Overweight and obese men face numerous health problems, including type 2 diabetes, subfertility, and even infertility. However, few studies have focused on the effects of nutritional status and obesity-related regulatory signals on fertility deficiency. Our previous observations have shown that the elevation of plasma 5'-adenosine monophosphate (5'-AMP) and the accumulation of adenosine in liver and muscle of obese diabetic db/db mice are related to insulin resistance. Here, we found that adenosine accumulation in testis is a common marker of both genetic obesity and high-fat-diet induced obese mice. An messenger RNA sequencing analysis indicated that 78 upregulated genes and 155 downregulated genes in the testis of 5'-AMP-treated mice overlapped with the same genes in the testis of ob/ob mice, and these genes belonged to the clusters of steroid metabolic process and regulation of hormone levels, respectively. Serum testosterone was reduced in ob/ob and 5'-AMP-treated mice. Metabolomic analysis based on 1 H nuclear magnetic resonance showed that the testicular metabolic profiles of ob/ob mice were similar to those of 5'-AMP treated mice. Exogenous 5'-AMP inhibited the phosphorylation of AKT and mammalian target of rapamycin signal transduction and reduced the proliferating cell nuclear antigen expressions in testes. Our results suggest that the accumulation of adenosine causes metabolic disorders in testes and associates lower testosterone level in obese mice.

中文翻译：

---

腺苷积累会导致睾丸代谢紊乱，并与肥胖小鼠睾丸激素水平降低有关。

超重和肥胖的男性面临许多健康问题，包括2型糖尿病，不育症甚至不育症。但是，很少有研究关注营养状况和肥胖相关的调节信号对生育力缺乏的影响。我们以前的观察结果表明，肥胖的db / db小鼠血浆5'-腺苷一磷酸（5'-AMP）升高和腺苷在肝脏和肌肉中的蓄积与胰岛素抵抗有关。在这里，我们发现腺苷在睾丸中的积累是遗传性肥胖和高脂饮食诱导的肥胖小鼠的共同标志。信使RNA测序分析表明，经5'-AMP处理的小鼠睾丸中有78个上调基因和155个下调基因与ob / ob小鼠睾丸中的相同基因重叠，这些基因分别属于类固醇代谢过程和激素水平调控的簇。ob / ob和5'-AMP处理的小鼠的血清睾丸激素降低。基于1 H核磁共振的代谢组学分析表明，ob / ob小鼠的睾丸代谢谱与5'-AMP处理的小鼠相似。外源5'-AMP抑制AKT的磷酸化和雷帕霉素信号转导的哺乳动物目标，并降低了睾丸中增殖细胞核抗原的表达。我们的结果表明，腺苷的积累会引起睾丸代谢紊乱，并导致肥胖小鼠睾丸激素水平降低。基于1 H核磁共振的代谢组学分析表明，ob / ob小鼠的睾丸代谢谱与5'-AMP处理的小鼠相似。外源5'-AMP抑制AKT的磷酸化和雷帕霉素信号转导的哺乳动物目标，并降低了睾丸中增殖细胞核抗原的表达。我们的结果表明，腺苷的积累会导致睾丸代谢紊乱，并导致肥胖小鼠睾丸激素水平降低。基于1 H核磁共振的代谢组学分析表明，ob / ob小鼠的睾丸代谢谱与5'-AMP处理的小鼠相似。外源5'-AMP抑制AKT的磷酸化和雷帕霉素信号转导的哺乳动物目标，并降低了睾丸中增殖细胞核抗原的表达。我们的结果表明，腺苷的积累会导致睾丸代谢紊乱，并导致肥胖小鼠睾丸激素水平降低。