Methionine-Mediated Protection of Fetal Programming Induced by Synthetic Glucocorticoid Treatment
Year: 2018
Type: dissertation
Abstract: S-adenosylmethionine (SAM) is a modified amino acid that is produced by the methionine cycle and used during DNA methylation. We investigated the methionine cycle as a mechanism through which prenatal synthetic glucocorticoid (sGC) treatment affects DNA methylation and gene expression in the fetus, and whether maternal supplementation with methionine (SAM precursor) could protect against sGC effects. Results indicate that sGC treatment was associated with increased methionine cycle metabolite levels (male plasma SAM and trend for hippocampal SAM-SAH ratio in females) and increased placental gene expression of methyl-donor transporters (Lat2, Rfc). Maternal methionine supplementation led to upregulation of key methylation-related enzymes (Mat2a, Dnmt3a, Dnmt3b) in the female and male hippocampus, though DNA methylation was unaffected. These findings suggest a potential rebound phenomenon in sGC-treated fetuses, and that maternal methionine supplementation can promote DNA methylation in offspring. Future research will further investigate the effects of sGCs and methionine on region-specific DNA methylation.
Source: TSpace (University of Toronto)
Author: Alexandros Mouratidis
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3160140718