title: Inhibitors of c-Jun phosphorylation impede ovine primordial follicle activation.
abstract: Is the c-Jun-N-terminal kinase (JNK) pathway implicated in primordial follicle activation?
  
  
  
  Culture of ovine ovarian cortex in the presence of two different c-Jun phosphorylation inhibitors impeded pre-antral follicle activation.
  
  
  
  Despite its importance for fertility preservation therapies, the mechanisms of primordial follicle activation are poorly understood. Amongst different signalling pathways potentially involved, the JNK pathway has been previously shown to be essential for cell cycle progression and pre-antral follicle development in mice.
  
  
  
  Ovine ovarian cortex pieces were cultured with varying concentrations of SP600125, JNK inhibitor VIII or anti-Mullerian hormone (AMH) in the presence of FSH for 9 days. Follicular morphometry and immunohistochemistry for proliferating cell nuclear antigen (PCNA), apoptosis and follicle activation (Foxo3a) were assessed.
  
  
  
  Inhibition of primordial follicle activation occurred in the presence of SP600125, JNK inhibitor VIII and AMH when compared with controls (all P < 0.05) after 2 days of culture. However, only in the highest concentrations used was the inhibition of activation associated with induction of follicular apoptosis (P < 0.05). In growing follicles, PCNA antigen expression was reduced when the JNK inhibitors or AMH were used (P < 0.05 versus control), indicating reduced proliferation of the somatic compartment.
  
  
  
  Although we evaluated the effects of inhibition of c-Jun phosphorylation on primordial follicle development, we did not determine the cellular targets and mechanism of action of the inhibitors.
  
  
  
  These results are the first to implicate the JNK pathway in primordial follicle activation and could have significant consequences for the successful development of fertility preservation strategies and our understanding of primordial follicle activation.
  
  
  
  n/a.
  
  
  
  Dr Michael J. Bertoldo and the laboratories involved in the present study were supported by a grant from 'Région Centre' (CRYOVAIRE, Grant number #320000268). There are no conflicts of interest to declare.
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France School of Women's and Children's Health, Discipline of Obstetrics and Gynaecology, University of New South Wales, Sydney, Australia michael.bertoldo@unsw.edu.au.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bertoldo
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France MNHN, Laboratoire de la Réserve de la Haute Touche, Obterre 36290, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Bernard
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France MNHN, Laboratoire de la Réserve de la Haute Touche, Obterre 36290, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Duffard
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France CNRS, UMR7247, Nouzilly 37380, France Université François Rabelais de Tours, Tours 37041, France IFCE, Nouzilly 37380, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Tsikis
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France CNRS, UMR7247, Nouzilly 37380, France Université François Rabelais de Tours, Tours 37041, France IFCE, Nouzilly 37380, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Alves
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Calais
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France CNRS, UMR7247, Nouzilly 37380, France Université François Rabelais de Tours, Tours 37041, France IFCE, Nouzilly 37380, France.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Uzbekova
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France CNRS, UMR7247, Nouzilly 37380, France Université François Rabelais de Tours, Tours 37041, France IFCE, Nouzilly 37380, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Monniaux
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France CNRS, UMR7247, Nouzilly 37380, France Université François Rabelais de Tours, Tours 37041, France IFCE, Nouzilly 37380, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Mermillod
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France MNHN, Laboratoire de la Réserve de la Haute Touche, Obterre 36290, France CNRS, UMR7247, Nouzilly 37380, France Université François Rabelais de Tours, Tours 37041, France IFCE, Nouzilly 37380, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Locatelli
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D054304:Anti-Mullerian Hormone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000873:Anthracenes; D016755:Proto-Oncogene Proteins c-jun; C432165:pyrazolanthrone; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone
keywords: Foxo3a; anti-Mullerian hormone; c-Jun-N-terminal kinase; fertility preservation; in vitro ovarian tissue culture; primordial follicle activation