title: Granulocyte colony-stimulating factor prevents loss of spermatogenesis after sterilizing busulfan chemotherapy.
abstract: OBJECTIVE
  To determine whether granulocyte colony-stimulating factor (G-CSF) could prevent loss of spermatogenesis induced by busulfan chemotherapy via protection of undifferentiated spermatogonia, which might serve as an adjuvant approach to preserving male fertility among cancer patients.
  
  
  METHODS
  Laboratory animal study.
  
  
  METHODS
  University.
  
  
  METHODS
  Laboratory mice.
  
  
  METHODS
  Five-week-old mice were treated with a sterilizing busulfan dose and with 7 days of G-CSF or vehicle treatment and evaluated 10 weeks later (experiment 1) or 24 hours after treatment (experiment 2).
  
  
  METHODS
  Experiment 1: testis weights, epididymal sperm counts, testis histology. Experiment 2: PLZF immunofluorescent costaining with apoptotic markers. Molecular analysis of G-CSF receptor expression in undifferentiated spermatogonia.
  
  
  RESULTS
  Ten weeks after treatment, busulfan-treated mice that also received treatment with G-CSF exhibited significantly better recovery of spermatogenesis and epididymal sperm counts than animals receiving busulfan alone. G-CSF led to increased numbers of PLZF+ spermatogonia 24 hours after treatment that was not accompanied by changes in apoptosis. To address the cellular target of G-CSF, mRNA for the G-CSF receptor, Csf3r, was found in adult mouse testes and cultured THY1+ (undifferentiated) spermatogonia, and cell-surface localized CSF3R was observed on 3% of cultured THY1+ spermatogonia.
  
  
  CONCLUSIONS
  These results demonstrate that G-CSF protects spermatogenesis from gonadotoxic insult (busulfan) in rodents, and this may occur via direct action on CSF3R+ undifferentiated spermatogonia. G-CSF treatment might be an effective adjuvant therapy to preserve male fertility in cancer patients receiving sterilizing treatments.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Roberto
authors.initials: R
authors.lastname: Benavides-Garcia
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Rose
authors.initials: R
authors.lastname: Joachim
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Pina
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Kazadi N
authors.initials: KN
authors.lastname: Mutoji
authors.affiliation: Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Reilly
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, Texas. Electronic address: brian.hermann@utsa.edu.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Hermann
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D002066:Busulfan / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D059247:Fertility Preservation / Q000379:methods*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007248:Infertility, Male / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013091:Spermatogenesis / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016179:Granulocyte Colony-Stimulating Factor; D002066:Busulfan
keywords: Spermatogonial stem cells; cancer therapy; cytokines; fertility preservation; infertility