The present study investigated whether early life exposure to high levels of animal fat increases
breast cancer risk in adulthood in rats. Dams consumed a
lard-based high-fat (HF) diet (60% fat-derived energy) or an AIN93G control diet (16% fat-derived energy) during gestation or gestation and lactation. Their 7-week-old female offspring were exposed to 7,12-dimethyl-
benzo[a]anthracene to induce mammary
tumors. Pregnant dams consuming an HF diet had higher circulating
leptin levels than pregnant control dams. However, compared to the control offspring, significantly lower susceptibility to
mammary cancer development was observed in the offspring of dams fed an HF diet during pregnancy (lower
tumor incidence, multiplicity and weight), or pregnancy and lactation (lower
tumor multiplicity only). Mammary epithelial elongation, cell proliferation (Ki67) and expression of NFκB p65 were significantly lower and p21 expression and global H3K9me3 levels were higher in the mammary glands of rats exposed to an HF
lard diet in utero. They also tended to have lower Rank/Rankl ratios (P=.09) and serum
progesterone levels (P=.07) than control offspring. In the mammary glands of offspring of dams consuming an HF diet during both pregnancy and lactation, the number of terminal end buds, epithelial elongation and the BCL-2/BAX ratio were significantly lower and serum
leptin levels were higher than in the controls. Our data confirm that the
breast cancer risk of offspring can be programmed by maternal dietary intake. However, contrary to our expectation, exposure to high levels of
lard during early life decreased later susceptibility to
breast cancer.