Chronic exercise training attenuates prostate cancer-induced molecular remodelling in the testis
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ORIGINAL PAPER
Chronic exercise training attenuates prostate cancer-induced molecular remodelling in the testis Bárbara Matos 1 & Daniela Patrício 1 & Magda C. Henriques 1 & Maria J. Freitas 1 & Rui Vitorino 1 & Iola F. Duarte 2 & John Howl 3 & Paula A. Oliveira 4 & Fernanda Seixas 5 & José A. Duarte 6 & Rita Ferreira 7 & Margarida Fardilha 1 Accepted: 30 September 2020 # International Society for Cellular Oncology 2020
Abstract 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 PCainduced 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. Keywords Prostate cancer . Exercise training . Testicular function . Oxidative stress . DNA repair . Metabolism
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00567-9) contains supplementary material, which is available to authorized users. * Margarida Fardilha [email protected] 1
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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 Molecular Pharmacology Group, Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1LY, UK
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Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Universit
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