Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells.
Mammalian oocytes are deficient in their ability to carry out glycolysis. Therefore, the products of glycolysis that are necessary for oocyte development are provided to oocytes by companion cumulus cells. Mouse oocytes secrete paracrine factors that promote glycolysis in cumulus cells. The objective of this study was to identify paracrine factors secreted by oocytes that promote glycolysis and expression of mRNA encoding the glycolytic enzymes PFKP and LDHA. Candidates included growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and fibroblast growth factors (FGFs). Bmp15-/- and Gdf9+/- Bmp15-/- (double mutant, DM) cumulus cells exhibited reduced levels of both glycolysis and Pfkp and Ldha mRNA, and mutant oocytes were deficient in promoting glycolysis and expression of Pfkp and Ldha mRNA in cumulus cells of wild-type (WT) mice. Alone, neither recombinant BMP15, GDF9 nor FGF8 promoted glycolysis and expression of Pfkp and Ldha mRNA in WT cumulus cells. Co-treatment with BMP15 and FGF8 promoted glycolysis and increased expression of Pfkp and Ldha mRNA in WT cumulus cells to the same levels as WT oocytes; however, the combinations of BMP15/GDF9 or GDF9/FGF8 did not. Furthermore, SU5402, an FGF receptor-dependent protein kinase inhibitor, inhibited Pfkp and Ldha expression in cumulus cells promoted by paracrine oocyte factors. Therefore, oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells.
Sugiura
Koji
K
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Su
You-Qiang
YQ
Diaz
Francisco J
FJ
Pangas
Stephanie A
SA
Sharma
Shweta
S
Wigglesworth
Karen
K
O'Brien
Marilyn J
MJ
Matzuk
Martin M
MM
Shimasaki
Shunichi
S
Eppig
John J
JJ
D000818:Animals; D055430:Bone Morphogenetic Protein 15; D002478:Cells, Cultured; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006019:Glycolysis; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D051379:Mice; D008817:Mice, Mutant Strains; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D025502:Phosphofructokinase-1, Type C / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C496457:Fgf8 protein, mouse; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D011994:Recombinant Proteins; C105686:SU 5402; D051524:Fibroblast Growth Factor 8; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D025502:Phosphofructokinase-1, Type C; C421526:phosphofructokinase-1 subunit, type C