A1 Refereed original research article in a scientific journal
Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
Authors: Fontelles Camile C., da Cruz Raquel Santana, Gonsiewski Alexandra K., Barin Ersilia, Tekmen Volkan, Jin Lu, Cruz M. Idalia, Loudig Olivier, Wärri Anni, de Assis Sonia
Publisher: NATURE RESEARCH
Publication year: 2021
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 7317
Volume: 11
Number of pages: 13
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-86548-w
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/54714957
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.
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