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Oocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of mouse cumulus cell expansion

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dc.contributor.authorDragovic, R.
dc.contributor.authorRitter, L.
dc.contributor.authorSchulz, S.
dc.contributor.authorAmato, F.
dc.contributor.authorThompson, J.
dc.contributor.authorArmstrong, D.
dc.contributor.authorGilchrist, R.
dc.date.issued2007
dc.description© 2007 by the Society for the Study of Reproduction, Inc.
dc.description.abstractExpansion of the mouse cumulus-oocyte complex (COC) is dependent on oocyte-secreted paracrine factors. Transforming growth factor beta (TGFB) superfamily molecules are prime candidates for the cumulus expansion-enabling factors (CEEFs), and we have recently determined that growth differentiation factor 9 (GDF9) alone is not the CEEF. The aim of this study was to examine oocyte paracrine factors and their signaling pathways that regulate mouse cumulus expansion. Using RT-PCR, oocytes were found to express the two activin subunits, Inhba and Inhbb, and activin A and activin B both enabled FSH-induced cumulus expansion of oocytectomized (OOX) complexes. Follistatin, an activin-binding protein, neutralized activin-induced expansion but had no effect on oocyte-induced expansion. The type I receptors for GDF9 and activin are activin receptor-like kinase 5 (ALK5) and ALK4, respectively, both of which activate the same SMAD 2/3 signaling pathway. We examined the requirement for this signaling system using an ALK 4/5/7 inhibitor, SB-431542. SB-431542 completely ablated FSH-stimulated GDF9-, activin A-, activin B-, and oocyte-induced cumulus expansion. Moreover, SB-431542 also antagonized epidermal growth factor-stimulated, oocyte-induced cumulus expansion. Using real-time RT-PCR, SB-431542 also attenuated GDF9-, activin A-, and oocyte-induced OOX expression of hyaluronan synthase 2, tumor necrosis factor alpha-induced protein 6, prostaglandin synthase 2, and pentraxin 3. This study provides evidence that the CEEF is composed of TGFB superfamily molecules that signal through SMAD 2/3 to enable the initiation of mouse cumulus expansion.
dc.description.statementofresponsibilityRebecca A. Dragovic, Lesley J. Ritter, Samantha J. Schulz, Fred Amato, Jeremy G. Thompson, David T. Armstrong, and Robert B. Gilchrist
dc.identifier.citationBiology of Reproduction, 2007; 76(5):848-857
dc.identifier.doi10.1095/biolreprod.106.057471
dc.identifier.issn0006-3363
dc.identifier.issn1529-7268
dc.identifier.orcidRitter, L. [0000-0001-5942-851X]
dc.identifier.orcidThompson, J. [0000-0003-4941-7731]
dc.identifier.orcidGilchrist, R. [0000-0003-1611-7142]
dc.identifier.urihttp://hdl.handle.net/2440/43460
dc.language.isoen
dc.provenanceBOR - Papers in Press, published online ahead of print December 27, 2006.
dc.publisherSoc Study Reproduction
dc.source.urihttps://doi.org/10.1095/biolreprod.106.057471
dc.subjectactivin
dc.subjectcumulus cells
dc.subjectgrowth factors
dc.subjectoocyte development
dc.subjectsignal transduction
dc.titleOocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of mouse cumulus cell expansion
dc.typeJournal article
pubs.publication-statusPublished

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