title: Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy.
abstract: OBJECTIVE
  To examine gonadal protective properties of granulocyte colony-stimulating factor (G-CSF) alone or in combination with stem cell factor (SCF) in female mice treated with high-dose alkylating chemotherapy.
  
  
  METHODS
  Experimental laboratory animal study.
  
  
  METHODS
  Tertiary care academic hospital and research institute.
  
  
  METHODS
  Six- and 8-week-old C57Bl/6 female mice.
  
  
  METHODS
  Adult female mice were treated with [1] cyclophosphamide and busulfan (CTx), [2] CTx + G-CSF/SCF, [3] CTx + G-CSF, or [4] normal saline and dimethyl sulfoxide (DMSO; vehicle control).
  
  
  METHODS
  Follicle counts, microvessel density, cellular response to DNA damage, and litter production.
  
  
  RESULTS
  G-CSF ± SCF increased microvessel density and decreased follicle loss in CTx-treated female mice compared with CTx-only treated female mice. Mice administered CTx alone exhibited premature ovarian insufficiency, with only 28% of mice producing two litters. However, 100% of mice receiving CTx with G-CSF + SCF, and 80% of mice receiving CTx + G-CSF alone produced at least three litters and 20% of mice in each group produced five litters.
  
  
  CONCLUSIONS
  Treatment of mice with G-CSF decreases chemotherapy-induced ovarian follicle loss and extends time to premature ovarian insufficiency in female mice. Further studies are needed to validate these preclinical results in humans and compare efficacy with the established GnRH analogue treatments.
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA.
authors: Malgorzata E
authors: ME
authors: Skaznik-Wikiel
authors: Megan M
authors: MM
authors: McGuire
authors: Meena
authors: M
authors: Sukhwani
authors: Julia
authors: J
authors: Donohue
authors: Tianjiao
authors: T
authors: Chu
authors: Thomas C
authors: TC
authors: Krivak
authors: Aleksandar
authors: A
authors: Rajkovic
authors: Kyle E
authors: KE
authors: Orwig
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D002066:Busulfan; D003520:Cyclophosphamide; D004249:DNA Damage; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005300:Fertility Agents, Female / Q000494:pharmacology*; D059247:Fertility Preservation / Q000379:methods*; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D007247:Infertility, Female / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008098:Litter Size / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000503:physiopathology; D010053:Ovary / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D010298:Parity / Q000187:drug effects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002066:Busulfan; D003520:Cyclophosphamide; D005300:Fertility Agents, Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor; D006657:Histones; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C475961:gamma-H2AX protein, mouse