Influence of paternal consumption of a high-fat/high-sugar diet and/or orange juice during preconception on C57BL/6 female mice offspring breast cancer risk

Abstract

SILVA, L. B. A. R. Influence of paternal consumption of a high-fat/high-sugar diet and/or orange juice during preconception on C57BL/6 female mice offspring breast cancer risk. 2019. 90 p. Thesis (PhD)-Faculty of Pharmaceutical Sciences, University of São Paulo. Breast cancer is the most frequent cancer in women worldwide. Paternal consumption of a highfat diet has been shown to program breast cancer risk in female offspring. Orange juice is widely consumed and is known for its content of bioactive compounds that may have a role in regulating epigenetic processes. Therefore, the aim of the present study was to evaluate the effects of paternal obesity and orange juice consumption on female offspring susceptibility to chemically-induced breast carcinogenesis. Three-week-old C57BL/6 male mice were distributed in control (CO), control-orange juice (CJ), obese (OB) and obese-orange juice (OJ) groups, fed either a standard chow or a high-fat/high-sugar diet (45% lard-based diet supplemented with sweetened condensed milk), with water or orange juice, for 11 weeks before mating. Female offspring were weaned onto standard chow until 7 weeks of age and then were initiated with 7,12-dimethyl-benzo[a]anthracene to induce mammary tumors. CJ female offspring presented higher multiplicity of mammary tumors (p£0.05) compared to CO offspring. Female offspring from OB group showed higher tumor latency (p£0.05), lower tumor incidence (p£0.05), higher multiplicity of tumors (p£0.05), lower cell proliferation (Ki67) in the mammary ducts (p£0.05) and lower global levels of H3K27me3 in the mammary gland (p£0.05) when compared to CO offspring. No differences (p³0,05) were observed between OB and OJ female offspring regarding these parameters. Consumption of orange juice by non-obese fathers during preconception increased susceptibility of female offspring to mammary carcinogenesis. Although paternal consumption of a high-fat/high-sugar diet during preconception decreased incidence and increased latency of tumors, the multiplicity of lesions increased. In addition, the data indicates that the response to orange juice consumption depends of the paternal metabolic context.