Folic acid intake during juvenile/peri-pubertal development modulates the mammary tissue transcriptome of female C56BL/6 mice

We tested the hypothesis that high FA (HFA) intake alters the juvenile/peri-pubertal mammary transcriptome in a manner consistent with increased potential for breast cancer, detectable beyond the period of intake. C57BL/6 mice were fed control FA (CFA) (1 mg/kg diet) or HFA (5 mg/kg diet) diets for 4 weeks, followed by AIN93M maintenance diet for 4 weeks. RNA sequencing of the mammary transcriptome (~83 million reads) showed 18 transcripts (17 downregulated) differentially expressed between groups. Gene Set Enrichment showed downregulated genes significantly enriched in oxidative phosphorylation, adipogenesis, fatty acid metabolism and epithelial mesenchymal transition. Cancer and developmental disorder were the most altered Disease and Disorder pathways, with top upstream regulators identified as DNA methyltransferases. This study demonstrates HFA intake during juvenile/peri-pubertal mammary development induces changes in the mammary transcriptome associated with altered energy metabolism, cell neoplasia and epigenetic regulation of gene.