title: Characterization of a mechanism to inhibit ovarian follicle activation.
abstract: OBJECTIVE
  To demonstrate that a small molecule can induce the transcription factor Foxo3 in the ovary and lead to inhibition of follicle activation.
  
  
  METHODS
  Cell culture, organ culture, and animal studies.
  
  
  METHODS
  University-based laboratory.
  
  
  METHODS
  23 female C57BL/6 mice.
  
  
  METHODS
  Human ovary cells and mouse ovaries in culture treated with 2-deoxyglucose (2-DG) to mimic glucose deprivation, and mice intraperitoneally injected with 100 mg/kg, 300 mg/kg, or 600 mg/kg 2-DG daily for 2 weeks.
  
  
  METHODS
  In cell and organ culture, Foxo3 expression analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR); in treated animals, expression of genes regulated by nutrient deprivation (Foxo3, ATF4, GRP78, CHOP, ASNS, c-Myc) measured in brain, kidney, and ovary by qRT-PCR; and ovarian follicles histologically classified and counted.
  
  
  RESULTS
  Foxo3 expression is induced by 2-DG at both the mRNA and protein level in human ovarian cell culture, possibly through ATF4-dependent gene regulation. Foxo3 expression is also induced by 2-DG in ovarian organ culture. Treatment of mice with 100 mg/kg 2-DG resulted in a 2.6 fold induction of Foxo3 in the ovary and a 58% decrease in type 3a primary follicles.
  
  
  CONCLUSIONS
  Expression of Foxo3 is induced by nutrient deprivation in cell culture, organ culture, and in vivo. In mice, 2-DG treatment results in an inhibition of primordial follicle activation. These data indicate that Foxo3 induction by 2-DG may be useful for fertility preservation.
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida; Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Barilovits
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Newsom
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Bickford
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Beachy
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Alice
authors.initials: A
authors.lastname: Rhoton-Vlasak
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida; Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida. Electronic address: hnick@ufl.edu.
authors.forename: Harry S
authors.initials: HS
authors.lastname: Nick
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D003847:Deoxyglucose
keywords: 2-Deoxyglucose; Foxo3; follicle activation; nutrient deprivation; ovarian reserve