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Title: In utero and lactational exposure to blueberry via maternal diet promotes mammary epithelial differentiation in prepubescent female rats

item WU, XIANLI - Arkansas Children'S Nutrition Research Center (ACNC)
item RAHAL, OMAR - Arkansas Children'S Nutrition Research Center (ACNC)
item KANG, JIE - Arkansas Children'S Nutrition Research Center (ACNC)
item TILL, SHARON - Arkansas Children'S Nutrition Research Center (ACNC)
item Prior, Ronald
item SIMMEN, ROSALIA - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/11/2009
Publication Date: 11/15/2009
Citation: Wu, X., Rahal, O., Kang, J., Till, S.R., Prior, R.L., Simmen, R.C. 2009. In utero and lactational exposure to blueberry via maternal diet promotes mammary epithelial differentiation in prepubescent female rats. Nutrition Research. 29(11):802-811.

Interpretive Summary: Consumption of fruits is considered good nutritional practice for overall health and prevention of many diseases. Pregnant and breast-feeding mothers are advised to eat healthy diets consisting of at least 5-6 daily servings of fruits and vegetables. However, the scientific basis for this recommendation is not well-explored. In this study, we examined if dietary intake of blueberry by pregnant and lactating rats affects mammary gland development of female offspring. We found that pups of dams consuming blueberry have increased mammary gland development predictive of decreased risk for breast cancer. These findings provide a strong rationale for good nutrition in women during pregnancy and while breast-feeding and suggest that what mothers eat can affect the health status of the next generation.

Technical Abstract: Early developmental events influence the fine tuning of later susceptibility to adult diseases. Diet is a determinant of breast cancer risk, and our previous studies showed that diet-mediated changes in transcriptional programs promote early mammary gland differentiation. While consumption of fruits is considered to elicit multiple health benefits, little is known on whether associated bioactive components modify the early differentiation program in developing mammary glands. Here, we evaluated the hypothesis that early exposure (in utero and lactational) to blueberry through maternal diet enhances mammary epithelial differentiation in female offspring. Pregnant Sprague-Dawley rats beginning at gestation day 4 were fed American Institute of Nutrition-based diets containing casein and whole blueberry powders added to casein at 2.5, 5.0, and 10 % weight/weight. Female pups at weaning were evaluated for growth and mammary tissue parameters. Blueberry at 5 % dose increased body and adipose fat weights, relative to the other diets. Mammary branch density and terminal end bud size were highest for the 5 % blueberry group, while terminal end bud numbers were not affected by all diets. Mammary ductal epithelial cells of the 5 % blueberry group had lower nuclear phosphorylated Histone 3 and higher nuclear tumor suppressor Phosphatase and Tensin homolog deleted in Chromosome Ten (PTEN) levels than casein group. While sera of both diet groups had similar anti-oxidant capacity, 5 % blueberry sera elicited higher nuclear PTEN accumulation in human MCF-10A mammary epithelial cells. Our studies identify developing mammary glands as early targets of blueberry-associated bioactive components, possibly through systemic effects on epithelial PTEN signaling.