{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:32:42Z","timestamp":1777044762916,"version":"3.51.4"},"reference-count":203,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Tumor cells are highly resistant to oxidative stress resulting from the imbalance between high reactive oxygen species (ROS) production and insufficient antioxidant defenses. However, when intracellular levels of ROS rise beyond a certain threshold, largely above cancer cells\u2019 capacity to reduce it, they may ultimately lead to apoptosis or necrosis. This is, in fact, one of the molecular mechanisms of anticancer drugs, as most chemotherapeutic treatments alter redox homeostasis by further elevation of intracellular ROS levels or inhibition of antioxidant pathways. In traditional chemotherapy, it is widely accepted that most therapeutic effects are due to ROS-mediated cell damage, but in targeted therapies, ROS-mediated effects are mostly unknown and data are still emerging. The increasing effectiveness of anticancer treatments has raised new challenges, especially in the field of reproduction. With cancer patients\u2019 life expectancy increasing, many aiming to become parents will be confronted with the adverse effects of treatments. Consequently, concerns about the impact of anticancer therapies on reproductive capacity are of particular interest. In this review, we begin with a short introduction on anticancer therapies, then address ROS physiological\/pathophysiological roles in both male and female reproductive systems, and finish with ROS-mediated adverse effects of anticancer treatments in reproduction.<\/jats:p>","DOI":"10.3390\/cancers14061585","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"1585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0002-0303","authenticated-orcid":false,"given":"Sara","family":"Mendes","sequence":"first","affiliation":[{"name":"Department of Physical Education and Sports, University Institute of Maia (ISMAI), 4475-690 Maia, Portugal"},{"name":"Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-3822","authenticated-orcid":false,"given":"Ros\u00e1lia","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4099-002 Porto, Portugal"}]},{"given":"Manuel","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4099-002 Porto, Portugal"},{"name":"Department of Oncology, University Hospital Center of Porto (CHUP), Largo do Prof. Abel Salazar, 4099-001 Porto, Portugal"}]},{"given":"Franklim","family":"Marques","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center of Porto (CHUP), Largo do Prof. Abel Salazar, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-3290","authenticated-orcid":false,"given":"M\u00e1rio","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4099-002 Porto, Portugal"}]},{"given":"Elisabete","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of General Physiology, Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology (IBMC), Institute for Research & Innovation in Health (I3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nrc1529","article-title":"Timeline: Chemotherapy and the War on Cancer","volume":"5","author":"Chabner","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5381692","DOI":"10.1155\/2019\/5381692","article-title":"Understanding of ROS-Inducing Strategy in Anticancer Therapy","volume":"2019","author":"Kim","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.placenta.2015.06.016","article-title":"Oxidative stress-induced C\/EBPbeta inhibits beta-catenin signaling molecule involving in the pathology of Preeclampsia","volume":"36","author":"Zhuang","year":"2015","journal-title":"Placenta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"145774","DOI":"10.1016\/j.gene.2021.145774","article-title":"Suppressing effects of green tea extract and Epigallocatechin-3-gallate (EGCG) on TGF-\u03b2- induced Epitheli-al-to-mesenchymal transition via ROS\/Smad signaling in human cervical cancer cells","volume":"794","author":"Panji","year":"2021","journal-title":"Gene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.2147\/IJN.S277014","article-title":"ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nano-particles","volume":"16","author":"Piktel","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1111\/jog.14779","article-title":"Erastin synergizes with cisplatin via ferroptosis to inhibit ovarian cancer growth in vitro and in vivo","volume":"47","author":"Cheng","year":"2021","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"795602","DOI":"10.1155\/2015\/795602","article-title":"Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress","volume":"2015","author":"Angsutararux","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.toxlet.2015.06.012","article-title":"An integrated view of cisplatin-induced nephrotoxicity and ototoxicity","volume":"237","author":"Karasawa","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/eye.2017.222","article-title":"Neuro-ophthalmic side effects of molecularly targeted cancer drugs","volume":"32","author":"Bhatti","year":"2017","journal-title":"Eye"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrd3003","article-title":"The safety and side effects of monoclonal antibodies","volume":"9","author":"Hansel","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13054-017-1678-1","article-title":"New drugs, new toxicities: Severe side effects of modern targeted and immunotherapy of cancer and their management","volume":"21","author":"Kroschinsky","year":"2017","journal-title":"Crit. Care"},{"key":"ref_13","first-page":"227","article-title":"Antibodies in diagnosis and therapy. The magic bullet--nearing the century mark","volume":"1","author":"Raso","year":"1990","journal-title":"Semin. Cancer Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-59745-554-1_1","article-title":"Therapeutic antibodies: Current state and future trends\u2014Is a paradigm change coming soon?","volume":"525","author":"Dimitrov","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1485283","DOI":"10.1155\/2017\/1485283","article-title":"Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy","volume":"2017","author":"Teppo","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.fertnstert.2013.08.010","article-title":"Effects of chemotherapy and radiotherapy