The role of early life genistein exposures in modifying breast cancer risk

Wärri, Anni; Saarinen, Niina M.; Mäkelä, Sari; Hilakivi‐Clarke, Leena

doi:10.1038/sj.bjc.6604321

Cited by 132 publications

(113 citation statements)

References 51 publications

(74 reference statements)

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“…Environmental chemicals with estrogenic activity (xenoestrogens, such as BPA, and the pesticide, dieldrin) and other EDCs not exhibiting estrogenic behavior (such as dioxin and atrazine) may cause abnormal mammary gland development (Markey et al 2001, Munoz-de-Toro et al 2005, Fenton 2006, Enoch et al 2007, Vandenberg et al 2007 or may increase the risk of breast cancer (Durando et al 2007, Cameron & Foster 2009). A number of epidemiological studies have suggested that the dietary intake of phytoestrogens decreases the risk of breast cancer in humans (Badger et al 2005, Warri et al 2008, Wu et al 2008. Soy consumption during childhood and adolescence has been consistently linked to a marked reduction in breast cancer risk in Asian and AmericanAsians (Korde et al 2009), in agreement with some experimental studies showing that pubertal exposure to genistein (G), a natural phytoestrogen that is prevalent in plants (Wang et al 2006), reduces mammary cancer risk in rodent models (Warri et al 2008).…”

Section: Introductionsupporting

confidence: 53%

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Saad

Toullec

Vacher

et al. 2012

Journal of Endocrinology

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Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

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Section: Introductionsupporting

confidence: 53%

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Saad

Toullec

Vacher

et al. 2012

Journal of Endocrinology

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“…Human epidemiological data and in vitro animal studies suggest that genistein may possess breast cancer preventive properties (review by Warri et al, 2008) by altering expression of BRACA1 and PTEN and perhaps by epigenetic mechanisms. Similarly, in vitro data support an effect on mammary tumorogenesis, as exposure of human mammary cells to genistein altered the expression of certain cancer-related genes (Moon et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Feeding management of gilts during the early phase of mammary cell accretion (from 90 days of age until puberty; Sorensen et al, 2002) has an impact on mammary development (Farmer et al, 2004;Sorensen et al, 2006), and it is likely that specific feed ingredients may be useful in stimulating this process of mammogenesis. Phytoestrogens have gained increasing interest in recent years because of their potential health benefits in prevention of mammary cancer (review by Warri et al, 2008) and other benefits such as alleviation of bone loss in postmenopausal women -E-mail:Chantal.Farmer@agr.gc.ca (review by Lister et al, 2007). These naturally occurring plant compounds with estrogenic or anti-estrogenic activities (depending on the concentration of endogenous estrogens present; Sun Hwang et al, 2006) comprise three major classes.…”

Section: Introductionmentioning

confidence: 99%

Dietary genistein stimulates mammary hyperplasia in gilts

Farmer

Palin

Gilani

et al. 2010

Animal

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The possible role of the phytoestrogen genistein on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n 5 15), a control diet without soya (CTL0, n 5 15) or the CTLS diet supplemented with 2.3 g of genistein daily (GEN, n 5 15) from 90 days of age until slaughter (day 183 6 1). Both basal diets were isonitrogenous and isocaloric. Jugular blood samples were obtained on days 89 and 176 to determine concentrations of isoflavone metabolites (on day 176 only), prolactin, estradiol, progesterone, insulin-like growth factor 1 (IGF1), and N-telopeptide of type I collagen (NTx; on day 176 only). At slaughter, mammary glands were excised, parenchymal and extraparenchymal tissues were dissected, and composition of parenchymal tissue (protein, fat, dry matter (DM), DNA) was determined. Histochemical analyses of mammary parenchyma were performed. Dietary genistein increased parenchymal protein (P , 0.05) while decreasing DM (P , 0.05) and tending to lower fat content compared with the CTLS, but not the CTL0, diet. There was more parenchymal DNA (1.26 v. 0.92 mg/g, P , 0.05) in GEN than CTLS gilts, likely reflecting an increase in the quantity of mammary epithelial cells. Circulating concentrations of genistein were increased in GEN gilts (P , 0.001) but concentrations of hormones or NTx (indicator of bone collagen resorption) were not affected by GEN (P . 0.1). Percentage of estradiol receptor alpha (ERa)-positive epithelial cells was lower (P , 0.05) in GEN than CTLS gilts, whereas 5-bromo-2 0 -deoxyuridine labeling index was unaltered (P . 0.1). Transcript levels for ERa, ERb, IGF1, epidermal growth factor (EGF), epidermal growth factor receptor and transforming growth factor alpha were not altered by treatments. Supplementation of the diet with genistein during the growing phase in gilts, therefore, led to hyperplasia of mammary parenchymal tissue after puberty; yet, even though circulating genistein was increased, this was not accompanied by changes in mammary expression of selected genes or circulating hormone levels.

