title: Evaluation of members of the TGFbeta superfamily as candidates for the oocyte factors that control mouse cumulus expansion and steroidogenesis.
abstract: Oocytes secrete factors that control cumulus and granulosa functions, including cumulus expansion and steroid hormone production. Some members of the transforming growth factor beta (TGFbeta) superfamily influence these activities, yet it is still not determined conclusively whether any of these superfamily members are the previously reported oocyte-secreted factors. The aim of this study was to examine the effects of TGFbeta1 and growth differentiation factor 9 (GDF-9) on cumulus expansion and progesterone production by mouse oocytectomized (OOX) complexes in culture. TGFbeta1 mimics the effects of oocytes by both enabling cumulus expansion and inhibiting progesterone production; however, neutralizing antibodies to TGFbeta1 in cultures of cumulus-oocyte complexes (COCs) or in co-cultures of OOX complexes failed to inhibit the ability of oocytes to enable cumulus expansion or inhibit progesterone production. Activin A had no effect on progesterone production by OOX complexes. In experiments using oocytes obtained from mice with deficient expression of GDF-9, OOX complexes cultured in the presence of heterozygous oocytes were capable of full expansion, whereas OOX complexes cultured with oocytes from GDF-9 null mice did not expand. Similarly, GDF-9 null oocytes failed to suppress FSH-induced progesterone production by OOX complexes. These results support the hypothesis that GDF-9 is the cumulus expansion enabling factor produced by mouse oocytes and that GDF-9 also inhibits cumulus progesterone production; however, the possibility remains that loss of GDF-9 may indirectly affect the ability of oocytes to produce the factors that regulate cumulus cell activity.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa Regional Cancer Centre, 503 Smyth Road, Ottawa, Canada K1H 1C4. Barbara.Vanderhyden@orcc.on.ca
authors.forename: B C
authors.initials: BC
authors.lastname: Vanderhyden
authors.forename: E A
authors.initials: EA
authors.lastname: Macdonald
authors.forename: E
authors.initials: E
authors.lastname: Nagyova
authors.forename: A
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D055430:Bone Morphogenetic Protein 15; D018920:Coculture Techniques; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000378:metabolism; D055429:Growth Differentiation Factor 9; D028322:Inhibin-beta Subunits / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009865:Oocytes / Q000502:physiology*; D011374:Progesterone / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*; D015044:Zona Pellucida / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits