title: Studies on the characteristics and mechanisms of testicular toxicity induced by Hydroxyurea.
abstract: OBJECTIVE
  Apoptosis plays a dominant role in both spontaneous spermatogenesis and germ cell death. This study was aimed to investigate the functions of related genes in testicular germ cell death induced by Hydroxyurea (HU).
  
  
  METHODS
  Wild-type (WT) and FasL transgenic (TG) DBA/C57BL mice were intraperitoneal injected with 400 mg/kg HU. Twelve hours later, testes were collected. Histomorphology of testis was observed by staining with Periodic Acid Schiff (PAS). Apoptosis was assessed by TUNEL assay. mRNA and protein levels of related genes were evaluated by quantitative RT-PCR and Western blot, respectively.
  
  
  RESULTS
  The 2 × 2 factorial design comparative experiments between the WT and TG mice showed that the TG mice exhibited a higher basal apoptotic index. The basal mRNA levels of Fas and FasL and protein levels of Fas, FasL, Caspase-3, Caspase-8 and Caspase-9 in the TG mice were also higher than that in the WT mice. Twelve hours after injection of HU, the testicular tubules exhibited no significantly morphological changes but apoptosis index remarkably increased in both the WT and TG mice, with the latter having the higher amplitude. Although, HU up-regulated the mRNA of apoptosis-related genes, such as Fas and FasL, in both the TG and WT mice, the increased amplitude was more obvious in the TG mice. By Western blot analysis, apoptosis-related proteins Fas, FasL Caspase-3, Caspase-8 and Caspase-9 were significantly increased in both the WT and TG mice, with the TG mice exhibiting a greater up-regulation.
  
  
  CONCLUSIONS
  Germ cell apoptosis induced by the HU treatment may be related to the FasL-mediated signal transduction pathway.
authors.affiliation: a National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Department of Pharmacology and Toxicology , Shanghai Institute of Planned Parenthood Research , Shanghai , China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: a National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Department of Pharmacology and Toxicology , Shanghai Institute of Planned Parenthood Research , Shanghai , China.
authors.forename: Chun-qi
authors.initials: CQ
authors.lastname: Wu
authors.affiliation: a National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Department of Pharmacology and Toxicology , Shanghai Institute of Planned Parenthood Research , Shanghai , China.
authors.forename: Yong-wei
authors.initials: YW
authors.lastname: Luo
authors.affiliation: a National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Department of Pharmacology and Toxicology , Shanghai Institute of Planned Parenthood Research , Shanghai , China.
authors.forename: Ming-yang
authors.initials: MY
authors.lastname: Liao
authors.affiliation: a National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Department of Pharmacology and Toxicology , Shanghai Institute of Planned Parenthood Research , Shanghai , China.
authors.forename: Zu-yue
authors.initials: ZY
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D006918:Hydroxyurea / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor; D020169:Caspases; D006918:Hydroxyurea
keywords: Apoptosis; Hydroxyurea; reproductive toxicity; testis