on spermatogenesis in humans","volume":"100","author":"Meistrich","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.urology.2008.08.474","article-title":"Male Fertility after Cancer","volume":"73","author":"Sabanegh","year":"2009","journal-title":"Urology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/humupd\/7.6.535","article-title":"The effects of radiotherapy and chemotherapy on female reproduction","volume":"7","author":"Meirow","year":"2001","journal-title":"Hum. Reprod. Update"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/GRF.0b013e3181f96b54","article-title":"Toxicity of Chemotherapy and Radiation on Female Reproduction","volume":"53","author":"Meirow","year":"2010","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1462-3889(02)00081-9","article-title":"The effect of cytotoxic chemotherapy on female fertility","volume":"7","author":"Chasle","year":"2003","journal-title":"Eur. J. Oncol. Nurs."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S0094-0143(02)00079-4","article-title":"Common medications and drugs: How they affect male fertility","volume":"29","author":"Nudell","year":"2002","journal-title":"Urol. Clin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1200\/JCO.2008.20.1541","article-title":"Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study","volume":"27","author":"Green","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/OGX.0b013e318224e97b","article-title":"The Effects of Chemotherapy and Radiotherapy on Fertility in Premenopausal Women","volume":"66","author":"Fleischer","year":"2011","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.eururo.2007.03.085","article-title":"Semen Quality in Men with Malignant Diseases before and after Therapy and the Role of Cryopreservation","volume":"52","author":"Trottmann","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.fertnstert.2013.07.1974","article-title":"The determination of reproductive safety in men during and after cancer treatment","volume":"100","author":"Choy","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"382","DOI":"10.5468\/ogs.2019.62.6.382","article-title":"Consequences of chemotherapeutic agents on primordial follicles and future clinical applica-tions","volume":"62","author":"Kim","year":"2019","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Stefansdottir, A., Johnston, Z.C., Powles-Glover, N., Anderson, R.A., Adams, I.R., and Spears, N. (2016). Etoposide damages female germ cells in the developing ovary. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2505-9"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/hon.939","article-title":"Fertility preservation after chemotherapy for Hodgkin lymphoma","volume":"28","author":"Simmons","year":"2010","journal-title":"Hematol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.fertnstert.2013.09.011","article-title":"Introduction: Cancer treatment and male fertility: Effects of therapy and current and future management options","volume":"100","author":"Sigman","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.fertnstert.2009.10.008","article-title":"A nationwide survey of oncologists regarding treatment-related infertility and fertility preservation in female cancer patients","volume":"94","author":"Forman","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/pbc.22004","article-title":"Male gonadal toxicity","volume":"53","author":"Meistrich","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1470-2045(05)70092-9","article-title":"Fertility preservation for young patients with cancer: Who is at risk and what can be offered?","volume":"6","author":"Wallace","year":"2005","journal-title":"Lancet Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3816\/CLM.2004.n.013","article-title":"The Impact of Conventional and High-Dose Therapy for Lymphoma on Fertility","volume":"5","author":"Grigg","year":"2004","journal-title":"Clin. Lymphoma"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0890-6238(01)00182-4","article-title":"The impact of chemotherapy on male fertility: A survey of the biologic basis and clinical aspects","volume":"15","author":"Schrader","year":"2001","journal-title":"Reprod. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lambertini, M., Del Mastro, L., Pescio, M.C., Andersen, C.Y., Azim, H.A., Peccatori, F.A., Costa, M., Revelli, A., Salvagno, F., and Gennari, A. (2016). Cancer and fertility preservation: International recommendations from an expert meeting. BMC Med., 14.","DOI":"10.1186\/s12916-015-0545-7"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rabaca, A., Sousa, M., Alves, M.G., Oliveira, P.F., and S\u00e1, R. (2015). Novel drug therapies for fertility preservation in men undergoing chemotherapy: Clinical relevance of pro-tector agents. Curr. Med. Chem., 3347\u20133369.","DOI":"10.2174\/0929867322666150821094334"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bpobgyn.2011.11.008","article-title":"Chemotherapy and fertility","volume":"26","author":"Blumenfeld","year":"2012","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.2174\/1871520611009010092","article-title":"Male fertility-implications of anticancer treatment and strategies to mitigate gonadotoxicity","volume":"10","author":"Ahmed","year":"2010","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ctrv.2003.07.005","article-title":"Male fertility preservation and cancer treatment","volume":"30","author":"Puscheck","year":"2004","journal-title":"Cancer Treat. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.soncn.2009.08.001","article-title":"Fertility Concerns for Young Males Undergoing Cancer Therapy","volume":"25","author":"Hobbie","year":"2009","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1080\/01926230290166724","article-title":"Invited Review: Oxidation of Biological Systems: Oxidative Stress Phenomena, Antioxidants, Redox Reactions, and Methods for Their Quantification","volume":"30","author":"Kohen","year":"2002","journal-title":"Toxicol. Pathol."