Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation

Abstract We previously showed that environmentally-induced epigenetic inheritance of cancer occurs in rodent models. For instance, we reported that paternal consumption of an obesity-inducing diet (OID) increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear w...

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Autores principales:	Camile C. Fontelles, Raquel Santana da Cruz, Alexandra K. Gonsiewski, Ersilia Barin, Volkan Tekmen, Lu Jin, M. Idalia Cruz, Olivier Loudig, Anni Warri, Sonia de Assis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9320a5d49cd74380a28f30c854e99566
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spelling	oai:doaj.org-article:9320a5d49cd74380a28f30c854e995662021-12-02T13:27:08ZSystemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation10.1038/s41598-021-86548-w2045-2322https://doaj.org/article/9320a5d49cd74380a28f30c854e995662021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86548-whttps://doaj.org/toc/2045-2322Abstract We previously showed that environmentally-induced epigenetic inheritance of cancer occurs in rodent models. For instance, we reported that paternal consumption of an obesity-inducing diet (OID) increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether programming of breast cancer in daughters is due to systemic alterations or mammary epithelium-specific factors and whether the breast cancer predisposition in F1 progeny can be transmitted to subsequent generations. In this study, we show that mammary glands from F1 control (CO) female offspring exhibit enhanced growth when transplanted into OID females compared to CO mammary glands transplanted into CO females. Similarly, carcinogen-induced mammary tumors from F1 CO female offspring transplanted into OID females has a higher proliferation/apoptosis rate. Further, we show that granddaughters (F2) from the OID grand-paternal germline have accelerated tumor growth compared to CO granddaughters. This between-generation transmission of cancer predisposition is associated with changes in sperm tRNA fragments in OID males. Our findings indicate that systemic and mammary stromal alterations are significant contributors to programming of mammary development and likely cancer predisposition in OID daughters. Our data also show that breast cancer predisposition is transmitted to subsequent generations and may explain some familial cancers, if confirmed in humans.Camile C. FontellesRaquel Santana da CruzAlexandra K. GonsiewskiErsilia BarinVolkan TekmenLu JinM. Idalia CruzOlivier LoudigAnni WarriSonia de AssisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Camile C. Fontelles Raquel Santana da Cruz Alexandra K. Gonsiewski Ersilia Barin Volkan Tekmen Lu Jin M. Idalia Cruz Olivier Loudig Anni Warri Sonia de Assis Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
description	Abstract We previously showed that environmentally-induced epigenetic inheritance of cancer occurs in rodent models. For instance, we reported that paternal consumption of an obesity-inducing diet (OID) increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether programming of breast cancer in daughters is due to systemic alterations or mammary epithelium-specific factors and whether the breast cancer predisposition in F1 progeny can be transmitted to subsequent generations. In this study, we show that mammary glands from F1 control (CO) female offspring exhibit enhanced growth when transplanted into OID females compared to CO mammary glands transplanted into CO females. Similarly, carcinogen-induced mammary tumors from F1 CO female offspring transplanted into OID females has a higher proliferation/apoptosis rate. Further, we show that granddaughters (F2) from the OID grand-paternal germline have accelerated tumor growth compared to CO granddaughters. This between-generation transmission of cancer predisposition is associated with changes in sperm tRNA fragments in OID males. Our findings indicate that systemic and mammary stromal alterations are significant contributors to programming of mammary development and likely cancer predisposition in OID daughters. Our data also show that breast cancer predisposition is transmitted to subsequent generations and may explain some familial cancers, if confirmed in humans.
format	article
author	Camile C. Fontelles Raquel Santana da Cruz Alexandra K. Gonsiewski Ersilia Barin Volkan Tekmen Lu Jin M. Idalia Cruz Olivier Loudig Anni Warri Sonia de Assis
author_facet	Camile C. Fontelles Raquel Santana da Cruz Alexandra K. Gonsiewski Ersilia Barin Volkan Tekmen Lu Jin M. Idalia Cruz Olivier Loudig Anni Warri Sonia de Assis
author_sort	Camile C. Fontelles
title	Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
title_short	Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
title_full	Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
title_fullStr	Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
title_full_unstemmed	Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
title_sort	systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9320a5d49cd74380a28f30c854e99566
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Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation

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