title: Expression and role of leptin under hypoxic conditions in human testis: organotypic in vitro culture experiment and clinical study on patients with varicocele.
abstract: OBJECTIVE
  We investigated the expression and the exact role of leptin under hypoxic conditions in the human testis.
  
  
  METHODS
  Five testes from patients treated with orchiectomy for prostate cancer were used to construct an in vitro hypoxic culture system for human testicular tissue. Immunohistochemistry was performed to analyze leptin protein expression. Leptin, leptin receptor and HIF-1α mRNA were examined by quantitative reverse transcriptase-polymerase chain reaction. Serum and seminal plasma leptin, gonadal hormones and semen parameters were evaluated in 10 healthy donors and 42 infertile patients with varicocele before and after surgery.
  
  
  RESULTS
  The viability of in vitro cultured testicular tissue was well maintained within 48 hours based on the results of morphological analysis, cell number and cell specific mRNAs. Immunohistochemistry demonstrated that leptin was mainly expressed in seminiferous tubules. Interestingly the optical density of leptin, leptin mRNA and HIF-1α mRNA was significantly increased under hypoxia. Leptin mRNA and HIF-1α mRNA correlated positively (Rs = 0.843, p <0.01). In the clinical study the concentration of seminal plasma leptin before varicocelectomy was markedly higher in patients (mean ± SD 3.01 ± 1.23 ng/l, p <0.01). It was highest in the grade 3 group (mean 3.95 ± 1.37 ng/l, p <0.01) and significantly decreased in the 6-month postoperative group (2.35 ± 0.78, p <0.05). Furthermore, negative correlations were observed between seminal plasma leptin and the sperm concentration (Rs = -0.187, p <0.05), and progressive motility (Rs = -0.234, p <0.05).
  
  
  CONCLUSIONS
  Leptin expression was induced under hypoxia in the human testis, probably via the HIF-1α related response pathway. Seminal plasma leptin closely correlated with varicocele related spermatogenesis dysfunction. It might effectively reflect the testicular hypoxic environment.
authors: Department of Urology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Andrology, Shanghai, People's Republic of China; Department of Urology, Pediatric Urology and Andrology, Section Molecular Andrology, Justus Liebig University Giessen, Giessen, Germany.
authors: Kai
authors: K
authors: Ni
authors: Department of Urology, Pediatric Urology and Andrology, Section Molecular Andrology, Justus Liebig University Giessen, Giessen, Germany.
authors: Klaus
authors: K
authors: Steger
authors: Department of Urology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Andrology, Shanghai, People's Republic of China.
authors: Hao
authors: H
authors: Yang
authors: Department of Urology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Andrology, Shanghai, People's Republic of China.
authors: Hongxiang
authors: H
authors: Wang
authors: Department of Urology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Andrology, Shanghai, People's Republic of China.
authors: Kai
authors: K
authors: Hu
authors: Department of Urology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Andrology, Shanghai, People's Republic of China. Electronic address: dr_binchen@126.com.
authors: Bin
authors: B
authors: Chen
mesh_terms: D015687:Cell Hypoxia; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D013737:Testis / Q000378:metabolism*; D014646:Varicocele / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D020738:Leptin
keywords: Hif1a protein; anoxia; human; leptin; testis; varicocele