{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:59:27Z","timestamp":1778813967391,"version":"3.51.4"},"reference-count":113,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Whilst chemotherapy regimens have proven to be more successful for pediatric cancer patients over the years, their influence on long\u2010term side effects is relatively poorly understood. One of the possible targets is the gonads, with gonadotoxic agents representing those that threaten the patient's ability to have children post surviving the primary disease treatment. Many risk stratification guidelines have categorized these agents based on the severity of their effect on the pre\u2010pubertal testis. While the consensus is that those agents factored with a cyclophosphamide equivalent dosage pose the highest threat to fertility (e.g. alkylating agents), other agents might still contribute to a reduced testis function; especially in the case of combination therapies. Besides, it is important to note that studies deciphering the effect of other non\u2010alkylating agents on the pre\u2010pubertal testis lack standardized conclusions for clinically relevant outcomes. This makes it imperative to ensure the knowledge gap is addressed between the clinic and pre\u2010clinic to understand potential gonadotoxic effects, ultimately leading to improved patient care. Therefore, this review will summarize the key findings in understanding the gonadotoxic effects of the most commonly researched non\u2010alkylating agents: vincristine, etoposide, doxorubicin, and imatinib on the pre\u2010pubertal testis.<\/jats:p>","DOI":"10.1111\/cts.70075","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T07:45:54Z","timestamp":1732520754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non\u2010alkylating agents\u2010induced gonadotoxicity in pre\u2010pubertal males: Insights on the clinical and pre\u2010clinical front"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-0440","authenticated-orcid":false,"given":"Sruthi","family":"Sriram","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-6053","authenticated-orcid":false,"given":"Tiago","family":"Macedo","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-3626","authenticated-orcid":false,"given":"Annelies","family":"Mavinkurve\u2010Groothuis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-3032","authenticated-orcid":false,"given":"Marianne","family":"van de Wetering","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8146-1911","authenticated-orcid":false,"given":"Leendert H. J.","family":"Looijenga","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27297"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030745"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041454"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30582-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24679"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13866"},{"key":"e_1_2_8_8_1","volume-title":"Childhood Cancer and Functional Impacts across the Care Continuum","author":"Aiuppa L","year":"2020"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.20045"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gap024"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-006-0168-3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927608080318"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0801-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.8.5453"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1366"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1367"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601811200"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-07-0536"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-151555"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155420916274"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.1040"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(98)00036-0"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061404598"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2008.10.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19761-9"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00302383"},{"issue":"17","key":"e_1_2_8_28_1","first-page":"6423","article-title":"Amifostine protects against early but not late toxic effects of doxorubicin in infant rats","volume":"61","author":"Jahnukainen K","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-10-79"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.279"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2018.04.014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-8-3"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1535"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2020.12.023"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000365727"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678-4324-2019180017"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22384"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.08.060"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/6535"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1159\/000079138"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2019.02.018"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2010.12.056"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.2.689"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1080420307"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2007.00755.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0349"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.33899\/ijvs.2020.126342.1303"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod57.3.676"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2008.03.004"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1372643"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.83107"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2021.100527"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-17-0005"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74862-8"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-11286-6"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.33448\/rsd-v11i3.26121"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1071\/rd05065"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.22034\/APJCP.2018.19.3.683"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2608"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043364531"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981115)83:10<2217::AID-CNCR22>3.0.CO;2-J"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-013-1527-9"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.2.387"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dei416"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.6.1204"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03346719"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006647.pub4"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.uct.2006.04.001"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c180017"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-5347(17)51579-7"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.2.239"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19921201)70:11<2703::aid-cncr2820701123>3.0.co;2-x"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228529"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00977-0"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25792"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.2147\/BTT.S5775"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.82.12.4449"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200411113512024"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.08.060"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13554-4"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-017-0521-6"},{"issue":"11","key":"e_1_2_8_82_1","first-page":"1231","article-title":"Vinca alkaloids","volume":"4","author":"Moudi M","year":"2013","journal-title":"Int J Prev Med"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.12.4143"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2012.02.011"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmac039"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)92301-1"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep-08-0096"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359221113274"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-2042.2001.00382.x"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867322666150821094334"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12426"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20693"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des159"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690761"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27729"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08879-x"},{"key":"e_1_2_8_98_1","unstructured":"European Medicines Agency.ICH S5 (R3) guideline on detection of reproductive and developmental toxicity for human pharmaceuticals \u2010 step 5 \u2010 Revision 4.2020.https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/ich\u2010s5\u2010r3\u2010guideline\u2010detection\u2010reproductive\u2010and\u2010developmental\u2010toxicity\u2010human\u2010pharmaceuticals\u2010step\u20105\u2010revision\u20104_en.pdf"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2018.04.009"},{"issue":"1","key":"e_1_2_8_100_1","first-page":"28","article-title":"Is the testis a chemo\u2010privileged site? Is there a blood\u2010testis barrier?","volume":"9","author":"Dave DS","year":"2007","journal-title":"Rev Urol"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gay012"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.041335"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1994.tb00468.x"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-7992(93)90077-9"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-005-1382-0"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12740"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2317"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.3389\/frph.2022.812053"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaw051"},{"key":"e_1_2_8_110_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.1585"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdaa075"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12283"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23074013"},{"key":"e_1_2_8_114_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00357-6"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T07:17:44Z","timestamp":1732605464000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":113,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/cts.70075"],"URL":"https:\/\/doi.org\/10.1111\/cts.70075","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70075"}}