mTOR signaling inhibition during organogenesis in the rat increases resorption rate and impairs embryo development by affecting folate availability

THERESA POWELL; ROMINA HIGA; THOMAS JANSSON; FREDRICK ROSARIO; ALICIA JAWERBAUM; THERESA POWELL; ROMINA HIGA; THOMAS JANSSON; FREDRICK ROSARIO; ALICIA JAWERBAUM

Congreso; International Federation of Placenta Associations; 2019

International Federation of Placenta Associations

Background Appropriate folate levels are critical for normal embryo development and growth. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions as a master regulator of protein translation, controlling cell growth, proliferation and metabolism. We recently reported that mTOR signaling functions as a folate sensor in placental trophoblast, thereby identifying a novel mechanism linking folate availability to cell growth and function. We tested the hypothesis that mTOR inhibition results in embryonic developmental delay affecting neural tube closure and that these effects can be rescued by folate supplementation. Methods The mTOR inhibitor, Rapamycin (0.5mg/kg) and/or folic acid (15mg/kg) and/or vehicle were subcutaneously administered to pregnant rats from day 8.5 to 10.5 of pregnancy (n=7 in each group). Embryos were collected at day 10.5 of pregnancy, morphology was recorded, folate levels were determined using a microbiological assay kit and mTOR signaling was determined using western blot analysis of total and phosphorylated S6 and 4E-BP1. Data was analyzed by Chi-square or 2-way-ANOVA. ResultsInhibition of mTOR signaling with rapamycin during organogenesis induced an increase in resorption rates (p