title: Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process.
abstract: BACKGROUND
  Leptin plays an important role in reproductive function, and the mechanism of this phenomenon primarily focuses on the hypothalamic-pituitary-gonadal axis. However, until now, the direct effects of leptin on the testes during development from infancy to adulthood remained unclear. The aim of the present study was to explore the effects and molecular mechanisms that underlie leptin's action in the testes during sexual maturation.
  
  
  METHODS
  We used a monosodium glutamate (MSG)-treated mouse model to assess the effects of endogenous hyperleptinemia on the development of the testes from infancy to adulthood. Then, a variety of reproductive parameters were measured, including the concentration of testosterone, the weight and volume of the testicles, the diameter of the seminiferous tubules, and numbers of spermatogonia, spermatocytes, sperm, Leydig cells and offspring. In addition, we assessed the direct role of leptin and suppressor of cytokine signalling 3 (SOCS3)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3) on the testes in vitro.
  
  
  RESULTS
  Testosterone secretion exhibited a diverse response: a low concentration of leptin induced testosterone secretion, and a high concentration inhibited testosterone secretion both in vivo and in vitro. A variety of reproductive parameters decreased in hyperleptinemic mice, including the weight and volume of the testicles, the diameter of the seminiferous tubules, and the numbers of spermatocytes, sperm, Leydig cells and offspring. The amount of spermatogonia was also elevated. The development of the testes was partially recovered after hyperleptinemia withdrawal. A high concentration of leptin induced SOCS3 expression and inhibited pSTAT3 expression in the testes.
  
  
  CONCLUSIONS
  The results indicated that MSG-induced hyperleptinemia directly affects testicular structure and function and that SOCS3/pSTAT3 played an important role in this process. These results also indicated the importance of monitoring and controlling leptin levels in obese male children. SOCS3 is a potential therapeutic target for leptin-induced dysgenesis.
authors: Miao
authors: M
authors: Yuan
authors: Guizhen
authors: G
authors: Huang
authors: Jun
authors: J
authors: Li
authors: Jie
authors: J
authors: Zhang
authors: Fei
authors: F
authors: Li
authors: Kai
authors: K
authors: Li
authors: Bo
authors: B
authors: Gao
authors: Li
authors: L
authors: Zeng
authors: Wei
authors: W
authors: Shan
authors: Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, P,R, China. linping8@yahoo.com.
authors: Ping
authors: P
authors: Lin
authors: Lugang
authors: L
authors: Huang
mesh_terms: D000818:Animals; D005260:Female; D020738:Leptin / Q000097:blood*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012970:Sodium Glutamate / Q000633:toxicity; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D013737:Testis / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D020738:Leptin; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012970:Sodium Glutamate