CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
mTOR pathways in rat decidua during early organogenesis
Autor/es:
SABRINA LORENA ROBERTI, ROMINA HIGA, VERÓNICA WHITE, EVANGELINA CAPOBIANCO, ALICIA JAWERBAUM.
Lugar:
MAR DEL PLATA
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016
Institución organizadora:
SAIC
Resumen:
Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand activated transcription factor that regulates metabolic processes and has an essential role in embryonic and placental development. Mammalian target of rapamycine (mTOR) signaling is also essential for embryo growth and regulates nutrient transfer through the placenta. The decidua serves for the embryonic histotrophic nutrition before the establishment of a mature placenta. We hypothesized that these two signaling pathways are interrelated in the rat decidua during early organogenesis and thus studied the effect of in vivo inhibition of mTOR and PPARgamma in the decidua during early organogenesis. Methods: Wistar rats were mated and during days 7, 8 and 9 of pregnancy the females received sc injections of rapamycin (mTOR inhibitor), T0070907 (PPARgamma inhibitor) or vehicle. On day 9 of pregnancy, the decidua was explanted and the levels of PPARgamma, phosphorylated and total ribosomal protein S6 (RPS6, phosphorylated through the mTORC1 pathway) and phosphorylated and total serum and glucocorticoid-inducible kinase 1 (SGK1, phosphorylated through the mTORC2 pathway) were evaluated by Western blot. Results: Maternal administration of rapamycin (0.75 mg/kg sc) inhibited 68% of RPS6 phosphorylation. In turn, this inhibition increased PPARgamma levels (36%, p< 0.01). On the other hand, administration of the PPARgamma inhibitor T0070907 (0.001 mg/ kg sc) inhibited mTOR signaling, as shown by the reduced levels of phosphorylated RPS6 (25%, p<0.05) and SGK1 (51%, p<0.01) and no changes in the levels of total RPS6 and SGK1. Conclusions: There is a positive regulation of PPARgamma levels when mTOR is inhibited, and a negative regulation of mTOR signaling when PPARgamma is inhibited, interrelationships that may be relevant in the regulation of nutrients availability during early organogenesis.