{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:12:32Z","timestamp":1788023552838,"version":"build-2784847793"},"reference-count":58,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011733","name":"Portuguese League Against Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Reproductive Toxicology"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1016\/j.reprotox.2024.108721","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T19:48:54Z","timestamp":1727207334000},"page":"108721","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["A systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility"],"prefix":"10.1016","volume":"130","author":[{"given":"Ana Lobo","family":"de Almeida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fortuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rio","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ros\u00e1lia","family":"S\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA\u00a0Cancer J. Clin."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"Ca. Cancer J. Clin."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108721_bib3","first-page":"579","article-title":"Impact of cancer and cancer treatment on male fertility","volume":"14","author":"Vakalopoulos","year":"2015","journal-title":"Hormones"},{"issue":"5","key":"10.1016\/j.reprotox.2024.108721_bib4","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.fertnstert.2021.03.026","article-title":"Fertility preservation in men: a contemporary overview and a look toward emerging technologies","volume":"115","author":"Brannigan","year":"2021","journal-title":"Fertil. Steril."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108721_bib5","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/humupd\/7.4.363","article-title":"Testicular function following chemotherapy","volume":"7","author":"Howell","year":"2001","journal-title":"Hum. Reprod. Update"},{"issue":"S10","key":"10.1016\/j.reprotox.2024.108721_bib6","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1002\/cncr.26045","article-title":"Oncofertility and preservation of reproductive capacity in children and young adults","volume":"117","author":"Wallace","year":"2011","journal-title":"Cancer"},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib7","doi-asserted-by":"crossref","DOI":"10.1002\/rmb2.12481","article-title":"Fertility and sexual dysfunction in young male cancer survivors","volume":"21","author":"Yumura","year":"2022","journal-title":"Reprod. Med. Biol."},{"issue":"34","key":"10.1016\/j.reprotox.2024.108721_bib8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/jncimonographs\/lgi003","article-title":"Spermatogenesis after cancer treatment: damage and recovery","volume":"2005","author":"Howell","year":"2005","journal-title":"J. Natl. Cancer Inst. Monogr."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108721_bib9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s11864-012-0191-7","article-title":"Oncofertility and the male cancer patient","volume":"13","author":"Trost","year":"2012","journal-title":"Curr. Treat. Options Oncol."},{"key":"10.1016\/j.reprotox.2024.108721_bib10","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/1097-0142(1967)20:5<891::AID-CNCR2820200550>3.0.CO;2-V","article-title":"Studies on bleomycin","volume":"20","author":"Umezawa","year":"1967","journal-title":"Cancer"},{"key":"10.1016\/j.reprotox.2024.108721_bib11","unstructured":"J.P. Brandt, V. Gerriets, Bleomycin, in: StatPearls [Internet]. StatPearls, Treasure Island(FL), 2020."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/annonc\/mdg020","article-title":"Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours","volume":"14","author":"O\u2019Sullivan","year":"2003","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.reprotox.2024.108721_bib13","first-page":"39","article-title":"Bleomycin","volume":"18","author":"Lazo","year":"1999","journal-title":"Cancer Chemother. Biol. Response Modif."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108721_bib14","first-page":"3618","article-title":"Bleomycin: an overview on anti-cancer drug","volume":"5","author":"Rahaman","year":"2018","journal-title":"Int. J. Recent Adv. Multi. Res."