title: A synthetic analogue of meiosis-activating sterol (FF-MAS) is a potent agonist promoting meiotic maturation and preimplantation development of mouse oocytes maturing in vitro.
abstract: BACKGROUND
  Follicular fluid-meiosis-activating sterol (FF-MAS) is a factor present in the pre-ovulatory follicle during the time of oocyte maturation. In mouse oocytes maturing in vitro, FF-MAS promotes the completion of meiotic maturation to metaphase II (MII) and improves competence to complete the 2-cell stage to blastocyst transition. We produced analogues of FF-MAS and selected three on the basis of potency to promote the resumption of meiosis by mouse oocytes maintained in meiotic arrest by hypoxanthine. The objective of this study was to determine whether these FF-MAS analogues also affect the quality of oocytes maturing in vitro with respect to the completion of meiotic maturation and augmenting the frequency of development to the blastocyst stage after fertilization in vitro.
  
  
  METHODS
  Cumulus cell-enclosed oocytes were isolated from the small antral follicles of 18 or 20 day post-natal mice. These oocytes normally have a reduced competence to complete meiotic maturation and preimplantation embryo development. Oocytes were isolated at the germinal vesicle stage and matured in vitro using media supplemented with 0.1% ethanol, 1 micromol/l FF-MAS, or 0.1-10 micromol/l FF-MAS analogues ZK255884 (884), ZK255933 (933) and ZK255991 (991). Oocytes that progressed to MII were fertilized in vitro and the percentage developing to the 2-cell and blastocyst stages was determined.
  
  
  RESULTS
  At 1 micromol/l, 991 and 933 increased the portion of oocytes progressing to MII, whereas the lowest dose of 991 and 884 was ineffective. Treatment of maturing oocytes with either 0.1 or 1 micromol/l 933 dramatically increased oocyte competence to complete preimplantation development.
  
  
  CONCLUSIONS
  The synthetic analogue of FF-MAS, ZK255933, is a potent agonist that improves the quality of mouse oocytes matured in vitro. This compound may therefore have therapeutic value for treatment of oocytes from women undergoing therapy for infertility owing to poor oocyte quality.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Marín Bivens
authors.forename: B
authors.initials: B
authors.lastname: Lindenthal
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Brien
authors.forename: K
authors.initials: K
authors.lastname: Wigglesworth
authors.forename: T
authors.initials: T
authors.lastname: Blume
authors.forename: C
authors.initials: C
authors.lastname: Grøndahl
authors.forename: J J
authors.initials: JJ
authors.lastname: Eppig
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D002478:Cells, Cultured; D002782:Cholestenes / Q000138:chemical synthesis / Q000494:pharmacology*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D009866:Oogenesis / Q000187:drug effects*
chemical_list: D002782:Cholestenes; C496998:ZK255933; C100324:4,4-dimethylcholesta-8,14,24-trienol