Effects of Maternal Grape Juice Intake on Unfolded Protein Response in the Mammary Glands of Offspring of High Fat Diet Fed Rat Dams.

Caroline Dani,Luciana Kneib Gonçalves,Leena Hilakivi-Clarke,Fabia De Oliveira Andrade,Isabel Teixeira Proença

doi:10.3390/nu12082253

Caroline Dani, Luciana Kneib Gonçalves + Show 3 more

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https://doi.org/10.3390/nu12082253

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Abstract

Maternal high fat diet (HFD) and obesity during pregnancy increase female offspring′s mammary cancer risk in animal studies. We aimed to observe whether the consumption of grape juice during pregnancy can reverse this risk. During pregnancy and lactation, female Wistar rats were fed either a control or HFD and also received grape juice or tap water. At the age of 50 days, female offspring were euthanized, and mammary glands were collected to assess changes in biomarkers of increased mammary cancer risk. Maternal HFD increased the number of terminal end buds in offspring’s mammary glands and promoted cell proliferation (ki67). Maternal grape consumption blocked these effects. Apoptosis marker caspase 7, but not caspase 3, was reduced in the HFD offspring. HFD offspring also exhibited a reduction in the indicators of cell cycle regulation (p27, p21) and an ability to maintain DNA integrity (reduced p53). Maternal grape juice did not have any effect on these endpoints in the HFD offspring but reduced caspase 7 and p53 levels in the control offspring, perhaps reflecting reduced cellular stress. Maternal HFD increased oxidative stress marker GPx1 mRNA expression, and grape juice increased the levels of GPx2 in both the control and HFD offspring. HFD increased XBP1/Xbp1s, Atf4 and Atf6 mRNA expression and reduced ATF6 and CHOP protein levels. Maternal grape juice reversed the increase in XBP1/Xbp1s, Atf4 and Atf6 in the HFD offspring. PPARγ was downregulated in the HFD group, and grape juice reversed this effect. Grape juice also reduced the levels of HER2 and IRS, both in the control and HFD offspring. In conclusion, maternal grape juice supplementation reversed some of the biomarkers that are indicative of increased breast cancer risk in the HFD offspring.

Highlights

Breast cancer is the most common invasive cancer among women, comprising 30% of all female cancers in the United States [1]
Maternal grape juice supplementation reversed some of the biomarkers that are indicative of increased breast cancer risk in the high fat diet (HFD) offspring
Since an increase in terminal end buds (TEBs) at the age of 50 days in rats is associated with increased mammary cancer risk [40], our results suggest that HFD offspring were at increased mammary cancer risk and maternal grape juice intake prevented this increase

Summary

Introduction

Breast cancer is the most common invasive cancer among women, comprising 30% of all female cancers in the United States [1]. The incidence of breast cancer varies in different regions across the world. In Asian countries, the cumulative risk of developing breast cancer at the age of 75 is. 3.0%, whilst in the U.S, it is 10.0% [2]. The differences in risk are not caused by ethnicity: over two generations, descendants of Asians who migrated to the west have acquired the same breast cancer incidence as the population of the host country [3,4]. Environmental and lifestyle factors may have a major role in determining breast cancer risk. Several studies indicate that maternal diet during pregnancy alters daughters0 breast cancer risk

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