Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells

Journal:Development

Place of Publication:UK

Key Words:BMP15, FGF8, Cumulus cells, Glycolysis, Mouse, Oocytes

Abstract: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.

All the Authors:You-Qiang Su, Francisco J Diaz, Stephanie A Pangas, Shweta Sharma, Karen Wigglesworth, Marilyn J O'Brien, Martin M Matzuk, Shunichi Shimasaki

First Author:Koji Sugiura

Indexed by:RESEARCH ARTICLE

Correspondence Author:John J Eppig

Document Code:10.1242/dev.006882

Volume:134

Issue:14

Page Number:2593-2603

ISSN No.:0950-1991

Translation or Not:no

Date of Publication:2007-07-15

Date of Publication:2007-07-15