The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.

Padilla-Banks, Elizabeth; Jefferson, Wendy N.; Newbold, Retha R.

doi:10.1289/ehp.01109821

Cited by 60 publications

(23 citation statements)

References 31 publications

(37 reference statements)

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“…Both mouse strains displayed a monotonic dose–response curve regarding uterine weight at the doses tested, and their response was comparable when uterine weight was normalized to body weight. Similar dose–response curves were reported in a 3-day (Padilla-Banks et al 2001) and a 10-day mouse assay (Skarda 2002). …”

Section: Discussionsupporting

confidence: 78%

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Perinatal Bisphenol A Exposure Increases Estrogen Sensitivity of the Mammary Gland in Diverse Mouse Strains

Wadia

Vandenberg

Schaeberle

et al. 2007

Environ Health Perspect

107

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BackgroundStudies of low-dose effects of xenoestrogens have yielded conflicting results that may be attributed to differences in estrogen sensitivity between the rodent strains examined. Perinatal exposure of CD-1 mice to low doses of the xenoestrogen bisphenol A (BPA) alters peripubertal mammary gland development. Future studies to assess the role of estrogen receptors as mediators of BPA action require estrogen receptor knock-out mice that were generated on a C57Bl6 background. The sensitivity of the C57Bl6 strain to estradiol and BPA is unknown.ObjectivesIn the present study we examined whether the mammary glands of CD-1 and C57Bl6 mice exhibited similar responses to 17β-estradiol (E2) and whether perinatal exposure to BPA equally enhanced sensitivity of the mammary glands to E2 at puberty.MethodsImmature mice were ovariectomized and treated for 10 days with one of eight doses of E2. Morphological mammary gland parameters were examined to identify doses producing half-maximal effects. Mice were exposed perinatally to 0 or 250 ng BPA/kg body weight (bw)/day from gestational day 8 until postnatal day (PND) 2. On PND25, female offspring were ovariectomized and given an estrogen challenge of 0, 0.5, or 1 μg E2/kg bw/day for 10 days. Morphometric parameters of the mammary gland were compared between strains.ResultsBoth strains exhibited similar responses to E2. Perinatal BPA exposure altered responses to E2 at puberty for several parameters in both strains, although the effect in CD-1 was slightly more pronounced.ConclusionBoth mouse strains provide adequate models for the study of perinatal exposure to xenoestrogens.

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Section: Discussionsupporting

confidence: 78%

“…The mice were killed on PND35, and their mammary glands and uteri were collected. For positive controls, we used the range of E 2 doses previously reported in a mouse mammary gland assay by Skarda (2002) and a mouse uterotrophic assay (Padilla-Banks et al 2001) based on the wet weight of the uterus (a standard for estrogen exposure).…”

Section: Methodsmentioning

confidence: 99%

Perinatal Bisphenol A Exposure Increases Estrogen Sensitivity of the Mammary Gland in Diverse Mouse Strains

Wadia

Vandenberg

Schaeberle

et al. 2007

Environ Health Perspect

107

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“…A risk factor associated with estrogen therapy or compounds exerting estrogen-like effects is the growth stimulation of reproductive tissue, especially uterus. Increased uterine weight is a classical estrogen effect mediated by ERa (33)(34)(35). At equol levels of 0.1 or 0.5 mg/d, no effect on uterine weight was observed in OVX mice (27), whereas weight was increased in mice receiving equol injections at 12 and 20 mg/kg body weight per day (14).…”

Section: Discussionmentioning

confidence: 99%

Supplemental Dietary Racemic Equol Has Modest Benefits to Bone but Has Mild Uterotropic Activity in Ovariectomized Rats , ,

