(P21-013-25) Variations in Phenotype, Methylation Potential and Gene Expression of Methyltransferases in Wistar Rat Offspring Exposed to Choline or Betaine Prenatally

Objectives: Choline and its oxidized product, betaine, are important nutrients for early development and provide labile methyl groups for methylation reactions. We have shown that a diet devoid of choline with high folic acid consumed during pregnancy leads to higher body weight and lower global DNA methylation in Wistar rat offspring. Here, we determined the role of prenatal supplies of choline or betaine as determinants of body weight, methylation potential, and gene expression of methyltransferases in offspring.

Methods: Pregnant dams were provided an AIN-93G diet and drinking water with either 0.25% w/w choline as choline bitartrate (CB), 0.25% betaine anhydrous (BA), or no treatment (control). All offspring were weaned to a high-fat diet for 12 weeks. Body weight, hepatic concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and gene expression of methyltransferases were measured.

Results: Female offspring of CB and BA dams (p < 0.05) and male offspring of BA dams (p < 0.05) had lower body weight compared to untreated control, with male offspring of CB dams not different from untreated control and BA. Female offspring of CB dams had higher SAM:SAH (a marker of methylation potential) compared to untreated control, with BA not different from untreated control and CB (p < 0.05). Gene expression of DNA methyltransferase (DNMT) 1 and phosphatidylethanolamine N-methyltransferase (PEMT) in female offspring of BA dams were higher than untreated control with CB not different from untreated control and BA (p < 0.05). Male offspring of BA dams had the highest SAM:SAH followed by CB compared to untreated control (p < 0.001), consistent with stepwise elevations in DNMT1 expression (p < 0.0001). Male offspring of CB and BA groups had higher expression of DNMT3A (p < 0.0001) and DNMT3B (p < 0.01) with alterations in glycine N-methyltransferase (p < 0.001) and PEMT (p < 0.01).

Conclusions: Choline and betaine are metabolically related but their impact on methylation potential varied through the regulation of different methyltransferases in a sex-dependent manner. Our results are significant in illuminating epigenetic patterns that may be specified with dietary components in shaping long-term health trajectory.

Funding Sources: NSERC-DG; UofG Team Building Grant; CIHR CGS-M to GVS; URA to EMP; CIHR CRC II to CEC