Gonadotoxic effects of busulfan in two strains of mice

Reprod Toxicol. 2016 Jan:59:31-9. doi: 10.1016/j.reprotox.2015.09.002. Epub 2015 Oct 30.

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.

Keywords: Busulfan; Fertility; Mice; Sperm morphology; Spermatogonial stem cell.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity*
  • Busulfan / toxicity*
  • Cell Shape / drug effects
  • Female
  • Fertility / drug effects*
  • Gene Expression Regulation, Developmental
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Infertility, Male / chemically induced*
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Infertility, Male / physiopathology
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Live Birth
  • Male
  • Mice, Inbred BALB C
  • Pregnancy
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Species Specificity
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects*
  • Spermatozoa / pathology
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology

Substances

  • Antineoplastic Agents, Alkylating
  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Kruppel-Like Transcription Factors
  • Nanos2 protein, mouse
  • Nanos3 protein, mouse
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA-Binding Proteins
  • Zbtb16 protein, mouse
  • Busulfan