Abstract
BackgroundLeptin 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.MethodsWe 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.ResultsTestosterone 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.ConclusionsThe 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.
Highlights
Leptin plays an important role in reproductive function, and the mechanism of this phenomenon primarily focuses on the hypothalamic–pituitary–gonadal axis
monosodium glutamate (MSG) treatment augmented the weight of body fat and induced hyperleptinemia mice in a time-dependent manner To study the effects of hyperleptinemia and the time course of this effect in the mouse testes, male offspring were injected ip with MSG every day from d0 to d14, d28, or d56 (14MSG, 28MSG, and 56MSG groups, respectively)
The withdrawal of MSG treatment led to the partial recovery of testicular structure and function, which demonstrated that the effects of leptin could be at least partly reversed
Summary
Leptin plays an important role in reproductive function, and the mechanism of this phenomenon primarily focuses on the hypothalamic–pituitary–gonadal axis. Until now, the direct effects of leptin on the testes during development from infancy to adulthood remained unclear. Studies of obese individuals with high levels of leptin suggest that hyperleptinemia is related to the body fat [2]. Leptin, which is the product of the obese (ob) gene, is produced primarily by adipose tissue and plays a pivotal role in the control of food intake and energy expenditure [5]. The effects of leptin are mediated by its specific receptor (LEPR) in target tissues. Giovambattista et al reported that leptin plays an inhibitory role in reproductive functions [9]. The relation between leptin and reproduction is a cause for concern
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