},{"key":"ref_42","first-page":"5","article-title":"Oxygen-derived species: Their relation to human disease and environmental stress. Environ","volume":"102","author":"Halliwell","year":"1994","journal-title":"Health Perspect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0300-483X(00)00231-6","article-title":"The Haber-Weiss reaction and mechanisms of toxicity","volume":"149","author":"Kehrer","year":"2000","journal-title":"Toxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jprot.2013.05.006","article-title":"Actin carbonylation: From cell dysfunction to organism disorder","volume":"92","author":"Castro","year":"2013","journal-title":"J. Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/ndt\/gfm077","article-title":"Novel sources of reactive oxygen species in the human body","volume":"22","author":"Orient","year":"2007","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1159\/000485089","article-title":"Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species","volume":"44","author":"He","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.advms.2017.05.005","article-title":"Endogenous non-enzymatic antioxidants in the human body","volume":"63","author":"Witkowska","year":"2018","journal-title":"Adv. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcp.10119","article-title":"Cellular response to oxidative stress: Signaling for suicide and survival","volume":"192","author":"Martindale","year":"2002","journal-title":"J. Cell. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4350965","DOI":"10.1155\/2016\/4350965","article-title":"ROS and ROS-mediated cellular signaling","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1242\/jcs.00963","article-title":"The JAK\/STAT signaling pathway","volume":"117","author":"Rawlings","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","article-title":"The Phosphoinositide 3-Kinase Pathway","volume":"296","author":"Cantley","year":"2002","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative Stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.redox.2015.01.002","article-title":"Oxidative stress: A concept in redox biology and medicine","volume":"4","author":"Sies","year":"2015","journal-title":"Redox Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/aja.1001120103","article-title":"The cycle of the seminiferous epithelium in man","volume":"112","author":"Clermont","year":"1963","journal-title":"Am. J. Anat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/978-0-387-09597-4_5","article-title":"Extracellular Matrix and Its Role in Spermatogenesis","volume":"636","author":"Siu","year":"2009","journal-title":"Mol. Mech. Spermatogenesis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1098\/rstb.2010.0026","article-title":"Spermatogonial stem cell regulation and spermatogenesis","volume":"365","author":"Phillips","year":"2010","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_58","first-page":"1","article-title":"Spermatogenesis and cycle of the seminiferous epithelium","volume":"636","author":"Hess","year":"2008","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00013.2015","article-title":"Spermatogenesis: The Commitment to Meiosis","volume":"96","author":"Griswold","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.gene.2019.05.027","article-title":"The dynamics and regulation of chromatin remodeling during spermiogenesis","volume":"706","author":"Hao","year":"2019","journal-title":"Gene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/jemt.10315","article-title":"Organization and modifications of sperm acrosomal molecules during spermatogenesis and epi-didymal maturation","volume":"61","author":"Yoshinaga","year":"2003","journal-title":"Microsc. Res. Tech."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1006\/scdb.1998.0203","article-title":"The central role of Sertoli cells in spermatogenesis","volume":"9","author":"Griswold","year":"1998","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/jcp.1041510305","article-title":"Reactive oxygen species and human spermatozoa: Analysis of the cellular mecha-nisms involved in luminol- and lucigenin-dependent chemiluminescence","volume":"151","author":"Aitken","year":"1992","journal-title":"J. Cell. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3109\/01485019208987691","article-title":"Nadh-Dependent Oxidoreductase (Diaphorase) Activity and Isozyme Pattern of Sperm in Infertile Men","volume":"28","author":"Gavella","year":"1992","journal-title":"Arch. Androl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/humrep\/16.9.1912","article-title":"Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation","volume":"16","author":"Ollero","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/(SICI)1097-010X(19970401)277:5<390::AID-JEZ5>3.0.CO;2-K","article-title":"Comparative analysis of the ability of precursor germ cells and epididymal spermatozoa to generate reactive oxygen metabolites","volume":"277","author":"Fisher","year":"1997","journal-title":"J. Exp. Zool."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1095\/biolreprod65.1.119","article-title":"Expression of stress response genes in germ cells during spermatogenesis","volume":"65","author":"Hales","year":"2001","journal-title":"Biol. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/jrf.0.1150001","article-title":"The amoroso lecture. The human spermatozoon--a cell in crisis?","volume":"115","author":"Aitken","year":"1999","journal-title":"J. Reprod. Fertil."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1093\/humrep\/13.8.2172","article-title":"Selenium in human male reproductive organs","volume":"13","author":"Oldereid","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S0015-0282(00)01591-0","article-title":"Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa","volume":"74","author":"Kemal","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1071\/RD9950659","article-title":"Free radicals, lipid peroxidation and sperm function","volume":"7","author":"Aitken","year":"1995","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1472-6483(10)61730-0","article-title":"Oxidative stress in the male germ line and its role in the aetiology of male infertility and genetic disease","volume":"7","author":"Aitken","year":"2003","journal-title":"Reprod. Biomed. Online"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/S1472-6483(10)61641-0","article-title":"Role of antioxidants in treatment of male infertility: An overview of the literature","volume":"8","author":"Agarwal","year":"2004","journal-title":"Reprod. Biomed. Online"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1590\/S1677-55382007000500002","article-title":"Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: An evidence based analysis","volume":"33","author":"Cocuzza","year":"2007","journal-title":"Int. Braz. J. Urol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1210\/me.2010-0489","article-title":"Reactive oxygen species (ROS) play a critical role in the cAMP-induced activation of Ras and the phos-phorylation of ERK1\/2 in Leydig cells","volume":"25","author":"Tai","year":"2011","journal-title":"Mol. