title: The Adequate Corpus Luteum: miR-96 Promotes Luteal Cell Survival and Progesterone Production.
abstract: Inadequate progesterone production from the corpus luteum is associated with pregnancy loss. Data available in model species suggest important roles of microRNAs (miRNAs) in luteal development and maintenance.
  
  
  
  To comprehensively investigate the involvement of miRNAs during the ovarian follicle-luteal transition.
  
  
  
  The effects of specific miRNAs on survival and steroid production by human luteinized granulosa cells (hLGCs) were tested using specific miRNA inhibitors. Candidate miRNAs were identified through microarray analyses of follicular and luteal tissues in a bovine model.
  
  
  
  An academic institution in the United Kingdom associated with a teaching hospital. hLGCs were obtained by standard transvaginal follicular-fluid aspiration from 35 women undergoing assisted conception.
  
  
  
  Inhibition of candidate miRNAs in vitro.
  
  
  
  Levels of miRNAs, mRNAs, FOXO1 protein, apoptosis, and steroids were measured in tissues and/or cultured cells.
  
  
  
  Two specific miRNA clusters, miR-183-96-182 and miR-212-132, were dramatically increased in luteal relative to follicular tissues. miR-96 and miR-132 were the most upregulated miRNAs within each cluster. Database analyses identified FOXO1 as a putative target of both these miRNAs. In cultured hLGCs, inhibition of miR-96 increased apoptosis and FOXO1 protein levels, and decreased progesterone production. These effects were prevented by small interfering RNA-mediated downregulation of FOXO1. In bovine luteal cells, miR-96 inhibition also led to increases in apoptosis and FOXO1 protein levels.
  
  
  
  miR-96 targets FOXO1 to regulate luteal development through effects on cell survival and steroid production. The miR-183-96-182 cluster could provide a novel target for the manipulation of luteal function.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
authors.forename: Bushra T
authors.initials: BT
authors.lastname: Mohammed
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
authors.forename: Sadanand D
authors.initials: SD
authors.lastname: Sontakke
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
authors.forename: Jason
authors.initials: J
authors.lastname: Ioannidis
authors.affiliation: The Queen's Medical Research Institute, MRC Centre for Reproductive Health, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Donadeu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002417:Cattle; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008184:Luteal Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D013045:Species Specificity; D015854:Up-Regulation / Q000235:genetics
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D011374:Progesterone