title: Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9.
abstract: BACKGROUND
  The signals initiating growth of primordial follicles are unknown. Bone morphogenetic protein 15 (BMP15) and growth differentiating factor 9 (GDF9) are promising candidates.
  
  
  OBJECTIVE
  The objective of the study was to evaluate for the first time the effects of human recombinant BMP15 and human recombinant GDF9 on the in vitro development of human primordial follicles.
  
  
  METHODS
  This was a controlled culture study performed in a major tertiary university-affiliated medical center.
  
  
  METHODS
  Materials included ovarian tissue from 17 girls/women and three aborted human fetuses.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  Histological and immunohistochemical (proliferating cell nuclear antigen, BMP15, and GDF9) studies and an endocrine assay of 17β-estradiol were conducted.
  
  
  RESULTS
  In the samples from girls/women, the number of developing follicles was greater with GDF9 or BMP15 alone than with no BMP15 or GDF9. Higher 17β-estradiol secretion was noted after treatment with GDF9 than with BMP15 or with GDF9+anti-GDF9. The number of atretic follicles was greater with BMP15 than with GDF9. Proliferating cell nuclear antigen expression was greater with the higher dose of both growth factors than the lower dose. Expression of BMP15 and GDF9 was identified in samples cultured without BMP15 or GDF9. Results for the fetal follicles yielded no distinguishable pattern.
  
  
  CONCLUSIONS
  Although both BMP15 and GDF9 promoted activation of human primordial follicles from girls/women (but not human fetuses) in a dose-dependent manner, GDF9 seems more beneficial.
authors.affiliation: Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 49100, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Kedem
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fisch
authors.forename: Roni
authors.initials: R
authors.lastname: Garor
authors.forename: Adi
authors.initials: A
authors.lastname: Ben-Zaken
authors.forename: Taya
authors.initials: T
authors.lastname: Gizunterman
authors.forename: Carmela
authors.initials: C
authors.lastname: Felz
authors.forename: Avi
authors.initials: A
authors.lastname: Ben-Haroush
authors.forename: Dragan
authors.initials: D
authors.lastname: Kravarusic
authors.forename: Ronit
authors.initials: R
authors.lastname: Abir
mesh_terms: D037881:Aborted Fetus / Q000502:physiology; D000293:Adolescent; D000328:Adult; D055430:Bone Morphogenetic Protein 15 / Q000494:pharmacology / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D005260:Female; D055429:Growth Differentiation Factor 9 / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009924:Organ Culture Techniques / Q000379:methods; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D011994:Recombinant Proteins; D004958:Estradiol