title: Protective Effects of Fluvastatin on Reproductive Function in Obese Male Rats Induced by High-Fat Diet through Enhanced Signaling of mTOR.
abstract: BACKGROUND
  Statins can reduce reproductive damage induced by obesity or high-fat diet (HFD), but the specific regulatory mechanisms are largely unknown. Since mTOR/p70s6k sinaling promotes spermatogonia proliferation and spermatogenesis, we hypothesized that this pathway will be involved in the protective effects of statin in HFD-induced reproductive dysfunction.
  
  
  METHODS
  Male Sprague Dawley rats (3 weeks old) were randomly divided into a control group (standard diet), HFD group, and a fluvastatin group (HFD + fluvastatin at 6mg/kg, once daily by oral gavage). After 8 weeks, body weight was obtain and rats were sacrificed. Weights of the testes, gross morphology, sperm parameters, circulating levels of sex hormones, lipid levels, and tissue mTOR, p-P70s6k were measured. Another set of male rats were treated with rapamycin or vehicle. Flow cytometry was used to detect the spermatogonia marker c-kit and cell cycle. p-P70s6k expression was analyzed by Western blot.
  
  
  RESULTS
  HFD not only results in rat obesity but also leads to spermatogenetic damage and fluvastatin was able to partially block the effects of HFD. Fluvastatin also partially reversed the suppression of mTOR and p-p70s6k expresson.
  
  
  CONCLUSIONS
  Our data suggest that fluvastatin has protective effects on reproductive function in obese male rats most probably through enhanced signaling of mTOR.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Cui
authors.forename: Chunlan
authors.initials: C
authors.lastname: Long
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004958:Estradiol / Q000032:analysis; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D007211:Indoles / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D020011:Protective Agents / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000032:analysis
chemical_list: D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D020011:Protective Agents; D013739:Testosterone; D000077340:Fluvastatin; D004958:Estradiol; D007986:Luteinizing Hormone; D019009:Proto-Oncogene Proteins c-kit; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: Fluvastatin; Obesity; Proliferation; Spermatogenesis; mTOR