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0015-0282(16)56895-2","article-title":"Reactive oxygen species released by activated neutrophils, but not by deficient spermatozoa, are sufficient to affect normal sperm motility","volume":"62","author":"Plante","year":"1994","journal-title":"Fertil. Steril."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0015-0282(02)04948-8","article-title":"Role of reactive oxygen species in the pathophysiology of human reproduction","volume":"79","author":"Agarwal","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_78","first-page":"61","article-title":"Antioxidants and infertility treatment, the role of Satureja Khuzestanica: A mini-systematic review","volume":"9","author":"Safarnavadeh","year":"2011","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s13273-017-0015-8","article-title":"Actions and mechanisms of reactive oxygen species and antioxidative system in semen","volume":"13","author":"Gao","year":"2017","journal-title":"Mol. Cell. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00018-019-03253-8","article-title":"Oxidative stress and male infertility: Current knowledge of pathophysiology and role of antioxidant therapy in disease management","volume":"77","author":"Barati","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"193","DOI":"10.5152\/eurasianjmed.2018.17397","article-title":"Reactive Oxygen Species: The Dual Role in Physiological and Pathological Conditions of the Human Body","volume":"50","author":"Bardaweel","year":"2018","journal-title":"Eurasian J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Berby, B., Bichara, C., Rives-Feraille, A., Jumeau, F., Pizio, P., S\u00e9tif, V., Sibert, L., Dumont, L., Rondanino, C., and Rives, N. (2021). Oxidative Stress Is Associated with Telomere Interaction Impairment and Chromatin Condensation Defects in Spermatozoa of Infertile Males. Antioxidants, 10.","DOI":"10.3390\/antiox10040593"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.rbmo.2018.06.023","article-title":"Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management-meta-analyses","volume":"37","author":"Santi","year":"2018","journal-title":"Reprod. Biomed. Online"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5534\/wjmh.190055","article-title":"Male oxidative stress infertility (MOSI): Proposed terminology and clinical practice guidelines for man-agement of idiopathic male infertility","volume":"37","author":"Agarwal","year":"2019","journal-title":"World J. Mens Health"},{"key":"ref_85","unstructured":"Chian, R.-C., Nargund, G., and Huang, J.Y.J. (2017). Follicular Development and Oocyte Growth. Development of In Vitro Maturation for Human Oocytes: Natural and Mild Approaches to Clinical Infertility Treatment, Springer International Publishing."},{"key":"ref_86","first-page":"a005553","article-title":"Developmental Control of Oocyte Maturation and Egg Activation in Metazoan Models","volume":"3","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_87","first-page":"417","article-title":"A quantitative and cytological study of germ cells in human ovaries","volume":"158","author":"Baker","year":"1963","journal-title":"Proc. R. Soc. Lond. Ser. B Boil. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1530\/jrf.0.0810433","article-title":"Morphometric studies of small follicles in ovaries of women at different ages","volume":"81","author":"Gougeon","year":"1987","journal-title":"Reproduction"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/j.bbadis.2012.05.013","article-title":"Molecular control of oogenesis","volume":"1822","author":"Smitz","year":"2012","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_90","first-page":"167","article-title":"Ovarian Folliculogenesis. Results Probl","volume":"58","author":"Alyagor","year":"2016","journal-title":"Cell Differ."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/humupd\/dmr039","article-title":"Ovarian antral folliculogenesis during the human menstrual cycle: A review","volume":"18","author":"Baerwald","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2014-1045","article-title":"Cyclic Decidualization of the Human Endometrium in Reproductive Health and Failure","volume":"35","author":"Gellersen","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/humupd\/dml020","article-title":"Ovarian feedback, mechanism of action and possible clinical implications","volume":"12","author":"Messinis","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/OGX.0b013e3181932a37","article-title":"Physiological changes associated with the menstrual cycle: A review","volume":"64","author":"Farage","year":"2009","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1600-0757.2011.00409.x","article-title":"Physiology of the female reproductive axis","volume":"61","author":"Bates","year":"2012","journal-title":"Periodontology 2000"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/096032718800700102","article-title":"Free Radicals and Antioxidant Protection: Mechanisms and Significance in Toxicology and Disease","volume":"7","author":"Halliwell","year":"1988","journal-title":"Hum. