title: Regulation of spontaneous and induced resumption of meiosis in mouse oocytes by different intracellular pathways.
abstract: The mitogen-activated protein kinase-dependent and the cAMP-protein kinase A-dependent signal transduction pathways were studied in cultured mouse oocytes during induced and spontaneous meiotic maturation. The role of the mitogen-activated protein kinase pathway was assessed using PD98059, which specifically inhibits mitogen-activated protein kinase 1 and 2 (that is, MEK1 and MEK2), which activates mitogen-activated protein kinase. The cAMP-dependent protein kinase was studied by treating oocytes with the protein kinase A inhibitor rp-cAMP. Inhibition of the mitogen-activated protein kinase pathway by PD98059 (25 micromol l(-1)) selectively inhibited the stimulatory effect on meiotic maturation by FSH and meiosis-activating sterol (that is, 4,4-dimethyl-5alpha-cholest-8,14, 24-triene-3beta-ol) in the presence of 4 mmol hypoxanthine l(-1), whereas spontaneous maturation in the absence of hypoxanthine was unaffected. This finding indicates that different signal transduction mechanisms are involved in induced and spontaneous maturation. The protein kinase A inhibitor rp-cAMP induced meiotic maturation in the presence of 4 mmol hypoxanthine l(-1), an effect that was additive to the maturation-promoting effect of FSH and meiosis-activating sterol, indicating that induced maturation also uses the cAMP-protein kinase A-dependent signal transduction pathway. In conclusion, induced and spontaneous maturation of mouse oocytes appear to use different signal transduction pathways.
authors.affiliation: Laboratory of Reproductive Biology, Juliane Marie Center for Children, Women and Reproduction, Section 5712, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Leonardsen
authors.forename: A
authors.initials: A
authors.lastname: Wiersma
authors.forename: M
authors.initials: M
authors.lastname: Baltsen
authors.forename: A G
authors.initials: AG
authors.lastname: Byskov
authors.forename: C Y
authors.initials: CY
authors.lastname: Andersen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D002775:Cholestadienols / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D019271:Hypoxanthine / Q000494:pharmacology; D016018:Least-Squares Analysis; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D002775:Cholestadienols; D004791:Enzyme Inhibitors; D005419:Flavonoids; D013873:Thionucleotides; C071868:4,4-dimethylcholesta-8,14-dien-3-ol; C016957:adenosine-3',5'-cyclic phosphorothioate; D019271:Hypoxanthine; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one