A maternal diet high in n - 6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring

Leena Hilakivi-Clarke, Robert Clarke, Ighovie Onojafe, Margarita Raygada, Elizabeth Cho, Marc E Lippman

Research output: Contribution to journalArticle

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Abstract

We hypothesized that feeding pregnant rats with a high-fat diet would increase both circulating 17β-estradiol (E2) levels in the dams and the risk of developing carcinogen-induced mammary tumors among their female offspring. Pregnant rats were fed isocaloric diets containing 12% or 16% (low fat) or 43% or 46% (high fat) of calories from corn oil, which primarily contains the n 6 polyunsaturated fatty acid (PUFA) linoleic acid, throughout pregnancy. The plasma concentrations of E2 were significantly higher in pregnant females fed a high n 6 PUFA diet. The female offspring of these rats were fed with a laboratory chow from birth onward, and when exposed to 7,12- dimethylbenz(a)anthracene had a significantly higher mammary tumor incidence (60% vs. 30%) and shorter latency for tumor appearance (11.4 ± 0.5 weeks vs. 14.2 ± 0.6 weeks) than the offspring of the low-fat mothers. The high-fat offspring also had puberty onset at a younger age, and their mammary glands contained significantly higher numbers of the epithelial structures that are the targets for malignant transformation. Comparable changes in puberty onset, mammary gland morphology, and tumor incidence were observed in the offspring of rats treated daily with 20 ng of E2 during pregnancy. These data, if extrapolated to humans, may explain the link among diet, early puberty onset, mammary parenchymal patterns, and breast cancer risk, and indicate that an in utero exposure to a diet high in n 6 PUFA and/or estrogenic stimuli may be critical for affecting breast cancer risk.

Original languageEnglish
Pages (from-to)9372-9377
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number17
DOIs
StatePublished - Aug 19 1997
Externally publishedYes

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Human Mammary Glands
Puberty
Fats
Mothers
Breast Neoplasms
Diet
Unsaturated Fatty Acids
Pregnancy
Corn Oil
Incidence
High Fat Diet
Linoleic Acid
Carcinogens
Estradiol
Breast
Parturition
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

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A maternal diet high in n - 6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring. / Hilakivi-Clarke, Leena; Clarke, Robert; Onojafe, Ighovie; Raygada, Margarita; Cho, Elizabeth; Lippman, Marc E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 17, 19.08.1997, p. 9372-9377.

Research output: Contribution to journalArticle

Hilakivi-Clarke, Leena ; Clarke, Robert ; Onojafe, Ighovie ; Raygada, Margarita ; Cho, Elizabeth ; Lippman, Marc E. / A maternal diet high in n - 6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 17. pp. 9372-9377.
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