGROUND
  Nuclear factor E2-related factor-2 (Nrf2, Nfe2l2) plays an important, protective role in many tissues. However, information on molecular mechanisms of detoxification and drug metabolism regulated by Nrf2/NRF2 in testis and epididymis is scarce, but it may help to better characterize the function of blood-testis and epididymis barriers.
  
  
  METHODS
  Constitutive gene expression was analyzed by real time PCR with TaqMan Assay using ΔCT-method. Additionally, gene expression after treatment with oltipraz- specific Nrf2 inducer was evaluated using ΔΔCT-method. Cellular localization of the Nrf2 was visualized by immunohistochemical reaction.
  
  
  RESULTS
  The study showed that Nrf2 mRNA level in rat epididymis was higher than in testis. In human tissues, both testis and epididymis demonstrated similar expression levels of NRF2. Immunohistochemical analysis revealed NRF2/Nrf2 protein expression in testis and epididymis, which in the case of testis was dependant on spermatogenesis stage. Both in human and rat tissues constitutive expression of NQO1/Nqo1 was slightly higher in epididymis than in testis. Other Nrf2 regulated genes: GCLC/Gclc and UGT1A6/Ugt1a6 showed different ratios of testis/epididymis/liver expression levels. Treatment with oltipraz (Nrf2 inducer) resulted in significant induction of Nrf2 expression solely in corpus of epididymis.
  
  
  CONCLUSIONS
  Components of the Nrf2/NRF2 system along with coordinated genes are expressed in testis and epididymis. Moreover, some interspecies differences between rat and human were observed, which may impact extrapolation of experimental data into clinical findings. Studies on animal model showed that corpus of epididymis is the most responsive part of the male reproductive tract to oltipraz exposure at the gene expression level.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wajda
authors.affiliation: Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Łapczuk
authors.affiliation: Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Grabowska
authors.affiliation: Department of Urology and Urological Oncology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Słojewski
authors.affiliation: Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Laszczyńska
authors.affiliation: Department of Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Urasińska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland. Electronic address: marek.drozdzik@pum.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Droździk
mesh_terms: D000368:Aged; D000818:Animals; D004822:Epididymis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013737:Testis / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat
keywords: Male reproductive system; Nuclear factor E2-related factor-2