High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring

Sonia De Assis, Anni Warri, M. Idalia Cruz, Olusola Laja, Ye Tian, Bai Zhang, Yue Wang, Hui-ming Huang, Leena Hilakivi-Clarke

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Maternal exposures to environmental factors during pregnancy influence the risk of many chronic adult-onset diseases in the offspring. Here we investigate whether feeding pregnant rats a high-fat (HF)-or ethinyl-oestradiol (EE2)-supplemented diet affects carcinogen-induced mammary cancer risk in daughters, granddaughters and great-granddaughters. We show that mammary tumourigenesis is higher in daughters and granddaughters of HF rat dams and in daughters and great-granddaughters of EE2 rat dams. Outcross experiments suggest that the increase in mammary cancer risk is transmitted to HF granddaughters equally through the female or male germ lines, but it is only transmitted to EE2 granddaughters through the female germ line. The effects of maternal EE2 exposure on offspring's mammary cancer risk are associated with changes in the DNA methylation machinery and methylation patterns in mammary tissue of all three EE2 generations. We conclude that dietary and oestrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic means.

Original languageEnglish (US)
Article number1053
JournalNature Communications
Volume3
DOIs
StatePublished - 2012

Fingerprint

Ethinyl Estradiol
pregnancy
fats
cancer
Fats
Breast Neoplasms
Pregnancy
rats
Maternal Exposure
Rats
methylation
dams
Germ Cells
Dams
Breast
carcinogens
diets
Methylation
machinery
DNA Methylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring. / De Assis, Sonia; Warri, Anni; Cruz, M. Idalia; Laja, Olusola; Tian, Ye; Zhang, Bai; Wang, Yue; Huang, Hui-ming; Hilakivi-Clarke, Leena.

In: Nature Communications, Vol. 3, 1053, 2012.

Research output: Contribution to journalArticle

De Assis, Sonia ; Warri, Anni ; Cruz, M. Idalia ; Laja, Olusola ; Tian, Ye ; Zhang, Bai ; Wang, Yue ; Huang, Hui-ming ; Hilakivi-Clarke, Leena. / High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring. In: Nature Communications. 2012 ; Vol. 3.
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AU - Tian, Ye

AU - Zhang, Bai

AU - Wang, Yue

AU - Huang, Hui-ming

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