Interrelationship between PPARgamma and mTOR pathways in rat decidua during early organogenesis

ROBERTI S, HIGA R, WHITE V, CAPOBIANCO E, JAWERBAUM A

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC

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