{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T12:35:27Z","timestamp":1778070927671,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT-Portuguese Foundation of Science and Technology","doi-asserted-by":"publisher","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute for Biomedicine","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}]},{"name":"Institute for Biomedicine","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}]},{"name":"Institute for Biomedicine","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}]},{"name":"Institute for Biomedicine","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}]},{"name":"Institute for Biomedicine","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"Institute for Biomedicine","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}]},{"name":"Institute for Biomedicine","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}]},{"name":"UMIB","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}]},{"name":"UMIB","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}]},{"name":"UMIB","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}]},{"name":"UMIB","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}]},{"name":"UMIB","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"UMIB","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}]},{"name":"UMIB","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}]},{"name":"QOPNA","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}]},{"name":"QOPNA","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}]},{"name":"QOPNA","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}]},{"name":"QOPNA","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}]},{"name":"QOPNA","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"QOPNA","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}]},{"name":"QOPNA","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}]},{"name":"European Investment Funds by FEDER\/COMPETE\/POCI\u2014Operational Competitiveness and Internationalization Program","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["PTDC\/DTP-DES\/6077\/2014"],"award-info":[{"award-number":["PTDC\/DTP-DES\/6077\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["iBiMED; UIDB\/04501\/2020"],"award-info":[{"award-number":["iBiMED; UIDB\/04501\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["PEst-OE\/SAU\/UI0215\/2019"],"award-info":[{"award-number":["PEst-OE\/SAU\/UI0215\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["FCT UID\/QUI\/00062\/2019"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT of the Portuguese Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["SFRH\/BD\/136896\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136896\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging is associated with testicular morphological and functional alterations, but the underlying molecular mechanisms and the impact of physical exercise are poorly understood. In this study, we examined the effects of age and lifelong moderate-intensity exercise on rat testis. Mature adults (35 weeks) and middle-aged (61 weeks) Wistar Unilever male rats were maintained as sedentary or subjected to a lifelong moderate-intensity treadmill training protocol. Testis weight and histology, mitochondrial biogenesis and function, and proteins involved in protein synthesis and stress response were evaluated. Our results illustrate an age-induced testicular atrophy that was associated with alterations in stress response, and mitochondrial biogenesis and function. Aging was associated with increased testicular levels of heat shock protein beta-1 (HSP27) and antioxidant enzymes. Aging was also associated with decreased mRNA abundance of the nuclear respiratory factor 1 (Nrf1), a key transcription factor for mitochondrial biogenesis, which was accompanied by decreased protein levels of the oxidative phosphorylation system (OXPHOS) complexes subunits in the testes of older animals. On the other hand, exercise did not protect against age-induced testicular atrophy and led to deleterious effects on sperm morphology. Exercise led to an even more pronounced decrease in the Nrf1 mRNA levels in testes of both age groups and was associated with decreased mRNA abundance of other mitochondrial biogenesis markers and decreased protein levels of OXPHOS complexes subunits. Lifelong moderate-intensity exercise training was also associated with an increase in testicular oxidative stress markers and possibly with reduced translation. Together, our results indicate that exercise did not protect against age-induced testicular atrophy and was not associated with beneficial changes in mitochondria and stress response, further activating mechanisms of protein synthesis inhibition.<\/jats:p>","DOI":"10.3390\/ijms231911619","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Age and Lifelong Moderate-Intensity Exercise Training on Rats\u2019 Testicular Function"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-3259","authenticated-orcid":false,"given":"Joana V.","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"QOPNA & LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-4739","authenticated-orcid":false,"given":"Joana","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9570-1819","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Matos","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Magda C.","family":"Henriques","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Daniela","family":"Patr\u00edcio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Ana D.","family":"Martins","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-5917","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-4051","authenticated-orcid":false,"given":"Rita","family":"Ferreira","sequence":"additional","affiliation":[{"name":"QOPNA & LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-5699","authenticated-orcid":false,"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"QOPNA & LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-9173","authenticated-orcid":false,"given":"Margarida","family":"Fardilha","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine\u2014iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/14647273.2018.1504325","article-title":"Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility","volume":"23","author":"Heidary","year":"2020","journal-title":"Hum. Fertil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45457","DOI":"10.1038\/srep45457","article-title":"Study on the short-term effects of increased alcohol and cigarette consumption in healthy young men\u2019s seminal quality","volume":"7","author":"Silva","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Silva, J.V., Cabral, M., Correia, B.R., Carvalho, P., Sousa, M., Oliveira, P.F., and Fardilha, M. (2019). mTOR Signaling Pathway Regulates