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1530\/jrf.0.0970347","article-title":"Changes in activities of superoxide dismutase and lipid peroxide in corpus luteum during pregnancy in rats","volume":"97","author":"Sugino","year":"1993","journal-title":"Reproduction"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1095\/biolreprod.111.095224","article-title":"Roles of Reactive Oxygen Species and Antioxidants in Ovarian Toxicity","volume":"86","author":"Devine","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1073\/pnas.1017213108","article-title":"Reactive oxygen species are indispensable in ovulation","volume":"108","author":"Shkolnik","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/GCO.0b013e32832924ba","article-title":"Impact of oxidative stress on female fertility","volume":"21","author":"Ruder","year":"2009","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S0015-0282(99)00332-5","article-title":"Superoxide dismutase in normal cycling human ovaries: Immunohistochemical localization and characterization","volume":"72","author":"Suzuki","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Shi, L., Zhang, J., Lai, Z., Tian, Y., Fang, L., Wu, M., Xiong, J., Qin, X., Luo, A., and Wang, S. (2016). Long-Term Moderate Oxidative Stress Decreased Ovarian Reproductive Function by Reducing Follicle Quality and Progesterone Production. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162194"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1095\/biolreprod.114.127746","article-title":"Antioxidant Supplementation Modulates Age-Related Placental Bed Morphology and Reproductive Outcome in Mice","volume":"93","author":"Silva","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_104","first-page":"5316984","article-title":"Apocynin Dietary Supplementation Delays Mouse Ovarian Ageing","volume":"2019","author":"Ferreira","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1477-7827-11-74","article-title":"Analysis of oxidative stress during the menstrual cycle","volume":"11","author":"Cornelli","year":"2013","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1161\/01.RES.0000082334.17947.11","article-title":"Modulation of Antioxidant Enzyme Expression and Function by Estrogen","volume":"93","author":"Strehlow","year":"2003","journal-title":"Circ. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.febslet.2014.02.043","article-title":"Differential expression and anti-oxidant function of glutathione peroxidase 3 in mouse uterus during decidualization","volume":"588","author":"Xu","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/molehr\/6.1.19","article-title":"Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy","volume":"6","author":"Sugino","year":"2000","journal-title":"Mol. Hum. Reprod."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.rbmo.2012.08.004","article-title":"Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress","volume":"25","author":"Garrel","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.siny.2010.04.001","article-title":"Maturation of the antioxidant system and the effects on preterm birth","volume":"15","author":"Davis","year":"2010","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_112","first-page":"6","article-title":"Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis","volume":"118","year":"2010","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.freeradbiomed.2020.03.020","article-title":"Age-related oxidative modifications to uterine albumin impair extravillous trophoblast cells function","volume":"152","author":"Mendes","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"9174521","DOI":"10.1155\/2019\/9174521","article-title":"New Insights into the Process of Placentation and the Role of Oxidative Uterine Microenvironment","volume":"2019","author":"Mendes","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1054\/mehy.1999.0982","article-title":"A threshold concept for cancer therapy","volume":"55","author":"Kong","year":"2000","journal-title":"Med. Hypotheses"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev.pharmtox.44.101802.121851","article-title":"The Role of Oxidative Stress in Carcinogenesis","volume":"44","author":"Klaunig","year":"2004","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1080\/21541248.2016.1192714","article-title":"KRas, ROS and the initiation of pancreatic cancer","volume":"8","author":"Storz","year":"2016","journal-title":"Small GTPases"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrd2803","article-title":"Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic ap-proach?","volume":"8","author":"Trachootham","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00432-017-2464-9","article-title":"ROS-modulated therapeutic approaches in cancer treatment","volume":"143","author":"Raza","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.4161\/cbt.7.12.7067","article-title":"Cancer cell killing via ROS: To increase or decrease, that is the question","volume":"7","author":"Wang","year":"2008","journal-title":"Cancer Biol. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/nm1001-1111","article-title":"Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells","volume":"7","author":"Hwang","year":"2001","journal-title":"Nat. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"745","DOI":"10.4161\/cbt.5.7.2971","article-title":"Proteasome inhibitor induces apoptosis through induction of endoplasmic reticulum stress","volume":"5","author":"Fribley","year":"2006","journal-title":"Cancer Biol. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Marullo, R., Werner, E., Degtyareva, N., Moore, B., Altavilla, G., Ramalingam, S.S., and Doetsch, P.W. (2013). Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081162"},{"key":"ref_124","first-page":"440","article-title":"Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharmacogenet","volume":"21","author":"Thorn","year":"2011","journal-title":"Genomics"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1002\/cam4.881","article-title":"Erlotinib induces the human non-small-cell lung cancer cells apoptosis via activating ROS-dependent JNK pathways","volume":"5","author":"Shan","year":"2016","journal-title":"Cancer Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jdermsci.2011.03.001","article-title":"Imatinib mesylate induction of ROS-dependent apoptosis in melanoma B16F0 cells","volume":"62","author":"Chang","year":"2011","journal-title":"J. Dermatol. Sci."