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

Abstract

Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 21) might affect 7,12-dimethylbenz[a]anthracene (DMBA) -induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-α protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-β protein levels in the lobules and terminal end buds (TEBs). Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the TEBs, lobules or ducts. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was 7-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-β content was causally linked to increased mammary cancer risk among the offspring.

Effect of Maternal and Postweaning Folic Acid Supplementation on Mammary Tumor Risk in the Offspring

“…Another potential explanation for the contradictory finding between these studies is that terminal end bud density at puberty may not be a consistent predictor of mammary tumor risk in rodents as suggested by recent studies (40,41).…”

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).…”

Herbal laxatives and antiemetics in pregnancy

“…It was found that after the administration of different doses of FEO (10,20,25,40 and 50 g/ml), the oxytocin (0.1, 1 and 10 mU/ml) -and prostaglandin E2 (5 × 10 −5 M) -induced contractions were reduced significantly. The estimated LD 50 was 1326 mg/kg for FEO.…”

“…The maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 25) might affect 7,12 dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the rat offspring. It is proclaimed that both in utero and postnatal 5% and 10% flaxseed exposures can shorten mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls [25].…”