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“…They have gained much interest in recent years because of their potential health benefits in prevention of mammary cancer (review by Warri et al, 2008) and alleviation of bone loss in post-menopausal women (review by Lister et al, 2007). Phytoestrogens comprise three major classes, namely, isoflavones (including genistein), lignans and coumestans.…”

Section: Introductionmentioning

confidence: 99%

Effects of dose and route of administration of genistein on isoflavone concentrations in post-weaned and gestating sows

Farmer

Robertson

Gilani

2013

Animal

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Phytoestrogens could be a useful tool in swine husbandry practices because of their structural and functional similarities to estradiol. The goal of this study was to compare various routes and doses of administration of the phytoestrogen genistein in sows of two different physiological statuses. Circulating concentrations of isoflavones, estradiol and IGF-I were determined. In experiment 1, 65 sows were equally divided into the five following groups, between days 3 and 5 of the first or second estrous cycle post weaning: (1) controls (CTL); (2) 1 g of genistein fed daily (OR1); (3) 2 g of genistein fed daily (OR2); (4) two daily i.m. injections of 200 mg of genistein (IM400); and (5) two daily i.m. injections of 400 mg of genistein (IM800). Treatments were carried out for 10 days. In experiment 2, 10 sows were equally divided into two groups on day 90 of gestation, namely, controls (CTL) or 2 g of genistein fed daily for 10 days (OR2). In both trials, jugular blood samples were collected on days 1 (before treatment), 5 and 10 at 0730 h. In experiment 1, a blood sample was also collected at 1730 h on day 10 for CTL, IM400 and IM800 sows. In experiment 1, circulating concentrations of genistein on days 5 and 10 were greater in OR2, IM400 and IM800 than in CTL and OR1 group sows (P < 0.01). Daily dietary supplementation with 2 g of genistein resulted in blood concentrations that were similar to those in animals given daily two i.m. injections of 200 mg. Values of all isoflavones, except equol, which was not detectable, were greater in PM than in AM on day 10 (P < 0.01). In experiment 2, genistein concentrations were greater in OR2 compared with CTL on days 5 and 10 (P ⩽ 0.05). There was no difference in the genistein response to OR2 because of physiological status (i.e. weaned v. gestating, P > 0.1). Estradiol and IGF-I concentrations were not altered by any of the treatments (P > 0.1). Providing genistein either per os or via i.m. injections increased circulating concentrations of genistein in female swine within 5 days of the onset of treatment. The genistein response to i.m. injections of genistein was similar in weaned and late-pregnant sows, even though endogenous concentrations of estradiol differed. This response was specific in that estradiol, IGF-I and isoflavones other than genistein were not affected by treatments.

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The role of early life genistein exposures in modifying breast cancer risk

Cited by 132 publications

References 51 publications

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Dietary genistein stimulates mammary hyperplasia in gilts

Effects of dose and route of administration of genistein on isoflavone concentrations in post-weaned and gestating sows

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