A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development
Technical Report,15 Apr 2015,14 Apr 2018
Texas A and M Agrilife Research College Station United States
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Transforming growth factor beta TGFB signaling regulates fundamental reproductive events via TGFB receptor complexes TGFBR1TGFBR2 and downstream SMAD proteins. To determine potential effect of overactivation of TGFB signaling in distinct cellular compartments, we generated a mouse model containing a constitutively active TGFBR1 using growth differentiation factor 9 Gdf9-Cre termed TGFBR1-gCA. We showed that sustained activation of TGFBR1 disrupts folliculogenesis via affecting ovarian reserve and follicle growthdevelopment. Ovarian tumor tissues from TGFBR1-gCA mice were positive for granulosa cell markers. RNA-Seq analysis using ovarian RNA from TGFBR1-gCA mice and controls identified a number of genes associated with folliculogenesis, oogenesis, proliferation, and differentiation. Histological and molecular analyses provided evidence of overactivation of TGFB signaling in ovarian granulosa cell compartment. The mouse model may be further exploited to define the cellular and molecular mechanisms of TGFBactivin downstream signaling in granulosa cell tumor development.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology