Analysis of morphological and epigenetic parameters in the mammary gland of female offspring of rats exposed to selenium deficiency or supplementation during gestation

• Grant number: 14/18500-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): January 01, 2015
• Effective date (End): October 31, 2015
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Thomas Prates Ong
• Grantee: Mariana Papaléo Rosim
• Supervisor: Leena Hilakivi-Clarke
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Georgetown University, United States
• Associated to the scholarship: 11/16368-1 - Maternal nutrition and fetal programming of breast cancer: influence of selenium deficiency or supplementation during rat gestational period on the susceptibility of female offspring to mammary carcinogenesis, BP.DD

Abstract

Breast cancer is a significant public health problem, representing a major cause of death in women both in the USA and in Brazil. Dietary factors have been identified as important modulators of the risk of developing cancer. Based on epidemiological studies and animal models, the essential micronutrient selenium has been highlighted as a promising dietary factor associated to breast cancer risk reduction. Breast cancer may have its origin in early development and thus the maternal diet could have important implications in the fetal programming of the disease by altering the development of terminal end buds that represent mammary tissue targets of carcinogen initiation. In addition, deregulation of epigenetic processes in the early stages of life by dietary factors could induce permanent changes in the expression patterns of genes involved in cell proliferation, survival and differentiation control that are related to the development of cancer. Selenium was shown to modulate altered epigenetic processes in cancer, including DNA methylation and post-translational modifications in histones. In order to ascertain whether differences in selenium concentration in maternal diet could modulate the susceptibility of female offspring to breast cancer, a biological assay was conducted, in which female rats were fed a diet with 0.15 (CO), 1.0 (SUP) or 0.05 (DEF) ppm of selenium during gestational period and the female offspring subjected to a mammary carcinogenesis model induced by the carcinogen DMBA (Bolsa DD, Proc. FAPESP 2011/16368-1). SUP group presented decreased susceptibility to mammary carcinogenesis, while the DEF group had a greater susceptibility. Since diets with different selenium concentrations during gestation were responsible for modulating breast cancer risk in the female offspring, it is important to analyze the cellular and molecular/epigenetic mechanisms involved in this programming effect. Thus, the aim of the present BEPE project is to evaluate the mammary gland morphology and molecular aspects including epigenetic parameters in the female offspring of rats exposed to selenium deficiency or supplementation during gestation. (AU)