可乐与无糖可乐对雄性小鼠青春期发育提前的影响

Effects of cola and diet cola on the advancement of pubertal development in male mice

  • 摘要:
    摘要:背景 在世界范围内,儿童青少年的青春期启动有提前的趋势,不良膳食如含糖饮料过量摄入可能是导致这一现象的诱因。目的 探讨生命早期可乐和无糖可乐暴露对雄性小鼠青春期启动的影响。方法 雌性C57BL/6J小鼠在检出阴道栓当天开始接受可乐和无糖可乐暴露,暴露一直持续至子代雄性小鼠青春期启动指标出现。其间子代小鼠定期称重,监测子代小鼠每日饮水和摄食量,在青春期启动指标出现当天处死小鼠,收集血清、睾丸、下丘脑组织,检测激素水平和调控青春期启动的关键基因表达水平。结果 与对照组相比,可乐组(P<0.05)和无糖可乐组(P<0.05)小鼠体重均增加,饮水量增加,摄食量减少,并且无糖可乐组小鼠的饮水增加量和摄食减少量均低于可乐组。与对照组相比,可乐组(P<0.01)和无糖可乐组(P<0.01)阴茎剥离时间均提前,可乐组睾丸器官系数升高(P<0.01),生精小管上皮厚度增加(P<0.01),无糖可乐组睾丸器官系数无明显差异,生精小管上皮厚度增加(P<0.05)。与对照组相比,可乐组和无糖可乐组血清激素GnRH(P<0.05)、LH(P<0.05)和FSH(P<0.01)水平均提高。机制方面,与对照组相比,可乐组和无糖可乐组小鼠下丘脑HPG轴中青春期启动相关基因 TTF-1、KISS-1、GPR54、GnRH 的 mRNA 表达水平均增加(P<0.05),能量代谢相关基因 POMC 的mRNA表达水平均降低(P<0.01);睾丸组织中Cyp1b1的mRNA表达水平均降低(P<0.05),Cyp19a1无明显变化。结论 生命早期可乐和无糖可乐暴露可能通过调节雄性小鼠HPG轴上游基因TTF-1,影响HPG轴中KISS-1、GPR54和GnRH基因的表达来促进GnRH、LH和FSH激素的分泌,进而调控睾丸中Cyp1b1基因的表达,导致青春期启动提前。

     

    Abstract: Abstract: Background There is a tendency for early onset of puberty in children and adolescents worldwidely. And excessive consumption of unhealthy diets such as sugary drinks may be a contributing factor.Objective To investigate the effects of early life cola and diet cola exposure on the initiation of puberty in male mice.Methods Female C57BL/6J mice were exposed to cola and diet cola on the day of detection of vaginal plugs, and the exposure continued until the onset of puberty in male offspring mice, during which time the offspring were weighed regularly, and their daily water intake and food intake were monitored. On the day of puberty initiation indexes appeared, the mice were executed, and serum, testis, and hypothalamus tissues were collected to examine the levels of hormones and expression of genes critical to the regulation of the puberty onset.Results Compared with the control group, mice in the cola group (P < 0.05) and the diet cola group (P < 0.05) had a significant increase in body weight, an increase in water intake, and a decrease in food intake, and both the increase in water intake and the decrease in food intake of mice in the diet cola group were lower than those in the cola group. Compared with the control group, the time of penile peeling was significantly earlier in the cola group (P < 0.01) and the diet cola group (P < 0.01). The testicular organ coefficient was significantly higher (P < 0.01), and spermatogenic tubule epithelial thickness was significantly increased (P < 0.01) in the cola group, while there was no significant difference in testicular organ coefficient, and spermatogenic tubule epithelial thickness was significantly increased (P < 0.05) in the diet cola group. Serum hormone levels of GnRH (P < 0.05), LH (P < 0.05), and FSH (P < 0.01) were significantly higher in the cola and diet cola groups compared to the control group. For mechanisms, mRNA expression levels of HPG axisrelated genes TTF-1, KISS-1, GPR54, and GnRH were significantly upregulated in the hypothalamic tissues of mice in the cola group and the diet cola group (P < 0.05), and the mRNA expression levels of energy metabolism-related genes POMC were significantly downregulated (P < 0.01). In testicular tissues, Cyp1b1 mRNA expression was significantly decreased (P < 0.05), whereas no significant changes were observed for Cyp19a1. Conclusion Early-life cola and diet cola exposure may promote secretion of the hormones GnRH, LH, and FSH by modulating the upstream gene TTF-1 of the HPG axis in male mice, affecting the expression of the KISS-1, GPR54, and GnRH genes in the HPG axis, which in turn modulates the expression of the Cyp1b1 gene in the testes, resulting in an earlier initiation of puberty.

     

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