Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse.
This study investigated the participation of MAPK in the resumption of meiosis [germinal vesicle breakdown (GVB)] in oocytes and cumulus expansion using oocyte-cumulus cell complexes (OCC) from Mos-null mice (Mos(tm1Ev)/Mos(tm1Ev), hereafter Mos(-/-)). MAPK activity was not detected in Mos(-/-) oocytes whether they matured in vivo or in vitro, with or without gonadotropin stimulation. Therefore, there are no pathways independent of MOS that activate MAPK during gonadotropin-induced maturation. In contrast, MAPK activity was always detected coincident with GVB in Mos(+/+) oocytes. Moreover, MAPK activity was detected in cumulus cells before gonadotropin-induced GVB in OCC regardless of genotype. A specific inhibitor (U0126) of MEK, a MAPKK required for MAPK activity, inhibited gonadotropin-induced GVB in OCC of both Mos(+/+) and Mos(-/-) mice. Activation of MAPK was downstream of elevation of cAMP. U0126 also inhibited cumulus expansion stimulated by FSH, epidermal growth factor, 8-bromo-cAMP, and recombinant growth differentiation factor-9. It is concluded that under the in vitro conditions used here, gonadotropin-induced GVB requires the participation of MAPK activity in the cumulus cells, but not in the oocyte. Moreover, the induction of cumulus expansion also requires the participation of MAPK, and this action is downstream of both elevation of cAMP and growth differentiation factor-9.
Su
You-Qiang
YQ
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Wigglesworth
Karen
K
Pendola
Frank L
FL
O'Brien
Marilyn J
MJ
Eppig
John J
JJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D055430:Bone Morphogenetic Protein 15; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006062:Gonadotropins / Q000494:pharmacology*; D055429:Growth Differentiation Factor 9; D006133:Growth Substances / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology* / Q000201:enzymology*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology
C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D002070:Butadienes; D004791:Enzyme Inhibitors; C525898:Gdf9 protein, mouse; D006062:Gonadotropins; D055429:Growth Differentiation Factor 9; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D009570:Nitriles; D011994:Recombinant Proteins; C113580:U 0126; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D005640:Follicle Stimulating Hormone; D020928:Mitogen-Activated Protein Kinases