Paternal malnutrition programs offspring’s breast cancer risk and tumor metabolism in a mouse model (MBD-seq)

We found that LP daughters have lower birthweight, alterations in mammary gland morphology and higher rates of mammary cancer. Further, we found that mammary glands and tumors of LP daughters are metabolic rewired, with alterations in the AMPK and amino-acid metabolism pathways. These changes were associated with differential expression of miRNAs 451a, miR-200c and miR-92a. Importantly, some of the same miRNAs and target genes alterations were detected in breast tumors of women from populations with high rates of low birthweight. Male mice were fed AIN93G-based diets containing either 17.7% (control) or 8.9% (LP) energy from protein from 3 to 10 weeks of age. Males on either group were mated to females raised on a control diet. Female offspring control and LP fathers were treated with 7,12-dimethylbenz[a]anthracene (DMBA) to initiate mammary carcinogenesis. Mature sperm from fathers and mammary tissue from female offspring were used for DNA methylation analyses.