Title : Impact of maternal methyl donor nutrients on TBX2 and TBX3 expression in offspring mammary tumors
Abstract:
Background:
Breast cancer is the most commonly diagnosed cancer in women worldwide, imposing a significant financial burden on healthcare systems and individuals due to high treatment costs and lost productivity. While advances in early detection and treatment have improved survival rates, prevention remains the most effective long-term strategy. Emerging evidence suggests that the maternal environment during pregnancy plays a crucial role in shaping a child's health and disease susceptibility, in part, via epigenetic modifications such as DNA methylation. Notably, maternal dietary lipotropes, including methionine, folic acid, choline, and vitamin B12, have been shown to reduce offspring breast cancer risk in animal models, although the underlying mechanisms remain unclear.
Objective:
This study aimed to identify differentially expressed mammary developmental genes in tumor tissues of offspring exposed to maternal lipotropic nutrients during pregnancy and lactation.
Methods:
Pregnant Sprague-Dawley rats were fed either a control or lipotrope-supplemented diet during pregnancy and lactation. Female offspring were weaned onto a control diet and later exposed to 7,12-Dimethylbenzanthracene (DMBA) to induce mammary tumors. Tumors and normal mammary tissues were collected and analyzed for mRNA expression of key mammary developmental genes, including Tbx2, Tbx3, Wnt10b, Hdac1, and Esr1, using quantitative real-time PCR. Statistical analyses were conducted using GraphPad Prism.
Results:
DMBA-induced tumors were characterized as ductal carcinoma in situ. Gene expression analysis revealed significant upregulation of Tbx2, Tbx3, Hdac1, and Esr1 in tumor tissues compared to normal tissues, while Wnt10b showed no change. Maternal lipotrope supplementation lowered the expression of these genes in tumors, to levels observed in normal mammary tissues. Notably, a positive correlation between Esr1 and Tbx2 was found in tumors of offspring not exposed to lipotropes, but this correlation weakened in offspring exposed to maternal lipotropes.
Conclusion:
These findings suggest that maternal dietary lipotropes may reduce breast cancer risk in offspring by modulating the expression of mammary developmental genes such as Tbx2 and Tbx3. Further studies are needed to investigate the role of DNA methylation in this protective effect.
