Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets.

Leena Hilakivi-Clarke,Camile Castilho Fontelles,Luiza Nicolosi Guido,Vanessa Cardoso Pires,Fábia de Oliveira Andrade,Lu Jin,Thomas Prates Ong,Sonia de Assis,Jessica Inchauspe,Mariana Papaléo Rosim,Inar Alves de Castro

doi:10.1186/s13058-016-0729-x

Leena Hilakivi-Clarke, Camile Castilho Fontelles + Show 9 more

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https://doi.org/10.1186/s13058-016-0729-x

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Abstract

BackgroundAlthough 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.MethodsMale 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.ResultsCompared 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.ConclusionsOur findings highlight the importance of paternal nutrition in affecting future generations’ risk of developing breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0729-x) contains supplementary material, which is available to authorized users.

Highlights

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
We show that paternal consumption of these high-fat diets elicited opposing effects, with animal fat increasing and vegetable oil decreasing breast cancer risk in the offspring
Compared with control diet-fed male rats, the ones that were on the lard- or corn oil-based high-fat diets consumed more (p ≤ 0.05) SFA, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) (Fig. 1a)

Summary

Introduction

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. The precise reason for this growth is still not clear, it has been suggested that modern women’s lifestyles, including postponing first pregnancy and having fewer children, can explain the increase [3]. Nutritional habits, such as adoption of Western dietary patterns, are linked to increased breast cancer risk [4]. The developmental origins of this cancer have been considered predominantly from a maternal perspective, with emphasis placed on the impact of high fat or energy intake during gestation and lactation on female offspring mammary gland development and later breast cancer risk [8, 9]

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