Gestational high-fat diet and bisphenol A exposure heightens mammary cancer risk

Abstract

In utero exposure to bisphenol A (BPA) increases mammary cancer susceptibility in offspring. High-fat diet is widely believed to be a risk factor of breast cancer. The objective of this study was to determine whether maternal exposure to BPA in addition to high-butterfat (HBF) intake during pregnancy further influences carcinogen-induced mammary cancer risk in offspring, and its dose–response curve. In this study, we found that gestational HBF intake in addition to a low-dose BPA (25 µg/kg BW/day) exposure increased mammary tumor incidence in a 50-day-of-age chemical carcinogen administration model and altered mammary gland morphology in offspring in a non-monotonic manner, while shortening tumor-free survival time compared with the HBF-alone group. In utero HBF and BPA exposure elicited differential effects at the gene level in PND21 mammary glands through DNA methylation, compared with HBF intake in the absence of BPA. Top HBF + BPA-dysregulated genes (ALDH1B1, ASTL, CA7, CPLX4, KCNV2, MAGEE2 and TUBA3E) are associated with poor overall survival in The Cancer Genomic Atlas (TCGA) human breast cancer cohort (n = 1082). Furthermore, the prognostic power of the identified genes was further enhanced in the survival analysis of Caucasian patients with estrogen receptor-positive tumors. In conclusion, concurrent HBF dietary and a low-dose BPA exposure during pregnancy increases mammary tumor incidence in offspring, accompanied by alterations in mammary gland development and gene expression, and possibly through epigenetic reprogramming.

Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health

“…An abnormal increase in insulin secretion in the lower BPA group is likely to eventually lead to exhaustion of 50 This is further supported by data from human and animal studies showing that a constant increase in insulin secretion can lead to mitochondrial dysfunction and endoplasmic reticulum stress, which leads to cellular injury and a progressive decline in β-cell function (i.e., βcell exhaustion). 51,52 Furthermore, the third-generation animals of the current study may display an altered metabolic response, if challenged by a second insult such as a high-fat diet as reported in pancreas 53 and other target tissues like mammary gland, sperm and liver [54][55][56] of the first-generation offspring. This requires further investigation.…”

Prognostic roles of MAGE family�members in breast cancer based on KM‑Plotter Data

“…High mRNA expression levels of MAGEE1 were significantly associated with improved RFS in grade I and basal-like 2 breast cancer, but also with worse RFS in grade III and mesenchymal breast cancer; high mRNA expression levels of MAGEE2 were significantly associated with improved RFS in basal, lymph node-negative and mesenchymal stem-like breast cancer, but also with worse RFS in TP53 wild-type breast cancer. MAGEE2 expression has been reported to be associated with poor OS in The Cancer Genome Atlas human breast cancer cohort (n=1,082) (49). In general, these findings indicated that MAGEE2 was closely associated with the occurrence and development of breast cancer, particularly in TP53 wild-type breast cancer.…”

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

“…Dietary exposure to BPA in the Agouti viable yellow (A(vy)) mouse model has been shown to hypomethylate metastable epialleles, an effect that can be counteracted with dietary supplementation of methyl donors or genistein ( 61 ). According to further evidence from animal models, antenatal and perinatal BPA exposure has been found to lead to specific epigenetic changes, resulting, among the others, in impaired stress response ( 62 ) and higher rates of mammary cancer ( 63 ); this contributes to highlight the clinical burden associated with chemical food contamination.…”