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108721_bib15","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.3892\/ijo.2012.1668","article-title":"Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1","volume":"41","author":"Chen","year":"2012","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.reprotox.2024.108721_bib16","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.phrs.2015.04.012","article-title":"Bleomycin in the setting of lung fibrosis induction: from biological mechanisms to counteractions","volume":"97","author":"Della Latta","year":"2015","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.reprotox.2024.108721_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/480608","article-title":"Bleomycin-induced lung injury","volume":"2013","author":"Reinert","year":"2013","journal-title":"Cancer Res."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib18","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4997\/JRCPE.2010.306","article-title":"Toxicities associated with bleomycin","volume":"40","author":"Fyfe","year":"2010","journal-title":"J. R. Coll. Physicians Edinb."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108721_bib19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jrsm.1378","article-title":"Which academic search systems are suitable for systematic reviews or meta-analyses? Evaluating retrieval qualities of google scholar, pubmed, and 26 other resources","volume":"11","author":"Gusenbauer","year":"2020","journal-title":"Res. Synth. Methods"},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib20","first-page":"21","article-title":"Induction of apoptosis by bleomycin compound in testis of Swiss albino mice","volume":"19","author":"Ojo","year":"2017","journal-title":"AIJRFANS"},{"issue":"9","key":"10.1016\/j.reprotox.2024.108721_bib21","first-page":"3575","article-title":"Cytotoxic effects of chemotherapeutic drugs on mouse testis cells","volume":"39","author":"Lu","year":"1979","journal-title":"Cancer Res."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108721_bib22","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0022-4731(88)90140-9","article-title":"Effects of cisplatin and bleomycin on mature rat Leydig cell testosterone production","volume":"30","author":"Carreau","year":"1988","journal-title":"J. Steroid Biochem."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib23","first-page":"209","article-title":"Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-\u200e induced male rats, Iran.","volume":"12","author":"Amirshahi","year":"2014","journal-title":"J. Reprod. Med."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108721_bib24","first-page":"112","article-title":"Valsartan attenuated bleomycin-induced male rat reproductive toxicity","volume":"2","author":"Thwaini","year":"2015","journal-title":"Eur. J. Biomed. Pharm. Sci."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib25","doi-asserted-by":"crossref","first-page":"246","DOI":"10.17094\/ataunivbd.563809","article-title":"Changes in sperm parameters following administration of theophylline, a competitive antagonist of adenosine in rats exposed to bleomycin, a chemotherapeutic agent","volume":"14","author":"Belhan","year":"2019","journal-title":"Atat\u00fcrk \u00dcniversitesi Vet. Bilim. Derg."},{"issue":"12S","key":"10.1016\/j.reprotox.2024.108721_bib26","doi-asserted-by":"crossref","first-page":"S611","DOI":"10.1177\/09603271211048184","article-title":"Thymoquinone ameliorates bleomycin-induced reproductive toxicity in male Balb\/c mice","volume":"40","author":"Yaghutian Nezhad","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"issue":"25","key":"10.1016\/j.reprotox.2024.108721_bib27","first-page":"433","article-title":"Ameliorative effects of vitamin E and selenium on bleomycin-induced male infertility","volume":"60","author":"Ibrahim","year":"2023","journal-title":"Slov. Vet. Res."},{"key":"10.1016\/j.reprotox.2024.108721_bib28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.theriogenology.2019.09.039","article-title":"Protective effects of zinc on rat sperm chromatin Integrity involvement: DNA methylation, DNA fragmentation, ubiquitination, and protamination after bleomycin etoposide and cis-platin treatment","volume":"142","author":"Khadivi","year":"2020","journal-title":"Theriogenology"},{"key":"10.1016\/j.reprotox.2024.108721_bib29","unstructured":"ICH, Detection of toxicity to reproduction for medicinal products and toxicity to male fertility S5 (R2), in: ICH Harmonised Tripartite Guideline (2005)."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108721_bib30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/01926230290105695","article-title":"Recommended approaches for the evaluation of testicular and epididymal toxicity","volume":"30","author":"Lanning","year":"2002","journal-title":"Toxicol. Pathol."