Legette

Martin

Shahnazari

et al. 2009

The Journal of Nutrition

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Soy isoflavones and their metabolites, with estrogenic activity, have been considered candidates for reducing postmenopausal bone loss. In this study, we examined the effect of dietary equol, a bioactive metabolite of the soy isoflavone daidzein, on equol tissue distribution, bone parameters, and reproductive tissue activity using an adult ovariectomized (OVX) rat model. An 8-wk feeding study was conducted to compare 4 dietary treatments of equol (0, 50, 100, 200 mg/kg diet) in 6-mo-old OVX female Sprague-Dawley rats. A dose response increase in tissue equol concentrations was observed for serum, liver, kidney, and heart, and a plateau occurred at 100 mg equol/kg diet for intestine. In OVX rats receiving 200 mg equol/kg diet, femoral calcium concentration was greater than those receiving lower doses but was still less than SHAM (P < 0.05), and other bone measures were not improved. Tibia calcium concentrations were lower in OVX rats receiving 100 and 200 mg equol/kg diet compared with the OVX control rats. Trabecular bone mineral density of tibia was also lower in equol-fed OVX rats. At this dietary equol intake, uterine weight was higher (P < 0.05) than in other OVX groups but lower than the SHAM-operated intact rats. The 200 mg/kg diet dose of dietary equol significantly increased proliferative index in the uterine epithelium. Dietary equol had no stimulatory effect on mammary gland epithelium. We conclude that in OVX rats, a dietary equol dose that had modest effect on bone also exerts mild uterotropic effects.

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“…Increases in uterine weight and epithelial proliferation are classical estrogen effects mediated by ER␣, and this effect is used to measure estrogenicity of environmental estrogens [30][31][32]. Equol was initially reported to be bio- logically inactive [33], but in vitro experiments have shown that equol binds both ER␣ and ER␤ [6,16].…”

Section: Discussionmentioning

confidence: 99%

Estrogenicity of the Isoflavone Metabolite Equol on Reproductive and Non-Reproductive Organs in Mice1

Selvaraj

Zakroczymski

Naaz

et al. 2004

Biology of Reproduction

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Equol, a metabolite of the phytoestrogen daidzein, is present at significant levels in some humans who consume soy and in rodents fed soy-based diets. Equol is estrogenic in vitro, but there have been limited studies of its activity in vivo. We evaluated equol effects on reproductive and non-reproductive endpoints in mice. Ovariectomized age-matched (30-day-old) female C57BL/6 mice were fed phytoestrogen-free diets and given a racemic mixture of equol by daily injections (0, 4, 8, 12, or 20 mg [kg body weight](-1) day(-1)) or in the diet (0, 500, or 1,000 ppm) for 12 days. Mice were killed, and serum concentrations of total and aglycone equol were measured. Total serum equol concentrations ranged from 1.4 to 7.5 microM with increasing doses of injected equol, but uterine weight increased significantly only at 12 and 20 mg (kg body weight)(-1) day(-1). Dietary equol at 500 or 1,000 ppm produced total serum equol concentrations of 5.9 and 8.1 microM, respectively, comparable with those in rodents consuming certain high-soy chows; the proportion of equol present as the free aglycone was much lower with dietary administration than injections, which may be a factor in the greater biological effects induced by injections. Dietary equol did not significantly increase uterine weight. Increasing dietary and injected equol doses caused a dose-dependent increase in vaginal epithelial thickness. Uterine epithelial proliferation was increased by equol injections at 8-20 mg (kg body weight)(-1) day(-1) and 1,000 ppm dietary equol. Neither dietary nor injected equol decreased thymic or adipose weights. In conclusion, equol is a weak estrogen with modest effects on endpoints regulated by estrogen receptor alpha when present at serum levels seen in rodents fed soy-based diets, but quantities present in humans may not be sufficient to induce estrogenic effects, although additive effects of equol with other phytoestrogens may occur.

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The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.

Cited by 60 publications

References 31 publications

Perinatal Bisphenol A Exposure Increases Estrogen Sensitivity of the Mammary Gland in Diverse Mouse Strains

Perinatal Bisphenol A Exposure Increases Estrogen Sensitivity of the Mammary Gland in Diverse Mouse Strains

Supplemental Dietary Racemic Equol Has Modest Benefits to Bone but Has Mild Uterotropic Activity in Ovariectomized Rats , ,

Estrogenicity of the Isoflavone Metabolite Equol on Reproductive and Non-Reproductive Organs in Mice1

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