Dose‐dependent effects of isoflavone exposure during early lifetime on the rat mammary gland: Studies on estrogen sensitivity, isoflavone metabolism, and DNA methylation

Blei, T.; Soukup, Sebastian T.; Schmalbach, Katja; Pudenz, Maria; Möller, Frank; Egert, Björn; Wörtz, Nadine; Kurrat, Anne; Müller, Dennis R.; Vollmer, Günter; Gerhäuser, Clarissa; Lehmann, Leane; Kulling, Sabine E.; Diel, Patrick

doi:10.1002/mnfr.201400480

Cited by 31 publications

(28 citation statements)

References 57 publications

(71 reference statements)

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“…PhyEs exposure during adolescence modulated the adult mammary gland sensitivity to E 2 and lifelong exposure resulted in dose-dependent differential effects on proliferation, gene expression, and DNA methylation in rat mammary glands. Further studies will be necessary to clarify their effective role, considering that response varies from different race and ethnicity (Blei et al, 2015). The preventive role of PhyEs if assumed during adolescence was also supported by the result of a study showing that intake of PhyEs during adolescence among Ontario women was associated with a reduced risk of developing breast cancer (Anderson et al, 2013).…”

Section: Natural Xenoestrogensmentioning

confidence: 99%

Risks and benefits related to alimentary exposure to xenoestrogens

Paterni

Granchi

Minutolo

2017

Critical Reviews in Food Science and Nutrition

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Xenoestrogens are widely diffused in the environment and in food, thus a large portions of human population is worldwide exposed to them. Among alimentary xenoestrogens, phytoestrogens (PhyEs) are increasingly being consumed because of their potential health benefits, although there are also important risks associated to their ingestion. Furthermore, other xenoestrogens that may be present in food are represented by other chemicals possessing estrogenic activities, that are commonly defined as endocrine disrupting chemicals (EDCs). EDCs pose a serious health concern since they may cause a wide range of health problems, starting from pre-birth till adult lifelong exposure. We herein provide an overview of the main classes of xenoestrogens, which are classified on the basis of their origin, their structures and their occurrence in the food chain. Furthermore, their either beneficial or toxic effects on human health are discussed in this review.

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Section: Natural Xenoestrogensmentioning

confidence: 99%

Risks and benefits related to alimentary exposure to xenoestrogens

Paterni

Granchi

Minutolo

2017

Critical Reviews in Food Science and Nutrition

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“…Isoflavones appear to modulate epigenetic mechanisms, including DNA methylation, histone modifying genes and noncoding RNAs [38]. Some of the genes suffering DNA methylation, after exposure to high or low doses of isoflavones [39], regulate the proliferation of mammary epithelial cells. Our study has effectively demonstrated the differential expression of a proliferation marker in castrated rats induced by isoflavones.…”

Section: Discussionmentioning

confidence: 99%

“…A clear dose response pattern cannot always be observed [39]. According Blei et al, an isoflavone dose that reflects a lifelong nutritional exposure via a soy rich diet may be sufficient to result in an increase in fat metabolism, protein synthesis and skeletal muscle mass.…”

Section: Discussionmentioning

confidence: 99%

Effects of ovariectomy, estrogen and soy isoflavones in rats submandibular glands

