Inhibition of MTOR signaling impairs rat embryo organogenesis by affecting folate availability
- 1 April 2021
- journal article
- research article
- Published by Bioscientifica in Reproduction
- Vol. 161 (4), 365-373
- https://doi.org/10.1530/rep-20-0603
Abstract
Mechanistic target of rapamycin (mTOR) is essential for embryo development by acting as a nutrient sensor to regulate cell growth, proliferation and metabolism. Folate is required for embryonic ribosomal protein S6, a downstream target of mTOR Complex1, markedly reduced embryonic folate incorporation (-84%, p<0.01) and induced embryo normal embryonic development and it was recently reported that mTOR functions as a folate sensor. In this work we tested the hypothesis that mTOR functions as a folate sensor in the embryo and its inhibition results in embryonic developmental delay affecting neural tube closure and that these effects can be rescued by folate supplementation. Administration of rapamycin (0.5 mg/kg) to rats during early organogenesis inhibited developmental impairments, as shown by an increased resorption rate, reduced embryo somite number and delayed neural tube closure. These alterations were prevented by folic acid administered to the dams. Differently, although an increased rate of embryonic rotation defects were observed in the rapamycin treated dams, this alteration was not prevented by maternal folic acid supplementation. In conclusion, mTOR inhibition during organogenesis in the rat resulted in decreased folate levels in the embryo, increased embryo resorption rate and impaired embryo development. These data suggest that mTOR signaling influences embryo folate availability, possibly by regulating transfer of folate across the maternal-embryonic interface.Keywords
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