},{"key":"ref_127","first-page":"836","article-title":"Rituximab modifies the cisplatin-mitochondrial signaling pathway, resulting in apoptosis in cisplatin-resistant non-Hodgkin\u2019s lymphoma","volume":"8","author":"Alas","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1016\/S0021-9258(18)35980-5","article-title":"Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homo-cysteine sulfoximine)","volume":"254","author":"Griffith","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1158\/1541-7786.MCR-11-0359","article-title":"Imexon Induces an Oxidative Endoplasmic Reticulum Stress Response in Pancreatic Cancer Cells","volume":"10","author":"Sheveleva","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_130","first-page":"787","article-title":"Increased level of the p67phox subunit of NADPH oxidase by 4HPR in head and neck squamous carcinoma cells","volume":"27","author":"Kim","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.freeradbiomed.2007.03.035","article-title":"NQO1-activated phenothiazinium redox cyclers for the targeted bioreductive induction of cancer cell apop-tosis","volume":"43","author":"Wondrak","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"37832","DOI":"10.1074\/jbc.M301546200","article-title":"Inhibition of mitochondrial respiration: A novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism","volume":"278","author":"Pelicano","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"17179","DOI":"10.1074\/jbc.M111604200","article-title":"Transferrin receptor-dependent iron uptake is responsible for doxorubicin-mediated apoptosis in endo-thelial cells: Role of oxidant-induced iron signaling in apoptosis","volume":"277","author":"Kotamraju","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/sj.bjc.6602639","article-title":"The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines","volume":"93","author":"Paine","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0006-2952(00)00380-4","article-title":"Induction of oxidative stress and apoptosis in myeloma cells by the aziridine-containing agent imexon","volume":"60","author":"Dvorakova","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.bcp.2014.07.017","article-title":"Targeting antioxidants for cancer therapy","volume":"92","author":"Glasauer","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ijc.11644","article-title":"Enhancement of chemotherapeutic response of tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin","volume":"109","author":"Fang","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.freeradbiomed.2006.11.032","article-title":"Inhibiting catalase activity sensitizes 36B10 rat glioma cells to oxidative stress","volume":"42","author":"Smith","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1743-7075-10-7","article-title":"Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2\/HO-1 pathway","volume":"10","author":"Kilic","year":"2013","journal-title":"Nutr. Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1055\/s-0028-1088302","article-title":"Nrf2 as a Master Redox Switch in Turning on the Cellular Signaling Involved in the Induction of Cytoprotective Genes by Some Chemopreventive Phytochemicals","volume":"74","author":"Surh","year":"2008","journal-title":"Planta Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3390\/nu6020466","article-title":"Potential Role of Carotenoids as Antioxidants in Human Health and Disease","volume":"6","author":"Fiedor","year":"2014","journal-title":"Nutrients"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4103\/0973-7847.134247","article-title":"Cytotoxicity of dietary flavonoids on different human cancer types","volume":"8","author":"Sak","year":"2014","journal-title":"Pharmacogn. Rev."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"109004","DOI":"10.1016\/j.biopha.2019.109004","article-title":"Flavonoids showed anticancer effects on the ovarian cancer cells: Involvement of reactive oxygen species, apoptosis, cell cycle and invasion","volume":"116","author":"Tavsan","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1080\/10715760500143478","article-title":"Free radical mediated oxidative stress and toxic side effects in brain induced by the anti-cancer drug adriamycin: Insight into chemobrain","volume":"39","author":"Joshi","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10565-006-0140-y","article-title":"Adriamycin-induced oxidative mitochondrial cardiotoxicity","volume":"23","author":"Berthiaume","year":"2006","journal-title":"Cell Biol. Toxicol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.redox.2017.12.013","article-title":"MicroRNA-140-5p aggravates doxorubicin-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2","volume":"15","author":"Zhao","year":"2017","journal-title":"Redox Biol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1089\/ars.2011.3965","article-title":"Chemotherapy-Induced Weakness and Fatigue in Skeletal Muscle: The Role of Oxidative Stress","volume":"15","author":"Gilliam","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/cam4.2072","article-title":"Can acetylcysteine ameliorate cisplatin-induced toxicities and oxidative stress without decreasing antitumor efficacy? A randomized, double-blind, placebo-controlled trial involving patients with head and neck cancer","volume":"8","author":"Visacri","year":"2019","journal-title":"Cancer Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"112269","DOI":"10.1016\/j.jep.2019.112269","article-title":"Protective effect of Liuwei Dihuang Pill on cisplatin-induced reproductive toxicity and genotoxicity in male mice","volume":"247","author":"Zhang","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4149\/gpb_2019006","article-title":"Effect of lycopene on oxidative ovary-damage induced by cisplatin in rats","volume":"38","author":"Kulhan","year":"2019","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_151","first-page":"3575","article-title":"Cytotoxic effects of chemotherapeutic drugs on mouse testis cells","volume":"39","author":"Lu","year":"1979","journal-title":"Cancer Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1200\/JCO.1999.17.5.1493","article-title":"Testicular Function After Cytotoxic Chemotherapy: Evidence of Leydig Cell Insufficiency","volume":"17","author":"Howell","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/1097-0142(20010401)91:7<1297::AID-CNCR1132>3.0.CO;2-Z","article-title":"The impact of chemotherapy on Leydig cell function in long term survivors of germ cell tumors","volume":"91","author":"Gerl","year":"2001","journal-title":"Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.2217\/fon-2016-0176","article-title":"Chemotherapy-induced damage to ovary: Mechanisms and clinical impact","volume":"12","author":"Bedoschi","year":"2016","journal-title":"Future Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2165\/00002018-200528050-00004","article-title":"Chemotherapy-induced ovarian failure: Manifestations and management","volume":"28","author":"Molina","year":"2005","journal-title":"Drug Saf."