Effect of maternal methyl diet on epigenetic changes and mammary carcinogenesis in offspring
Abstract
Maternal nutrition influences the offspring's growth and metabolism while also affecting the susceptibility to diet‐related diseases such as cancer in adulthood. Lipotropes (choline, methionine, folic acid, and vitamin B12) play a role in DNA methylation, an epigenetic mechanism controlling the expression of genes involved in cell growth and metabolism. We studied the effects of a maternal lipotrope‐additive diet (LAD) on epigenetic changes and mammary cancer risk in female rat offspring. Dams were fed either a control diet (CD) or LAD during gestation and lactation. Their female offspring were weaned onto the CD and used for: 1) analysis of DNA methylation and gene expression in mammary tissues, and 2) a mammary carcinogenesis experiment using nitrosomethylurea. We observed a significant increase of 22% in global DNA methylation and a tendency toward decreased mRNA expression of the DNA methyltransferase1 gene in the LAD group. The offspring of the LAD‐fed dams also showed an increased latency period of 17%, along with decreased tumor incidence (27%), tumor numbers (57%), and tumor volume (33%). Our study suggests in utero and early postnatal exposure to LAD increases global DNA methylation in mammary glands, while also reducing mammary tumorigenesis. Future studies will be required to establish the detailed mechanisms responsible. Supported in part by a US Department of Defense grant.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2012
- Source ID
- 10.1096/fasebj.26.1_supplement.1023.10
Entities
People
- Chung S. Park
- Kyongshin Cho
- Lawrence Mabasa
- Mark William Walters
- Sajin Bae
Organizations
- North Dakota State University
- United States Department of Defense