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

Koji Sugiura, You Qiang Su, Francisco J. Diaz, Stephanie A. Pangas, Shweta Sharma, Karen Wigglesworth, Marilyn J. O'Brien, Martin M. Matzuk, Shunichi Shimasaki, John J. Eppig

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

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 G6DF9/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.

Original languageEnglish (US)
Pages (from-to)2593-2603
Number of pages11
JournalDevelopment
Volume134
Issue number14
DOIs
StatePublished - Jul 2007

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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