title: Mouse oocyte meiotic resumption and polar body extrusion in vitro are differentially influenced by FSH, epidermal growth factor and meiosis-activating sterol.
abstract: BACKGROUND
  In this study, we compared the relative ability of FSH (100 mIU/ml), epidermal growth factor (EGF) (10 ng/ml), and follicular-fluid meiosis-activating sterol (FF-MAS, 10 micromol/l) to induce meiotic resumption and polar body I (PBI) extrusion in mouse oocytes.
  
  
  METHODS
  Cumulus-enclosed oocytes (CEO) were co-incubated with meiosis-arresting agents, including 4 mmol/l hypoxanthine (Hx), 0.3 mmol/l dibutyryl cAMP (dbcAMP), and 8.5 micromol/l cilostamide, a selective inhibitor of the oocyte-specific phosphodiesterase 3 (PDE 3).
  
  
  RESULTS
  In Hx-treated oocytes, FSH, EGF and FF-MAS induced meiosis resumption at very high rates, but only FSH and EGF also promoted PBI extrusion with high frequency. In experiments conducted in the presence of dbcAMP, FF-MAS was unable to promote an increase in germinal vesicle breakdown (GVBD) rate, whereas FSH and EGF generated a response similar to the Hx groups. Neither FSH, EGF nor FF-MAS caused any change in the meiotic status of CEO when meiotic arrest at the germinal vesicle (GV) stage was maintained by cilostamide. In the presence of Hx, naked oocytes (NkO) co-cultured with their cumulus cells were able to respond to the GVBD-inducing effect of FSH and EGF by resuming meiosis at high rate.
  
  
  CONCLUSIONS
  Collectively, these results indicate that: (i) a signal triggered in cumulus cells by either FSH or EGF, but not necessarily coincident with FF-MAS, may contribute to meiotic maturation, supporting GVBD and extrusion of PBI; (ii) the transmission of this signal can occur in a paracrine fashion, at least with reference to the breakdown of the GV. It also appears that concomitant regulation of intra-oocyte cAMP degradation is a prerequisite for meiosis resumption.
authors.affiliation: TECNOBIOS Procreazione, Bologna, 40125, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Coticchio
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: Borini
authors.forename: C
authors.initials: C
authors.lastname: Grøndahl
authors.forename: G
authors.initials: G
authors.lastname: Macchiarelli
authors.forename: C
authors.initials: C
authors.lastname: Flamigni
authors.forename: S
authors.initials: S
authors.lastname: Fleming
authors.forename: S
authors.initials: S
authors.lastname: Cecconi
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002782:Cholestenes / Q000494:pharmacology*; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D019271:Hypoxanthine / Q000494:pharmacology; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology; D015363:Quinolones / Q000494:pharmacology
chemical_list: D002782:Cholestenes; D015363:Quinolones; D019271:Hypoxanthine; C021294:cilostamide; D004815:Epidermal Growth Factor; D003994:Bucladesine; C100324:4,4-dimethylcholesta-8,14,24-trienol; D005640:Follicle Stimulating Hormone