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"25310","DOI":"10.18632\/oncotarget.15813","article-title":"Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/humupd\/7.4.394","article-title":"Genetic and teratogenic effects of cancer treatments on gametes and embryos","volume":"7","author":"Arnon","year":"2001","journal-title":"Hum. Reprod. Update"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Hales, B.F., Barton, T.S., and Robaire, B. (2005). Impact of Paternal Exposure to Chemotherapy on Offspring in the Rat. J. Natl. Cancer Inst. Monogr., 28\u201331.","DOI":"10.1093\/jncimonographs\/lgi028"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1200\/JCO.2011.37.2938","article-title":"Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study","volume":"30","author":"Signorello","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41467-019-08290-2","article-title":"Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs","volume":"10","author":"Yimit","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.1158\/1078-0432.CCR-06-1037","article-title":"Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mito-chondrial membrane of head and neck squamous cell carcinoma: Possible role in apoptosis","volume":"12","author":"Yang","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1016\/j.fertnstert.2007.04.059","article-title":"Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid","volume":"89","author":"Ceribasi","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1080\/13880209.2017.1322618","article-title":"Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes","volume":"55","author":"Fouad","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Wang, T.-E., Lai, Y.-H., Yang, K.-C., Lin, S.-J., Chen, C.-L., and Tsai, P.-S. (2020). Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol. Antioxidants, 9.","DOI":"10.3390\/antiox9080723"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cbi.2012.08.012","article-title":"Cisplatin inhibits testosterone synthesis by a mechanism that includes the action of reactive oxygen species (ROS) at the level of P450scc","volume":"199","author":"Acquier","year":"2012","journal-title":"Chem. Interact."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Afsar, T., Razak, S., Khan, M.R., and Almajwal, A. (2017). Acacia hydaspica ethyl acetate extract protects against cisplatin-induced DNA damage, oxidative stress and testicular injuries in adult male rats. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3898-9"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e12593","DOI":"10.1111\/and.12593","article-title":"Rutin ameliorates cisplatin-induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats","volume":"49","author":"Aksu","year":"2016","journal-title":"Andrologia"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12958-018-0426-y","article-title":"Protective effects of mangafodipir against chemotherapy-induced ovarian damage in mice","volume":"16","author":"Qin","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s43032-020-00305-4","article-title":"Involvement of PTEN and FOXO3a Proteins in the Protective Activity of Protocatechuic Acid Against Cisplatin-Induced Ovarian Toxicity in Mice","volume":"28","author":"Gouveia","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3802\/jgo.2013.24.2.177","article-title":"The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats","volume":"24","author":"Li","year":"2013","journal-title":"J. Gynecol. Oncol."},{"key":"ref_171","first-page":"410","article-title":"Protective effect of resveratrol against oxidative damage to ovarian reserve in female Sprague-Dawley rats. Reprod","volume":"31","author":"Akkaya","year":"2015","journal-title":"Biomed. Online"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"627240","DOI":"10.1155\/2013\/327240","article-title":"The Effect of Mirtazapine on Cisplatin-Induced Oxidative Damage and Infertility in Rat Ovaries","volume":"2013","author":"Altuner","year":"2013","journal-title":"Sci. World J."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1039\/c9tx00052f","article-title":"Protective effects of zinc oxide nanoparticles against doxorubicin induced testicular toxicity and DNA damage in male rats","volume":"8","year":"2019","journal-title":"Toxicol. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e22384","DOI":"10.1002\/jbt.22384","article-title":"Palliative effect of curcumin on doxorubicin-induced testicular damage in male rats","volume":"33","author":"Aksu","year":"2019","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.biopha.2017.10.144","article-title":"Zinc\/alogliptin combination attenuates testicular toxicity induced by doxorubicin in rats: Role of oxidative stress, apoptosis and TGF-\u03b21\/NF-\u03baB signaling","volume":"97","author":"Kabel","year":"2018","journal-title":"Biomed. Pharm."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/andr.12426","article-title":"Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxo-rubicin-treated rats","volume":"6","author":"Cabral","year":"2018","journal-title":"Andrology"},{"key":"ref_177","first-page":"355","article-title":"Effect of nano-zinc oxide on doxorubicin- induced oxidative stress and sperm disorders in adult male Wistar rats","volume":"11","author":"Badkoobeh","year":"2013","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_178","first-page":"5275","article-title":"Assessment of doxorubicin-induced mouse testicular damage by the novel second-harmonic generation microscopy","volume":"9","author":"Yang","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_179","first-page":"e13990","article-title":"Alpha-lipoic acid may ameliorate testicular damage by targeting dox-induced altered antioxidant parameters, mitofusin-2 and apoptotic gene expression","volume":"53","author":"Erdem","year":"2021","journal-title":"Andrology"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/bdr2.1535","article-title":"The