Purpose

Prostate cancer is a major cause of cancer-related death in males worldwide and, in addition to impairing prostate function, also causes testicular adaptations. In this study, we aim to investigate the preventive effect of exercise training on PCa-induced testicular dysfunction.

Methods

As a model, we used fifty Wistar Unilever male rats, randomly divided in four experimental groups. Prostate cancer was chemically and hormonally induced in two groups of animals (PCa groups). One control group and one PCa group was submitted to moderate intensity treadmill exercise training. Fifty weeks after the start of the training the animals were sacrificed and sperm, prostate, testis and serum were collected and analyzed. Sperm concentration and morphology, and testosterone serum levels were determined. In addition, histological analyses of the testes were performed, and testis proteomes and metabolomes were characterized.

Results

We found that prostate cancer negatively affected testicular function, manifested as an arrest of spermatogenesis. Oxidative stress-induced DNA damage, arising from reduced testis blood flow, may also contribute to apoptosis of germ cells and consequential spermatogenic impairment. Decreased utilization of the glycolytic pathway, increased metabolism of ketone bodies and the accumulation of branched chain amino acids were also evident in the PCa animals. Conversely, we found that the treadmill training regimen activated DNA repair mechanisms and counteracted several metabolic alterations caused by PCa without impact on oxidative stress.

Conclusions

These findings confirm a negative impact of prostate cancer on testis function and suggest a beneficial role for exercise training in the prevention of prostate cancer-induced testis dysfunction.

中文翻译：

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慢性运动训练减弱前列腺癌诱导的睾丸分子重塑

目的

前列腺癌是全球男性癌症相关死亡的主要原因，除了损害前列腺功能外，还会导致睾丸适应。在本研究中，我们旨在探讨运动训练对 PCa 诱发的睾丸功能障碍的预防作用。

方法

作为模型，我们使用了 50 只 Wistar Unilever 雄性大鼠，随机分为四个实验组。在两组动物（PCa 组）中化学和激素诱导前列腺癌。一个对照组和一个 PCa 组接受中等强度的跑步机运动训练。训练开始五十周后，处死动物，收集并分析精子、前列腺、睾丸和血清。测定精子浓度和形态以及睾酮血清水平。此外，还对睾丸进行了组织学分析，并对睾丸蛋白质组和代谢组进行了表征。

结果

我们发现前列腺癌对睾丸功能产生负面影响，表现为精子发生停滞。由睾丸血流量减少引起的氧化应激诱导的 DNA 损伤也可能导致生殖细胞凋亡和随之而来的生精障碍。在 PCa 动物中，糖酵解途径的利用率降低、酮体代谢增加和支链氨基酸的积累也很明显。相反，我们发现跑步机训练方案激活了 DNA 修复机制并抵消了 PCa 引起的几种代谢改变，而不影响氧化应激。

结论

这些发现证实了前列腺癌对睾丸功能的负面影响，并表明运动训练在预防前列腺癌引起的睾丸功能障碍方面具有有益作用。