Sperm Quality in Older Men. Cells, 8.","DOI":"10.3390\/cells8060629"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/humrep\/dey357","article-title":"Cytological and molecular aspects of the ageing sperm","volume":"34","author":"Paoli","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/gerona\/gly082","article-title":"Testicular Aging: An Overview of Ultrastructural, Cellular, and Molecular Alterations","volume":"74","author":"Santiago","year":"2019","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00421-018-3989-6","article-title":"Exploring the effect of exercise training on testicular function","volume":"119","author":"Matos","year":"2019","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1177\/1557988316669045","article-title":"The Impact of Intense Exercise on Semen Quality","volume":"11","author":"Rossato","year":"2017","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.fertnstert.2010.11.006","article-title":"Physical activity and semen quality among men attending an infertility clinic","volume":"95","author":"Wise","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1677\/JOE-08-0477","article-title":"The effects of intensive, long-term treadmill running on reproductive hormones, hypothalamus\u2013pituitary\u2013testis axis, and semen quality: A randomized controlled study","volume":"200","author":"Safarinejad","year":"2009","journal-title":"J. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Torma, F., Koltai, E., Nagy, E., Ziaaldini, M.M., Posa, A., Koch, L.G., Britton, S.L., Boldogh, I., and Radak, Z. (2014). Exercise Increases Markers of Spermatogenesis in Rats Selectively Bred for Low Running Capacity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114075"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1007\/s00421-011-2304-6","article-title":"Physically active men show better semen parameters and hormone values than sedentary men","volume":"112","author":"Vaamonde","year":"2012","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/aje\/kwv338","article-title":"Is Sedentary Lifestyle Associated with Testicular Function? A Cross-Sectional Study of 1,210 Men","volume":"184","author":"Priskorn","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.fertnstert.2014.06.032","article-title":"Physical activity is not related to semen quality in young healthy men","volume":"102","author":"Chavarro","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/1477-7827-10-115","article-title":"The combination matters-Distinct impact of lifestyle factors on sperm quality: A study on semen analysis of 1683 patients according to MSOME criteria","volume":"10","author":"Wogatzky","year":"2012","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1055\/s-2005-872906","article-title":"Reproductive Profile of Physically Active Men After Exhaustive Endurance Exercise","volume":"27","author":"Vaamonde","year":"2006","journal-title":"Int. J. Sports Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1055\/s-2004-819933","article-title":"Sperm Characteristics of Endurance Trained Cyclists","volume":"25","author":"Gebreegziabher","year":"2004","journal-title":"Int. J. Sports Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1093\/humrep\/deu212","article-title":"Paternal physical and sedentary activities in relation to semen quality and reproductive outcomes among couples from a fertility center","volume":"29","author":"Gaskins","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., and Chang, Y. (2010). Sirtuin 3, a New Target of PGC-1\u03b1, Plays an Important Role in the Suppression of ROS and Mitochondrial Biogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011707"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbabio.2013.12.008","article-title":"Pre-diabetes alters testicular PGC1-\u03b1\/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stress","volume":"1837","author":"Rato","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1093\/jpp\/rgac011","article-title":"Hyperoside, a natural flavonoid compound, attenuates Triptolide-induced testicular damage by activating the Keap1-Nrf2 and SIRT1-PGC1\u03b1 signalling pathway","volume":"74","author":"Wang","year":"2022","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/molehr\/gaz063","article-title":"Stress response pathways in the male germ cells and gametes","volume":"26","author":"Santiago","year":"2020","journal-title":"Mol. Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e65703","DOI":"10.7554\/eLife.65703","article-title":"eIF2B conformation and assembly state regulate the integrated stress response","volume":"10","author":"Schoof","year":"2021","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/cdd.2017.152","article-title":"Oxidative stress promotes SIRT1 recruitment to the GADD34\/PP1\u03b1 complex to activate its deacetylase function","volume":"25","author":"Lee","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/jcsm.12178","article-title":"Mitochondria and ageing: Role in heart, skeletal muscle and adipose tissue","volume":"8","author":"Boengler","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8321","DOI":"10.18632\/aging.103141","article-title":"Mitochondria-related miR-574 reduces sperm ATP by targeting ND5 in aging males","volume":"12","author":"Ma","year":"2020","journal-title":"Aging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s10522-014-9526-z","article-title":"Mitochondrial adaptations evoked with exercise are associated with a reduction in age-induced testicular atrophy in Fischer-344 rats","volume":"15","author":"Joseph","year":"2014","journal-title":"Biogerontology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105370","DOI":"10.1016\/j.jsbmb.2019.04.019","article-title":"Transcription regulation of NRF1 on StAR reduces testosterone synthesis in hypoxemic murine","volume":"191","author":"Wang","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s13238-020-00771-1","article-title":"Sirt1 regulates testosterone biosynthesis in Leydig cells via modulating autophagy","volume":"12","author":"Khawar","year":"2021","journal-title":"Protein Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.fertnstert.2012.04.008","article-title":"Sirt1 exerts anti-inflammatory effects and promotes steroidogenesis in Leydig cells","volume":"98","author":"Wu","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1126\/science.1201940","article-title":"Mitochondria and the Autophagy-Inflammation-Cell Death Axis in Organismal Aging","volume":"333","author":"Green","year":"2011","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2011.07.030","article-title":"Autophagy and Aging","volume":"146","author":"Rubinsztein","year":"2011","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.exger.2013.06.010","article-title":"Oxidative stress in testis of animals during aging with and without reproductive activity","volume":"48","author":"Salomon","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jsbmb.2003.10.007","article-title":"Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells","volume":"88","author":"Cao","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_34","first-page":"23","article-title":"Analysis of age-associated changes in mitochondrial free radical generation by rat testis","volume":"307","author":"Capin","year":"2008","journal-title":"Mol. Cell. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Noblanc, A., Klaassen, A., and Robaire, B. (2020). The Exacerbation of Aging and Oxidative Stress in the Epididymis of Sod1 Null Mice. Antioxidants, 9.","DOI":"10.3390\/antiox9020151"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3109\/19396368.2015.1008071","article-title":"Oxidative status in testis and epididymal sperm parameters after acute and chronic stress by cold-water immersion in the adult rat","volume":"61","year":"2015","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3164\/jcbn.12-85","article-title":"Aging decreases antioxidant effects and increases lipid peroxidation in the Apolipoprotein E deficient mouse","volume":"52","author":"Honma","year":"2013","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12033-007-0048-7","article-title":"Alterations in antioxidant enzymes during aging in humans","volume":"37","author":"Rizvi","year":"2007","journal-title":"Mol. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Santiago, J., Silva, J.V., and Fardilha, M. (2019). First Insights on the Presence of the Unfolded Protein Response in Human Spermatozoa. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215518"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s12192-017-0765-1","article-title":"Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell","volume":"22","author":"Arrigo","year":"2017","journal-title":"Cell Stress Chaperones"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.fertnstert.2015.06.039","article-title":"Profiling signaling proteins in human spermatozoa: Biomarker identification for sperm quality evaluation","volume":"104","author":"Silva","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18947","DOI":"10.1074\/jbc.274.27.18947","article-title":"Regulation of Hsp27 Oligomerization, Chaperone Function, and Protective Activity against Oxidative Stress\/Tumor Necrosis Factor \u03b1 by Phosphorylation","volume":"274","author":"Rogalla","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1074\/jbc.M512553200","article-title":"Self-association and Chaperone Activity of Hsp27 Are Thermally Activated","volume":"281","author":"Mauk","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5281","DOI":"10.1074\/jbc.M407236200","article-title":"Mechanism of Chaperone Function in Small Heat Shock Proteins","volume":"280","author":"Shashidharamurthy","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7058350","DOI":"10.1155\/2019\/7058350","article-title":"Stay Fit, Stay Young: Mitochondria in Movement: The Role of Exercise in the New Mitochondrial Paradigm","volume":"2019","author":"Huertas","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.nut.2015.02.005","article-title":"Exercise and oxidative stress: Potential effects of antioxidant dietary strategies in sports","volume":"31","author":"Pingitore","year":"2015","journal-title":"Nutrition"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1152\/physrev.00031.2007","article-title":"Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production","volume":"88","author":"Powers","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1046\/j.1365-201X.2003.01095.x","article-title":"Effect of intensive exercise-induced testicular gametogenic and steroidogenic disorders in mature male Wistar strain rats: A correlative approach to oxidative stress","volume":"178","author":"Manna","year":"2003","journal-title":"Acta Physiol. Scand."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1089\/omi.2015.0065","article-title":"Physical Activity, Exercise, and Mammalian Testis Function: Emerging Preclinical Protein Biomarker and Integrative Biology Insights","volume":"19","author":"Gomes","year":"2015","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e14520","DOI":"10.1111\/and.14520","article-title":"Running exercise training-induced impact on oxidative stress and mitochondria-related apoptosis in rat\u2019s testicles","volume":"54","author":"Nazanin","year":"2022","journal-title":"Andrologia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1530\/JOE-14-0638","article-title":"Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction","volume":"225","author":"Wang","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1089\/neu.2018.6266","article-title":"Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration","volume":"36","author":"Carteri","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"110631","DOI":"10.1016\/j.mce.2019.110631","article-title":"Testosterone induces up-regulation of mitochondrial gene expression in murine C2C12 skeletal muscle cells accompanied by an increase of nuclear respiratory factor-1 and its downstream effectors","volume":"500","author":"Pronsato","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s13353-020-00550-y","article-title":"Testosterone increases apoptotic cell death and decreases mitophagy in Leber\u2019s hereditary optic neuropathy cells","volume":"61","author":"Ambroziak","year":"2020","journal-title":"J. Appl. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.abb.2018.05.002","article-title":"Testosterone alleviates mitochondrial ROS accumulation and mitochondria-mediated apoptosis in the gastric mucosa of orchiectomized rats","volume":"649","author":"Kang","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.3892\/mmr.2017.7120","article-title":"Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/j.1742-4658.2012.08535.x","article-title":"Exploiting the selectivity of protein phosphatase 1 for pharmacological intervention","volume":"280","author":"Tsaytler","year":"2013","journal-title":"FEBS J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1126\/science.1101902","article-title":"A Selective Inhibitor of eIF2a Dephosphorylation Protects Cells from ER Stress","volume":"307","author":"Boyce","year":"2005","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1095\/biolreprod54.3.719","article-title":"Primate sperm contain protein phosphatase 1, a biochemical mediator of motility","volume":"54","author":"Smith","year":"1996","journal-title":"Biol. Reprod."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:01Z","timestamp":1760143501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":61,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911619"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911619","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}