Amifostine-doxorubicin association causes long-term prepubertal spermatogonia DNA damage and early developmental arrest

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dc.contributor.authorVendramini, V. [UNIFESP]
dc.contributor.authorRobaire, B.
dc.contributor.authorMiraglia, S. M. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionMcGill Univ
dc.date.accessioned2016-01-24T14:27:29Z
dc.date.available2016-01-24T14:27:29Z
dc.date.issued2012-08-01
dc.description.abstractIn a previous study, we found that amifostine provides some protection to the seminiferous epithelium of prepubertal doxorubicin-treated male rats but does not improve their fertility status as adults. Based on these results, a long-term study was undertaken to evaluate the DNA damage caused to spermatogonia and the consequences for embryo development.Twenty-four male prepubertal rats (30-day-old) were divided into four equal groups and treated with: doxorubicin (D5 mg/kg), amifostine (A400 mg/kg), amifostine/doxorubicin (ADamifostine 15 min before doxorubicin) and control (C0.9 saline solution). Sixty-four days after the treatment, animals were euthanized and the testes and epididymides were excised. the testes were fixed in Bouins solution and historesin-embedded for histopathological analysis. Spermatozoa from the cauda epididymides were collected for chromatin structure analyses (Comet Assay and SCSA). Adult rats (100-day-old) were mated with fertile females for embryo analyses on 2.5, 4.5 and 20 days post-coitum (d.p.c.).The seminiferous epithelium histopathology of AD group was better preserved compared with the D group. On the other hand, rats from the D and AD groups presented an increased percentage of sperm DNA strand breaks, as assessed by the comet assay, as well as an increased level of sperm chromatin denaturation, as assessed by the SCSA assay. in amifostine-treated groups (A and AD) there was a significant increase in the number of arrested embryos, as observed by the number of oocytes/zygotes on 2.5 d.p.c., when compared with control and doxorubicin groups; however, this number was increased when the AD group was compared with the A group.These results raise a concern about the effects of the association of these two drugs on the germ cell genome. Amifostinedoxorubicin-exposed rat spermatogonia produced long-term damage on sperm DNA, compromised conceptus development and reduced pregnancy outcome.en
dc.description.affiliationFed Univ São Paulo UNIFESP, Dept Morphol & Genet, Dev Biol Lab, São Paulo, Brazil
dc.description.affiliationMcGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada
dc.description.affiliationMcGill Univ, Dept Obstet & Gynecol, Montreal, PQ H3A 2T5, Canada
dc.description.affiliationUnifespFed Univ São Paulo UNIFESP, Dept Morphol & Genet, Dev Biol Lab, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent2457-2466
dc.identifierhttp://dx.doi.org/10.1093/humrep/des159
dc.identifier.citationHuman Reproduction. Oxford: Oxford Univ Press, v. 27, n. 8, p. 2457-2466, 2012.
dc.identifier.doi10.1093/humrep/des159
dc.identifier.issn0268-1161
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35103
dc.identifier.wosWOS:000306648600026
dc.language.isoeng
dc.publisherOxford Univ Press
dc.relation.ispartofHuman Reproduction
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html
dc.subjectamifostineen
dc.subjectdoxorubicinen
dc.subjectmale fertilityen
dc.subjectsperm integrityen
dc.subjectpreimplantation embryoen
dc.titleAmifostine-doxorubicin association causes long-term prepubertal spermatogonia DNA damage and early developmental arresten
dc.typeinfo:eu-repo/semantics/article
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