A MATERNAL DIET HIGH IN N-6 POLYUNSATURATED FATS ALTERS MAMMARY-GLANDDEVELOPMENT, PUBERTY ONSET, AND BREAST-CANCER RISK AMONG FEMALE RAT OFFSPRING

We hypothesized that feeding pregnant rats with a high-fat diet would increase both circulating 17 beta-estradiol (E2) levels in the darns a nd the risk of developing carcinogen-induced mammary tumors among thei r female offspring. Pregnant rats were fed isocaloric diets containing 12% or 16% (ion-fat) or 43% or 46% (high fat) of calories from corn o il, which primarily contains the n - 6 polyunsaturated fatty acid (PUF A) Linoleic acid, throughout pregnancy, The plasma concentrations of E 2 were significantly higher in pregnant females fed a high n - 6 PUFA diet, The female offspring of these rats were fed with a laboratory ch ow from birth onward, and when exposed to 7,12-dimethylbenz(a) anthrac ene had a significantly higher mammary tumor incidence (60% vs. 30%) a nd 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 g lands contained significantly higher numbers of the epithelial structu res that are the targets for malignant transformation. Comparable chan ges in puberty onset, mammary gland morphology, and tumor incidence me re observed in the offspring of rats treated daily with 20 ng of E2 du ring pregnancy, These data, if extrapolated to humans, may explain the link among diet, early puberty onset, mammary parenchymal patterns, a nd breast cancer risk, and indicate that an in utero exposure to a die t high in n - 6 PUFA and/or estrogenic stimuli may-be critical for aff ecting breast cancer risk.