Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor

IntroductionTesticular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer fo...

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Autores: Farnetani G., Fino M.G., Cioppi F., Riera-Escamilla A., Tamburrino L., Vannucci M., Rosta V., Vinci S., Casamonti E., Turki L., Degl'Innocenti S., Spinelli M., Marchiani S., Lotti F., Muratori M., Krausz C.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p16118
Acesso em linha:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16118
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152008982&doi=10.1111%2fandr.13429&partnerID=40&md5=373e97b475e4be86379d9a0734a530f9
Access Level:acceso abierto
Palavra-chave:chemotherapy
cytotoxic therapy
sperm DNA fragmentation
spermatogenesis
testicular cancer
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spelling Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumorFarnetani G.Fino M.G.Cioppi F.Riera-Escamilla A.Tamburrino L.Vannucci M.Rosta V.Vinci S.Casamonti E.Turki L.Degl'Innocenti S.Spinelli M.Marchiani S.Lotti F.Muratori M.Krausz C.chemotherapycytotoxic therapysperm DNA fragmentationspermatogenesistesticular cancerIntroductionTesticular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods, and the large majority is limited to 2 years. ObjectiveTo define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage at 2 and 3 years from the end of therapy. Materials and methodsSperm DNA fragmentation was evaluated in 115 testicular germ cell tumor patients using terminal deoxynucleotidyl transferase dUTP nick end labeling assay coupled with flow cytometry before (T-0) and 2 (T-2) and 3 (T-3) years post-treatment. Patients were divided based on the type of treatment: carboplatin, bleomycin-etoposide-cisplatin, and radiotherapy. For 24 patients, paired sperm DNA fragmentation data were available at all time-points (T-0-T-2-T-3). Seventy-nine cancer-free, fertile normozoospermic men served as controls. Severe DNA damage was defined as the 95th percentile in controls (sperm DNA fragmentation = 50%). ResultsComparing patients versus controls, we observed: (i) no differences at T-0 and T-3 and (ii) significantly higher sperm DNA fragmentation levels (p < 0.05) at T-2 in all treatment groups. Comparing pre- and post-therapy in the 115 patients, the median sperm DNA fragmentation values were higher in all groups at T-2, reaching significance (p < 0.05) only in the carboplatin group. While the median sperm DNA fragmentation values were also higher in the strictly paired cohort at T-2, about 50% of patients returned to baseline. The proportion of severe DNA damage in the entire cohort was 23.4% and 4.8% of patients at T-2 and T-3, respectively. DiscussionCurrently, testicular germ cell tumor patients are advised to wait 2 years post-therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients. ConclusionThe analysis of sperm DNA fragmentation may represent a useful biomarker for pre-conception counseling following cancer treatment.WILEY2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16118https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152008982&doi=10.1111%2fandr.13429&partnerID=40&md5=373e97b475e4be86379d9a0734a530f9AndrologyISSN: 20472919ISSNe: 20472927reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p161182026-06-14T12:41:47Z
dc.title.none.fl_str_mv Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
title Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
spellingShingle Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
Farnetani G.
chemotherapy
cytotoxic therapy
sperm DNA fragmentation
spermatogenesis
testicular cancer
title_short Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
title_full Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
title_fullStr Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
title_full_unstemmed Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
title_sort Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
dc.creator.none.fl_str_mv Farnetani G.
Fino M.G.
Cioppi F.
Riera-Escamilla A.
Tamburrino L.
Vannucci M.
Rosta V.
Vinci S.
Casamonti E.
Turki L.
Degl'Innocenti S.
Spinelli M.
Marchiani S.
Lotti F.
Muratori M.
Krausz C.
author Farnetani G.
author_facet Farnetani G.
Fino M.G.
Cioppi F.
Riera-Escamilla A.
Tamburrino L.
Vannucci M.
Rosta V.
Vinci S.
Casamonti E.
Turki L.
Degl'Innocenti S.
Spinelli M.
Marchiani S.
Lotti F.
Muratori M.
Krausz C.
author_role author
author2 Fino M.G.
Cioppi F.
Riera-Escamilla A.
Tamburrino L.
Vannucci M.
Rosta V.
Vinci S.
Casamonti E.
Turki L.
Degl'Innocenti S.
Spinelli M.
Marchiani S.
Lotti F.
Muratori M.
Krausz C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv chemotherapy
cytotoxic therapy
sperm DNA fragmentation
spermatogenesis
testicular cancer
topic chemotherapy
cytotoxic therapy
sperm DNA fragmentation
spermatogenesis
testicular cancer
description IntroductionTesticular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods, and the large majority is limited to 2 years. ObjectiveTo define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage at 2 and 3 years from the end of therapy. Materials and methodsSperm DNA fragmentation was evaluated in 115 testicular germ cell tumor patients using terminal deoxynucleotidyl transferase dUTP nick end labeling assay coupled with flow cytometry before (T-0) and 2 (T-2) and 3 (T-3) years post-treatment. Patients were divided based on the type of treatment: carboplatin, bleomycin-etoposide-cisplatin, and radiotherapy. For 24 patients, paired sperm DNA fragmentation data were available at all time-points (T-0-T-2-T-3). Seventy-nine cancer-free, fertile normozoospermic men served as controls. Severe DNA damage was defined as the 95th percentile in controls (sperm DNA fragmentation = 50%). ResultsComparing patients versus controls, we observed: (i) no differences at T-0 and T-3 and (ii) significantly higher sperm DNA fragmentation levels (p < 0.05) at T-2 in all treatment groups. Comparing pre- and post-therapy in the 115 patients, the median sperm DNA fragmentation values were higher in all groups at T-2, reaching significance (p < 0.05) only in the carboplatin group. While the median sperm DNA fragmentation values were also higher in the strictly paired cohort at T-2, about 50% of patients returned to baseline. The proportion of severe DNA damage in the entire cohort was 23.4% and 4.8% of patients at T-2 and T-3, respectively. DiscussionCurrently, testicular germ cell tumor patients are advised to wait 2 years post-therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients. ConclusionThe analysis of sperm DNA fragmentation may represent a useful biomarker for pre-conception counseling following cancer treatment.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16118
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152008982&doi=10.1111%2fandr.13429&partnerID=40&md5=373e97b475e4be86379d9a0734a530f9
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16118
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152008982&doi=10.1111%2fandr.13429&partnerID=40&md5=373e97b475e4be86379d9a0734a530f9
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv Andrology
ISSN: 20472919
ISSNe: 20472927
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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