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib31","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/humrep\/del279","article-title":"Histological evaluation of the human testis - approaches to optimizing the clinical value of the assessment: mini review","volume":"22","author":"McLachlan","year":"2007","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.reprotox.2024.108721_bib32","series-title":"WHO laboratory manual for the examination and processing of human semen. (5th ed.)","author":"WHO","year":"2010"},{"key":"10.1016\/j.reprotox.2024.108721_bib33","series-title":"WHO laboratory manual for the examination and processing of human semen. (6th ed.)","author":"WHO","year":"2021"},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-017-0664-4","article-title":"The role of cellular reactive oxygen species in cancer chemotherapy","volume":"37","author":"Yang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108721_bib35","first-page":"493","article-title":"Role of sperm apoptosis and oxidative stress in male infertility: a narrative review","volume":"19","author":"Asadi","year":"2021","journal-title":"Int. J. Reprod. Biomed."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib36","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.urology.2014.05.016","article-title":"Seminal BAX and BCL2 gene and protein expressions in infertile men with varicocele","volume":"84","author":"Mostafa","year":"2014","journal-title":"Urology"},{"key":"10.1016\/j.reprotox.2024.108721_bib37","doi-asserted-by":"crossref","unstructured":"R. Sharma, A. Agarwal, Spermatogenesis: An Overview, in: A. Zini, A. Agarwal, Sperm Chromatin (pp. 19-44), Springer, New York, 2011.","DOI":"10.1007\/978-1-4419-6857-9_2"},{"key":"10.1016\/j.reprotox.2024.108721_bib38","unstructured":"P. Gurung, E. Yetiskul, I. Jialal, Physiology, Male Reproductive System, in: StatPearls [Internet], Stat Pearls, Treasure Island(FL), 2022."},{"key":"10.1016\/j.reprotox.2024.108721_bib39","series-title":"Principles of Endocrinology and Hormone Action. Endocrinology","first-page":"455","article-title":"The physiology of the testis","author":"Ilacqua","year":"2018"},{"issue":"2","key":"10.1016\/j.reprotox.2024.108721_bib40","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/pbc.22000","article-title":"Normal testicular function and spermatogenesis","volume":"53","author":"Shalet","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"10.1016\/j.reprotox.2024.108721_bib41","unstructured":"North Bristol NHS Trust, Blood Sciences: Age-related reference ranges. \u3008https:\/\/www.nbt.nhs.uk\/sites\/default\/files\/document\/Biochemistry%20Age%20Related%20Reference%20Ranges.pdf\u3009, 2022."},{"key":"10.1016\/j.reprotox.2024.108721_bib42","unstructured":"Rocky Mountain Diagnostics, Inc, Testosterone rat: Mouse ELISA instruction. \u3008https:\/\/rmdiagnostics.com\/testosterone-rat-mouse-elisa-instruction\/\u3009, 2023."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108721_bib43","doi-asserted-by":"crossref","DOI":"10.4161\/21565562.2014.979099","article-title":"Morphologic manifestations of testicular and epididymal toxicity","volume":"4","author":"Vidal","year":"2014","journal-title":"Spermatogenesis"},{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib44","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.reprotox.2006.03.017","article-title":"Tertiary-butyl hydroperoxide induced oxidative stress and male reproductive activity in mice: role of transcription factor NF-kappaB and testicular antioxidant enzymes","volume":"22","author":"Kaur","year":"2006","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2024.108721_bib45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clinbiochem.2021.03.008","article-title":"Are antioxidant enzymes essential markers in the diagnosis and monitoring of cancer patients \u2013 a review","volume":"93","author":"Cecerska-Hery\u0107","year":"2021","journal-title":"Clin. Biochem."},{"issue":"3","key":"10.1016\/j.reprotox.2024.108721_bib46","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1179\/174329211X13049558293551","article-title":"Unbalanced oxidant-antioxidant status and its effects in pediatric diseases","volume":"16","author":"Chiavaroli","year":"2011","journal-title":"Redox Rep."},{"issue":"2","key":"10.1016\/j.reprotox.2024.108721_bib47","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/2090598X.2019.1599624","article-title":"Oxidative stress and sperm function: a systematic review on evaluation and management","volume":"17","author":"Dutta","year":"2019","journal-title":"Arab. J. Urol."},{"issue":"4","key":"10.1016\/j.reprotox.2024.108721_bib48","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/10408347.2012.751786","article-title":"An overview of the Kjeldahl method of nitrogen determination. part i. early history, chemistry of the procedure, and titrimetric finish","volume":"43","author":"S\u00e1ez-Plaza","year":"2013","journal-title":"Crit. Rev. Anal. Chem."},{"key":"10.1016\/j.reprotox.2024.108721_bib49","doi-asserted-by":"crossref","DOI":"10.1186\/s12610-018-0082-2","article-title":"Protective role of N-acetylcysteine (NAC) on human sperm exposed to etoposide","volume":"29","author":"Baetas","year":"2019","journal-title":"Basic Clin. Androl."},{"issue":"10","key":"10.1016\/j.reprotox.2024.108721_bib50","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3390\/antiox8100449","article-title":"Cancer chemotherapy and chemiluminescence detection of reactive oxygen species in human semen","volume":"8","author":"Takeshima","year":"2019","journal-title":"Antioxidants"},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib51","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11095-019-2745-x","article-title":"Intraperitoneal route of drug administration: Should it be used in experimental animal studies?","volume":"37","author":"Al Shoyaib","year":"2020","journal-title":"Pharm. Res."},{"key":"10.1016\/j.reprotox.2024.108721_bib52","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3389\/fmed.2018.00269","article-title":"Bleomycin revisited: a direct comparison of the intratracheal micro-spraying and the oropharyngeal aspiration routes of bleomycin administration in mice","volume":"5","author":"Barbayianni","year":"2018","journal-title":"Front. Med."},{"issue":"6","key":"10.1016\/j.reprotox.2024.108721_bib53","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/bdrb.20338","article-title":"Incidence and nature of testicular toxicity findings in pharmaceutical development","volume":"92","author":"Sasaki","year":"2011","journal-title":"Birth Defects Res. B. Dev. Reprod. Toxicol."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib54","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1080\/019262301301418865","article-title":"Pathogenesis of male reproductive toxicity","volume":"29","author":"Creasy","year":"2001","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.reprotox.2024.108721_bib55","doi-asserted-by":"crossref","unstructured":"B.B. Chen, B.R. Zirkin, R.S. Ge, Reproductive and Endocrine Toxicology. Elsevier Inc.; Amsterdam, The Netherlands: 2018. The Leydig Cell as a Target for Toxicants, pp. 96\u2013111.","DOI":"10.1016\/B978-0-08-100601-6.01108-X"},{"issue":"4","key":"10.1016\/j.reprotox.2024.108721_bib56","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.rbmo.2015.06.019","article-title":"Sperm DNA fragmentation is related to sperm morphological staining patterns","volume":"31","author":"S\u00e1","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"10.1016\/j.reprotox.2024.108721_bib57","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1289\/ehp.887737","article-title":"Male reproductive toxicology: comparison of the human to animal models","volume":"77","author":"Working","year":"1988","journal-title":"Environ. Health Perspect."},{"issue":"1","key":"10.1016\/j.reprotox.2024.108721_bib58","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3390\/life12010048","article-title":"Comparison of anticancer drug toxicities: paradigm shift in adverse effect profile","volume":"12","author":"Basak","year":"2021","journal-title":"Life"}],"container-title":["Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0890623824001886?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0890623824001886?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T21:47:55Z","timestamp":1733348875000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0890623824001886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":58,"alternative-id":["S0890623824001886"],"URL":"https:\/\/doi.org\/10.1016\/j.reprotox.2024.108721","relation":{},"ISSN":["0890-6238"],"issn-type":[{"value":"0890-6238","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility","name":"articletitle","label":"Article Title"},{"value":"Reproductive Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.reprotox.2024.108721","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"108721"}}