Dietary zinc deficiency or supplementation during gestation increases breast cancer susceptibility in adult female mice offspring following a J-shaped pattern and through distinct mechanisms

Author(s)

da Cruz, Raquel Santana ^[1] ; Andrade, Fabia de Oliveira ^[1] ; de Oca Carioni, Vivian Montes ^[2] ; Rosim, Mariana Papaleo ^[1] ; Paulino Miranda, Mayara Lilian ^[1] ; Fontelles, Camile Castilho ^[1] ; de Oliveira, Pedro Vitoriano ^[2] ; Barbisan, Luis Fernando ^[3] ; Castro, Inar Alves ^[1] ; Ong, Thomas Prates ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Food Sci & Nutr, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Fundamental Chem, BR-05508000 Sao Paulo, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Inst Biosci Botucatu, Dept Morphol, BR-18618970 Sao Paulo, SP - Brazil

^[4] Food Res Ctr FoRC, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Food and Chemical Toxicology; v. 134, DEC 2019.
• Web of Science Citations: 2

Abstract

Zinc is required for fetal development and is involved in key processes associated with breast carcinogenesis. We evaluated whether maternal zinc deficiency or supplementation during gestation influences female offspring susceptibility to breast cancer in adulthood. C57BL/6 mice consumed during gestation control (30 p.p.m. zinc), zinc-deficient (8 p.p.m) or zinc-supplemented (45 p.p.m.) diets. Maternal zinc supplementation increased in female mice offspring the incidence of chemically-induced mammary adenocarcinomas that were heavier, compared to control group. This was accompanied by a decreased number of terminal end buds, increased cell proliferation and apoptosis, and increased tumor suppressors p21, p53 and Rassfl, Zfp382 and Stat3 expression in mammary glands, as well as increased zinc status. Although maternal zinc deficiency did not alter the incidence of these lesions, it also induced heavier Mammary adenocarcinomas, compared to control group. These effects were accompanied by a decreased number of terminal end buds, increased proto-oncogenes c-Myc and Lmo4 expression and H3K9Me3 and H4K2OMe3 epigenetic marks in mammary glands of offspring, and decreased zinc status and increased levels of oxidative marker malondialdehyde. The data suggest that both maternal zinc deficiency and supplementation during gestation programmed increased breast cancer susceptibility in adult mice offspring following a J-shaped pattern through distinct mechanisms. (AU)

• FAPESP's process: 13/04960-9 - Nutrition and fetal origin of breast cancer: effect of zinc deficiency or supplementation during gestational phase of mice on offspring's susceptibility to mammary carcinogenesis
• Grantee: Raquel Santana da Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/07914-8 - FoRC - Food Research Center
• Grantee: Bernadette Dora Gombossy de Melo Franco
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/23259-4 - Maternal nutrition and breast cancer fetal programming: influence of nutrient-epigenome interactions in early life
• Grantee: Thomas Prates Ong
• Support Opportunities: Regular Research Grants