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dc.contributor.authorBennett, Jill
dc.contributor.authorBaumgarten, Sarah C.
dc.contributor.authorStocco, Carlos
dc.date.accessioned2014-02-19T05:14:29Z
dc.date.available2014-12-23T10:30:12Z
dc.date.issued2013-12
dc.identifier.bibliographicCitationBennett J, Baumgarten SC, Stocco C. GATA4 and GATA6 silencing in ovarian granulosa cells affects levels of mRNAs involved in steroidogenesis, extracellular structure organization, IGF-I activity, and apoptosis. Endocrinology. 2013 Dec;154(12):4845-58. doi: 10.1210/en.2013-1410.en_US
dc.identifier.issn1945-7170
dc.identifier.urihttp://hdl.handle.net/10027/11175
dc.descriptionThis is a copy of an article published in the Endocrinology © 2013 Endocrine Societyen_US
dc.description.abstractKnockdown of the transcription factors GATA4 and GATA6 in granulosa cells (GCs) impairs folliculogenesis and induces infertility. To investigate the pathways and genes regulated by these factors, we performed microarray analyses on wild-type GCs or GCs lacking GATA4, GATA6, or GATA4/6 (G4(gcko), G6(gcko), and G4/6(gcko)) after in vivo treatment with equine chorionic gonadotropin. GATA4 deletion affected a greater number of genes than GATA6, which correlates with the subfertility observed in G4(gcko) mice and the normal reproductive function found in G6(gcko) animals. An even greater number of genes were affected by the deletion of both factors. Moreover, the expression of FSH receptor, LH receptor, inhibin α and β, versican, pregnancy-associated plasma protein A, and the regulatory unit 2b of protein kinase A, which are known to be crucial for ovarian function, was greatly affected in double GATA4 and GATA6 knockouts when compared with single GATA-deficient animals. This suggests that GATA4 and GATA6 functionally compensate for each other in the regulation of key ovarian genes. Functional enrichment revealed that ovulation, growth, intracellular signaling, extracellular structure organization, gonadotropin and growth factor actions, and steroidogenesis were significantly regulated in G4/6(gcko) mice. The results of this analysis were confirmed using quantitative polymerase chain reaction, immunohistochemical, and biological assays. Treatment of GCs with cAMP/IGF-I, to bypass FSH and IGF-I signaling defects, revealed that most of the affected genes are direct targets of GATA4/6. The diversity of pathways affected by the knockdown of GATA underscores the important role of these factors in the regulation of GC function.en_US
dc.description.sponsorshipThis work was supported by National Institutes of Health Grants R01HD057110 and R21HD066233.en_US
dc.language.isoen_USen_US
dc.publisherEndocrine Societyen_US
dc.subjectapoptosisen_US
dc.subjectgranulosa cellen_US
dc.subjectcell differentiationen_US
dc.titleGATA4 and GATA6 Silencing in Ovarian Granulosa Cells Affects Levels of mRNAs Involved in Steroidogenesis, Extracellular Structure Organization, IGF-I Activity, and Apoptosisen_US
dc.typeArticleen_US


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