Matos Bárbara, Patrício Daniela, Henriques Magda C, Freitas Maria J, Vitorino Rui, Duarte Iola F, Howl John, Oliveira Paula A, Seixas Fernanda, Duarte José A, Ferreira Rita, Fardilha Margarida
Institute of Biomedicine - iBiMED, Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal.
CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Cell Oncol (Dordr). 2021 Apr;44(2):311-327. doi: 10.1007/s13402-020-00567-9. Epub 2020 Oct 19.
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.
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.
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.
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.
前列腺癌是全球男性癌症相关死亡的主要原因，除损害前列腺功能外，还会引起睾丸适应性变化。在本研究中，我们旨在探讨运动训练对前列腺癌诱导的睾丸功能障碍的预防作用。
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（前列腺癌组）中通过化学和激素方法诱导前列腺癌。一组对照组和一组前列腺癌组进行中等强度的跑步机运动训练。训练开始50周后，处死动物并收集精子、前列腺、睾丸和血清进行分析。测定精子浓度和形态以及血清睾酮水平。此外，对睾丸进行组织学分析，并对睾丸蛋白质组和代谢组进行表征。
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。睾丸血流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。在前列腺癌动物中还明显出现糖酵解途径利用率降低、酮体代谢增加和支链氨基酸积累。相反，我们发现跑步机训练方案激活了DNA修复机制，并抵消了前列腺癌引起的几种代谢改变，而对氧化应激没有影响。
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诱导的睾丸功能障碍中具有有益作用。
