scholarly journals Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

2016 ◽  
Vol 303 ◽  
pp. 101-109 ◽  
Author(s):  
Tony F. Grassi ◽  
Glenda N. da Silva ◽  
Lucas T. Bidinotto ◽  
Bruna F. Rossi ◽  
Marília M. Quinalha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Bisphenol A ◽  
Global Gene Expression ◽  
Sprague Dawley ◽  
Morphological Alterations ◽  
Gestational Exposure

scholarly journals Mammary gland morphological and gene expression changes underlying pregnancy protection of breast cancer tumorigenesis

2012 ◽  
Vol 44 (1) ◽  
pp. 76-88 ◽  
Author(s):  
Yogi Misra ◽  
Pamela A. Bentley ◽  
Jeffrey P. Bond ◽  
Scott Tighe ◽  
Timothy Hunter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Mammary Gland ◽  
Global Gene Expression ◽  
Full Term ◽  
Mammary Tissue ◽  
Protective Mechanism ◽  
Global Changes ◽  
Term Pregnancy ◽  
Short Term Treatment

A full-term pregnancy early in life reduces lifetime risk of developing breast cancer, and the effect can be mimicked in rodents by full-term pregnancy or short-term treatment with exogenous estrogen and progesterone. To gain insight into the protective mechanism, 15 3-mo-old postpubertal virgin Lewis rats were randomly assigned to three groups: control (C), pregnancy (P), or hormone (H). The P group animals underwent a full-term pregnancy, and H group animals were implanted subcutaneously with silastic capsules filled with ethynyl estradiol and megesterol acetate for 21 days. C and P animals were implanted with sham capsules. On day 21 capsules were removed, which was followed by a 49-day involution period, euthanasia, and mammary tissue collection. Global gene expression was measured using Rat Genome 230.2 Arrays. Histological analysis revealed that P and H treatments induced sustained morphological changes in the mammary gland with significantly increased percentages of mammary parenchyma and stromal tissues and higher ratio of stroma to parenchyma. Transcriptome analysis showed that P and H treatments induced sustained global changes in gene expression in the mammary gland. Analysis of commonly up- and downregulated genes in P and H relative to C treatment showed increased expression of three matrix metallopeptidases (Mmp3, 8, and 12), more differentiated mammary phenotype, enhanced innate and adaptive immunity, and reduced cell proliferation and angiogenic signatures. The sustained morphological and global gene expression changes in mammary tissue after pregnancy and hormone treatment may function together to provide the protective effect against breast cancer.

scholarly journals A gestational low-protein diet represses p21WAF1/Cip1 expression in the mammary gland of offspring rats through promoter histone modifications

2011 ◽  
Vol 108 (6) ◽  
pp. 998-1007 ◽  
Author(s):  
Shasha Zheng ◽  
Michelle Rollet ◽  
Kefeng Yang ◽  
Yuan-Xiang Pan
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Histone Modifications ◽  
Promoter Region ◽  
Kinase Inhibitor ◽  
Protein Restriction ◽  
Histone H4 ◽  
Sprague Dawley ◽  
Low Protein ◽  
Maternal Protein Restriction

Maternal exposure to environmental agents throughout pregnancy may change certain metabolic processes during the offspring's mammary gland development and alter the epigenome. This may predispose the offspring to breast cancer later in life. The purpose of the present study was to examine the effect of maternal protein restriction on the regulation of cyclin-dependent kinase inhibitor 1 (p21) gene expression in the mammary gland of rat offspring. Timed-mated Sprague–Dawley rats were fed one of the two isoenergetic diets, control (C, 18 % casein) or low protein (LP, 9 % casein), during gestation. Compared with the C group, LP offspring showed a decrease of p21 in the mammary gland at both the mRNA and protein levels. Chromatin immunoprecipitation assay demonstrated that the down-regulation of p21 transcription in LP offspring was associated with reduced acetylation of histone H3 and dimethylation of H3K4 within the p21 promoter region, but was not associated with acetylation of histone H4 or histone methylation. DNA methylation analysis using bisulphite sequencing did not detect differences in methylation at the p21 promoter between the offspring of the C and LP groups. We conclude that maternal protein restriction inhibits p21 gene expression in the mammary gland of offspring through histone modifications at the promoter region of the p21 gene.

scholarly journals Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature

2007 ◽  
Vol 196 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Raquel Moral ◽  
Richard Wang ◽  
Irma H Russo ◽  
Coral A Lamartiniere ◽  
Julia Pereira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Bisphenol A ◽  
Endocrine Disruptor ◽  
Dose Group ◽  
Low Dose ◽  
Gene Expression Signature ◽  
High Dose ◽  
Proliferative Index ◽  
Induced Changes

Bisphenol A (BPA), known as an environmental endocrine disruptor, is widely used as a plasticizer. This study aims to investigate whether exposure in utero to BPA alters the architecture, proliferative index, and genomic signature of the rat mammary gland during critical stages of development. Pregnant rats were gavaged with 25 μg BPA/kg body weight (BW; low-dose group) or 250 μg BPA/kg BW (high-dose group) from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50, and 100 days, and mammary glands were collected. Analysis of gland morphology was performed from whole-mounted mammary tissue, while proliferative index was determined by detection of bromodeoxyuridine incorporation in the epithelial cells. Genomic profiles were obtained by microarray analysis, and some genes were validated by real-time RT-PCR. BPA exposure induced changes in the mammary gland that were time and dose specific. High-dose exposure resulted in architectural modifications, mainly in the number of undifferentiated epithelial structures of the breast tissue. Proliferative index did not show remarkable differences by the effect of BPA. Low and high doses of BPA changed the gene expression signature of the mammary gland following a different fashion: low dose had the highest effect by 50 days, while high dose had a highest influence on gene expression by 100 days. Both doses presented a significant cluster of up-modulated genes related to the immune system at the age of maximal changes. Moreover, high-dose exposure induced changes in genes related to differentiation suggesting alterations in the normal development of the gland. The increase of undifferentiated structures and the changes in the gene expression profile at different ages suggest that prenatal exposure to BPA can affect the susceptibility of the mammary gland to transformation.

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