Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process

Reproductive Biology and Endocrinology

Lugang Huang²  Ping Lin¹  Wei Shan²  Li Zeng²  Bo Gao¹  Kai Li¹  Fei Li²  Jie Zhang¹  Jun Li¹  Guizhen Huang²  Miao Yuan² 

[1] Division of Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China;Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, P.R. China

关键词: pSTAT3;    SOCS3;    Testosterone;    Testis;    Leptin;    MSG;   

Others  :  804664
DOI  :  10.1186/1477-7827-12-15

 received in 2013-09-26, accepted in 2014-01-19,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Yuan et al.; licensee BioMed Central Ltd.

【 图 表 】

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