Vasconcellos

Silveira

Medeiros

et al. 2017

BDS

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110 ResumoObjetivo: Diminuição das células granulares do túbulo contorcido granular e dos ácinos ocorre nas glândulas submandibulares de ratas fêmeas ovariectomizadas, enquanto que nas ratas submetidas a reposição hormonal e fitoterapia com isoflavona da soja, este efeito é revertido. Este estudo tem como objetivo elucidar os mecanismos pelo qual estas alterações ocorrem. Material e Métodos: 84 ratas foram ovariectomizadas e 21 foram sham-operatadas. As ratas ovariectomizadas foram aleatoriamente subdivididas e receberam administração oral dos seguintes medicamentos: 17 β-estradiol (OVX-E; n=21), 15 mg/ kg/day do extrato de isoflavona da soja (OVX-I; n=21), 17 β-estradiol + extrato de isoflavona da soja (OVX-A; n=21); e água como placebo (OVX; n=21). As ratas foram eutanasiadas 3, 5 e 8 semanas após a ovariectomia. As glândulas submandibulares foram submetidas a análise histológica por meio do processamento histológico de coloração com HE e imunohistoquímica utilizando o complexo peroxidase-biotina-streptavidina. A área celular e a expressão do antígeno de proliferação celular nuclear e receptor β estrogênico foram avaliados. Resultados: Os resultados foram estatisticamente analisados por meio do teste ANOVA e Tukey. Foi observada diminuição na área de células GCT cells no grupo OVX, em contraste com o aumento no grupoe OVX-E. PCNA nas células acinares e receptores de estrógeno estavam aumentados no grupo OVX-I. Conclusão: A castração exerce um efeito indutivo imediato no volume das células GCT. Estrógeno, isoflavona da soja e sua combinação têm diferentes mecanismos de ação sobre a homeostase da glândula. Estrógeno causa um aumento da área de células GCT, enquanto a isoflavona aumenta a proliferação celular e a expressão do receptor-β de estrógeno. A associação destes não mostrou aumento adicional nos efeitos estudados. ABsTRACTObjective: A decrease in granular convoluted tubule (GCT) cells and acini occurs in the submandibular glands of castrated female rats, while in rats submitted to hormone replacement and phytotherapy with soy isoflavones, this effect is reversed. This study aimed to elucidate the mechanisms through which these changes occur. Material and Methods: Rats (n=84) were ovariectomized and 21 were sham-operated. Ovariectomized rats were randomly subdivided and orally administered the following: 17 β-estradiol (OVX-E; n=21), 15 mg/kg/day of soy isoflavone extract (OVX-I; n=21), 17 β-estradiol + soy isoflavone extract (OVX-A; n=21); and water as placebo (OVX; n=21). The rats were euthanized three, five and eight weeks after ovariectomy. The submandibular salivary glands were submitted to histological processing with HE stain and immunohistochemistry was performed using the streptavidin-biotinperoxidase complex. The cell area and the expression of proliferating cell nuclear antigen and estrogen receptor β were evaluated. Results: The results were statistically analyzed by ANOVA and Tukey test. A decrease in the area of GCT cells in the OVX, was observed, in contrast with an increase in the OVX-E. PC...

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“…Details and permission for the soy intervention study in rats are described in ref. [42]. Details and ethical approval for the human broccoli intervention study are described in ref.…”

Section: Compliance With Ethics Guidelinesmentioning

confidence: 99%

“…One of the aims in this project is to investigate the influence soy isoflavones on estrogen sensitivity of mammary glands [42]. Isoflavones are phyto-estrogenic plant compounds and could therefore attenuate physiological changes associated with hormone deprivation [43].…”

Section: Mcip-seq After Dietary Soy Intervention In Healthy Wistar Ratsmentioning

confidence: 99%

Genome-Wide DNA Methylation Profiling in Dietary Intervention Studies: a User’s Perspective

2015

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Within the past decade, epigenetic mechanisms and their modulation by dietary agents have gained major interest in the cancer prevention and nutrition community. Gene expression is epigenetically regulated by DNA methylation, histone tail modifications, and non-coding (micro) RNAs. Given the fact that epigenetic aberrations are reversible and represent potentially initiating events in the development of diseases, they have been identified as promising new targets for prevention strategies. Evidence is accumulating that dietary cancer chemopreventive agents from various sources, including green tea, soy, turmeric, broccoli, and other fruit and vegetables, can modulate DNA methylation, at least in vitro. To facilitate in vivo studies with focus on genomewide modulation of DNA methylation, we here give an overview on current affinity enrichment-and bisulfite treatmentbased methodologies for methylation profiling that might be useful for rodent models and human intervention studies. We also summarize genome-wide methylome analyses performed with dietary agents in vitro and in vivo and conclude with some practical considerations for the design of future dietary intervention studies.

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Dose‐dependent effects of isoflavone exposure during early lifetime on the rat mammary gland: Studies on estrogen sensitivity, isoflavone metabolism, and DNA methylation

Abstract: Lifelong exposure to ISO results in dose-dependent differential effects on proliferation, gene expression, and DNA methylation in rat mammary glands. Yet, a decrease in estrogen responsiveness was only achieved by IRDhigh.

Cited by 31 publications

References 57 publications

Risks and benefits related to alimentary exposure to xenoestrogens

Risks and benefits related to alimentary exposure to xenoestrogens

Effects of ovariectomy, estrogen and soy isoflavones in rats submandibular glands

Genome-Wide DNA Methylation Profiling in Dietary Intervention Studies: a User’s Perspective

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