impact of mesenchymal stem cells on doxorubicin-induced testicular toxicity and progeny outcome of male prepubertal rats","volume":"111","author":"Abdelaziz","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"108963","DOI":"10.1016\/j.biopha.2019.108963","article-title":"Protective properties of glycogen synthase kinase-3 inhibition against doxorubicin-induced oxi-dative damage to mouse ovarian reserve","volume":"116","author":"Niringiyumukiza","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"7717","DOI":"10.18632\/aging.103061","article-title":"Resveratrol attenuates doxorubicin-induced meiotic failure through inhibiting oxidative stress and apoptosis in mouse oocytes","volume":"12","author":"Han","year":"2020","journal-title":"Aging"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Gonzalez, D.F., and Young, F. (2020). Gamma Tocopherol Reduced Chemotherapeutic-Induced ROS in an Ovarian Granulosa Cell Line, But Not in Breast Cancer Cell Lines In Vitro. Antioxidants, 9.","DOI":"10.3390\/antiox9010051"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"BSR20181424","DOI":"10.1042\/BSR20181424","article-title":"Epigallocatechin-3-gallate inhibits doxorubicin-induced inflammation on human ovarian tissue","volume":"39","author":"Fabbri","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00441-016-2445-3","article-title":"Reactive oxygen species and fibrosis: Further evidence of a significant liaison","volume":"365","author":"Richter","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11934-017-0704-9","article-title":"The effect of targeted therapy for genitourinary malignancies on sexual function and fer-tility","volume":"18","author":"Holland","year":"2017","journal-title":"Curr. Urol. Rep."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.critrevonc.2016.08.005","article-title":"Infertility risk and teratogenicity of molecularly targeted anticancer therapy: A chal-lenging issue","volume":"107","author":"Lorenzi","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1158\/1535-7163.MCT-08-0391","article-title":"Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mi-togen-activated protein kinase pathway","volume":"7","author":"Lioni","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/1476-4598-13-155","article-title":"Bortezomib treatment causes long-term testicular dysfunction in young male mice","volume":"13","author":"Hou","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.taap.2015.04.001","article-title":"The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis","volume":"285","author":"Li","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_191","first-page":"43","article-title":"Toxic effects of 5-Fluorouracil on sperm count in wistar rats","volume":"10","year":"2003","journal-title":"Malays. J. Med. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Focaccetti, C., Bruno, A., Magnani, E., Bartolini, D., Principi, E., Dallaglio, K., Bucci, E.O., Finzi, G., Sessa, F., and Noonan, D.M. (2015). Effects of 5-Fluorouracil on Morphology, Cell Cycle, Proliferation, Apoptosis, Autophagy and ROS Production in Endothelial Cells and Cardiomyocytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0115686"},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Fideles, L.S., Miranda, J.A.L., Martins, C.S., Barbosa, M.L.L., Pimenta, H.B., Pimentel, P.V.S., Teixeira, C.S., Scafuri, M.A.S., de Osterno Fa\u00e7anha, S., and Barreto, J.E.F. (2020). Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Re-duction of Inflammation and Oxidative Stress. Molecules, 25.","DOI":"10.3390\/molecules25122786"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bcp.2017.08.024","article-title":"5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition","volume":"145","author":"Bomfin","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1158\/0008-5472.CAN-10-3425","article-title":"Erlotinib-Mediated Inhibition of EGFR Signaling Induces Metabolic Oxidative Stress through NOX4","volume":"71","author":"Orcutt","year":"2011","journal-title":"Cancer Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s11523-017-0521-6","article-title":"Impact of Imatinib on the Fertility of Male Patients with Chronic Myelogenous Leukaemia in the Chronic Phase","volume":"12","author":"Chang","year":"2017","journal-title":"Target. Oncol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.3389\/fphar.2020.01106","article-title":"Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells","volume":"11","author":"Bouitbir","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1038\/s41598-019-39134-0","article-title":"Imatinib treatments have long-term impact on placentation and embryo survival","volume":"9","author":"Salem","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"e453","DOI":"10.1212\/NXI.0000000000000453","article-title":"Rituximab before and during pregnancy: A systematic review, and a case series in MS and NMOSD","volume":"5","author":"Das","year":"2018","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1136\/annrheumdis-2013-203833","article-title":"Fetal outcomes after rituximab exposure in women with autoimmune vasculitis","volume":"72","author":"Pendergraft","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4103\/JNSM.JNSM_38_19","article-title":"Safety of rituximab on testicles, a double-blindedcontrolled trial in mice","volume":"3","year":"2020","journal-title":"J. Nat. Sci. Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"5059043","DOI":"10.1155\/2016\/5059043","article-title":"Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells","volume":"2016","author":"Salvi","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1248\/bpb.33.556","article-title":"Buthionine sulfoximine promotes methylglyoxal-induced apoptotic cell death and oxidative stress in en-dothelial cells","volume":"33","author":"Takahashi","year":"2010","journal-title":"Biol. Pharm. Bull."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:40:07Z","timestamp":1760136007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":203,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cancers14061585"],"URL":"https:\/\/doi.org\/10.3390\/cancers14061585","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,21]]}}}