Oocyte-dependent activation of mitogen-activated protein kinase (ERK1/2) in cumulus cells is required for the maturation of the mouse oocyte-cumulus cell complex.
Luteinizing hormone (LH) induces maturational processes in oocyte-cumulus cell complexes (OCC) of preovulatory follicles that include both resumption of meiosis in the oocyte and expansion (mucification) of the cumulus oophorus. Both processes require activation of mitogen-activated protein kinase (MAPK) in granulosa cells. Here, it is reported that inhibition of MAPK activation prevented gonadotropin-stimulated resumption of meiosis as well as the rise in expression of two genes whose products are necessary for normal cumulus expansion, Has2 and Ptgs2. However, inhibition of MAPK did not block gonadotropin-induced elevation of granulosa cell cAMP, indicating that the activation of MAPK required for inducing GVB and cumulus expansion is downstream of cAMP. Moreover, activation of MAPK in cumulus cells requires one or more paracrine factors from the oocyte to induce GVB and cumulus expansion; MAPK activation alone is not sufficient to initiate these maturational processes. This study demonstrates a remarkable interaction between the oocyte and cumulus cells that is essential for gonadotropin-induced maturational processes in OCC. By enabling gonadotropin-dependent MAPK activation in granulosa cells, oocytes promote the generation of a return signal from these cells that induces the resumption of meiosis. It also appears that an oocyte-dependent pathway downstream from oocyte-enabled activation of MAPK, and distinct from that promoting the resumption of meiosis, governs cumulus expansion.
Su
You-Qiang
YQ
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Denegre
James M
JM
Wigglesworth
Karen
K
Pendola
Frank L
FL
O'Brien
Marilyn J
MJ
Eppig
John J
JJ
D000818:Animals; D055430:Bone Morphogenetic Protein 15; D002070:Butadienes / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004789:Enzyme Activation; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000235:genetics; D055429:Growth Differentiation Factor 9; D000076002:Hyaluronan Synthases; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology* / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics
C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D002070:Butadienes; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009570:Nitriles; C113580:U 0126; D005640:Follicle Stimulating Hormone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; D000076002:Hyaluronan Synthases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases