Maternal dietary exposure to fiber during pregnancy and mammary tumorigenesis among rat offspring

Abstract

Maternal diet during pregnancy has been proposed to modify female offspring's later susceptibility to develop breast cancer; however, most of the dietary factors identified thus far have led to increased risk. To identify dietary factors that might reduce offspring's breast cancer risk, pregnant rat dams were fed diets containing 6% fiber originating either from cellulose (control), or oat, whole wheat or defatted flax flour. At birth, dams were switched to the AIN93 semi-purified diet. Mammary tumor incidence and multiplicity, induced by administering the offspring 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) at the age of 50 days, was reduced in the whole wheat flour-exposed offspring and increased in the defatted flax-exposed offspring. To identify the mechanisms mediating the effects of in utero dietary exposures, changes in mammary gland morphology and gene expression were assessed before puberty onset (3 weeks of age) and at the time rats are most susceptible to malignant transformation (8 weeks of age). The number of terminal end buds (TEBs), i.e., the targets of malignant transformation, was reduced in the mammary glands of whole wheat-and oat flour-exposed offspring, as compared to the controls. Further, the number of apoptotic epithelial cells (based on ISOL assay) was elevated in the whole wheat flour offspring, but no changes in cell proliferation (PCNA), estrogen receptor a (ERa) or cyclin D1 mRNA or protein levels were seen. The mRNA and/or protein levels of BRCA1 and p53 were significantly increased in the mammary glands of whole wheat flour offspring. Further, the levels of 8-hydroxy-2 0 -deoxyguanosine (8-OHdG), a marker of DNA damage, were significantly reduced in these rats, suggesting that maternal dietary exposure to whole wheat during pregnancy may reduce offspring's breast cancer risk by improving DNA damage repair mechanisms. ' 2006 Wiley-Liss, Inc.

Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesis

“…In humans, breast cancer risk is elevated in women who had a high birth weight (12)(13)(14). Animal studies have shown that maternal dietary exposures to a high fat diet (15) or genistein (16) increase, while whole wheat flour (17) or n-3 PUFA (18) reduce female offspring's later mammary tumorigenesis. Maternal dietary exposures during lactation (19) also modify offspring's breast cancer risk.…”

Effects of Maternal Exposure to Cow's Milk High or Low in Isoflavones on Carcinogen-Induced Mammary Tumorigenesis among Rat Offspring

“…Maternal dietary intake of excess fat or other dietary factors during pregnancy have been shown to affect female offspring's later susceptibility to develop mammary cancer in rats (10)(11)(12). This increase in risk is thought to occur due to an increase in fetal estrogenic environment caused by the maternal diet (33,34).…”

“…Results from animal studies suggest that maternal dietary or hormonal exposures during pregnancy may have longlasting effects on mammary tumorigenesis among the female offspring (9)(10)(11)(12). For example, maternal exposure to a high-fat diet during pregnancy increases a female offspring's susceptibility to develop carcinogen-induced mammary tumors in rats (9,13), whereas whole wheat flour, containing lignans, and fish oil reduces the risk (10,12).…”

“…For example, maternal exposure to a high-fat diet during pregnancy increases a female offspring's susceptibility to develop carcinogen-induced mammary tumors in rats (9,13), whereas whole wheat flour, containing lignans, and fish oil reduces the risk (10,12). The effects of maternal exposure to the isoflavone genistein during pregnancy on offspring's mammary tumorigenesis have also been intensively studied but results are conflicting (14).…”

Importance of optimal fiber consumption duringpregnancy

“…Excess of fiber is not recommended because it causes nutrient loss and diarrhea during pregnancy. Fiber is effective in prevention of many GI diseases and cancer (11). Fiber rich diet gives optimal calorie control and early satiety in weight loss plans.…”