title: Gonadotoxic effects of busulfan in two strains of mice.
abstract: Busulfan is a chemotherapy drug that has side effects on spermatogonial stem cells (SSC). The effects of bulsufan treatment on male germ cells and fertility vary significantly between individuals. In this study, we have used molecular, cellular and histopathology approaches to investigate the effects of a single intraperitoneal dose of busulfan (40mgkg(-1)) in two mice strains, Balb/C and Swiss, at two different periods after treatment, 30 and 90 days. Testicular degeneration was observed in both Balb/C and Swiss mice after busulfan injection. Interestingly, testicular functions and fertility recovered spontaneously post busulfan treatment in Swiss mice, but not in Balb/C mice. Abnormal fertility induced by busulfan in Balb/C mice was associated with altered seminiferous tubules, sperm morphology and transcript levels of Nanos2, Nanos3, Gdnf and Plzf genes. These findings revealed that SSC of Balb/C mice are more sensitive to the toxic effects of busulfan then those of Swiss mice.
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Gutierrez
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Werner G
authors.initials: WG
authors.lastname: Glanzner
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Raiza O
authors.initials: RO
authors.lastname: Chemeris
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Melânia L
authors.initials: ML
authors.lastname: Rigo
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil; Department of Clinical Medicine -Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Fabio V
authors.initials: FV
authors.lastname: Comim
authors.affiliation: Department of Animal Science, McGill University, 21,111 Lakeshore Road, Sainte-Anne-de-Bellevue, QC, H9X3V9 Canada. Electronic address: vilceu.bordignon@mcgill.ca.
authors.forename: Vilceu
authors.initials: V
authors.lastname: Bordignon
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil. Electronic address: bayard@ufsm.br.
authors.forename: Paulo B D
authors.initials: PB
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D002066:Busulfan / Q000633:toxicity*; D048430:Cell Shape / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D007248:Infertility, Male / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D050498:Live Birth; D008297:Male; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051741:Kruppel-Like Transcription Factors; C477341:Nanos2 protein, mouse; C477342:Nanos3 protein, mouse; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016601:RNA-Binding Proteins; C513267:Zbtb16 protein, mouse; D002066:Busulfan
keywords: Busulfan; Fertility; Mice; Sperm morphology; Spermatogonial stem cell