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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-86548-w |
| _version_ | 1818749666136686592 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:07:24Z |
| format | Article |
| id | doaj.art-9320a5d49cd74380a28f30c854e99566 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:07:24Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9320a5d49cd74380a28f30c854e995662022-12-21T21:21:34ZengNature PortfolioScientific Reports2045-23222021-04-0111111310.1038/s41598-021-86548-wSystemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generationCamile C. Fontelles0Raquel Santana da Cruz1Alexandra K. Gonsiewski2Ersilia Barin3Volkan Tekmen4Lu Jin5M. Idalia Cruz6Olivier Loudig7Anni Warri8Sonia de Assis9Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityInstitute of Biomedicine, University of Turku Medical FacultyDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityAbstract 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.https://doi.org/10.1038/s41598-021-86548-w |
| spellingShingle | 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 Scientific Reports |
| 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_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_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_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 |
| url | https://doi.org/10.1038/s41598-021-86548-w |
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