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A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

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Texas A and M Agrilife Research College Station United States

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Transforming growth factor beta TGFB family members regulate multiple cellular functions and key reproductive processes in a contextually dependent manner via the interaction with membrane associated serinethreonine kinase receptor complexes TGFBR1TGFBR2 and downstream SMAD proteins. To complement our mouse model containing a constitutively active TGFBR1 using growth differentiation factor 9 Gdf9-Cre i.e., TGFBR1-gCA, we herein generated a mouse model using Zp3-Cre line termed TGFBR1-zCA. We performed a number of experiments including H and E staining, immunohistochemistry, and apoptosis assay to analyze potential ovarian phenotype of these mice. In contrast to TGFBR1-gCA mice, the TGFBR1-zCA mice did not develop ovarian tumors and demonstrated essentially normal ovarian histology and expression of granulosa cell and germ cell proteins. Using ovarian RNA from TGFBR1-gCA mice and controls, we performed RNA-seq experiment. Initial analysis identified 1301 genes that were differentially regulated in the TGFBR1-zCA ovaries versus controls. Interestingly, a number of genes are associated with folliculogenesis and oogenesis. Further studies will be focused on exploiting the RNAseq data and defining key regulators andor pathways for ovarian tumor development.

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Technical Report,15 Apr 2016,14 Apr 2017



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Approved For Public Release;

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