title: Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets.
abstract: Although males contribute half of the embryo's genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter's breast cancer risk has been examined in few studies.
  
  
  
  Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis.
  
  
  
  Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers' sperm and their daughters' mammary glands, and to modifications in breast cancer-related protein expression in this tissue.
  
  
  
  Our findings highlight the importance of paternal nutrition in affecting future generations' risk of developing breast cancer.
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil.
authors.forename: Camile Castilho
authors.initials: CC
authors.lastname: Fontelles
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil.
authors.forename: Luiza Nicolosi
authors.initials: LN
authors.lastname: Guido
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil.
authors.forename: Mariana Papaléo
authors.initials: MP
authors.lastname: Rosim
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil.
authors.forename: Fábia de Oliveira
authors.initials: Fde O
authors.lastname: Andrade
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, 20007, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, 20007, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Inchauspe
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil.
authors.forename: Vanessa Cardoso
authors.initials: VC
authors.lastname: Pires
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil.
authors.forename: Inar Alves
authors.initials: IA
authors.lastname: de Castro
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, 20007, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Hilakivi-Clarke
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, 20007, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: de Assis
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, Bloco 14, São Paulo, SP, 05508-000, Brazil. tong@usp.br.|Food Research Center (FoRC), São Paulo, 05508-000, Brazil. tong@usp.br.
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016000:Cluster Analysis; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal; D008325:Mammary Neoplasms, Experimental; D008460:Meat; D035683:MicroRNAs; D018812:Paternal Exposure; D010944:Plants / Q000737:chemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D040901:Proteomics / Q000379:methods; D051381:Rats; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D008055:Lipids; D035683:MicroRNAs
keywords: Breast cancer; Female offspring; High-fat diet; Paternal diet