The development of methods for assessing the in vivo oestrogen-like effects of xenobiotics in CD-1 mice

Mehmood, Z.; Smith, Andrew G.; Tucker, Mary J.; Chuzel, Franck; Carmichael, Neil G.

doi:10.1016/s0278-6915(00)00022-3

Cited by 59 publications

(27 citation statements)

References 33 publications

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“…For example, effects on uterine weight have been observed at relatively high doses of BPA (25 to 40 mg/kg/day), while changes in uterine gene activity occurred at lower doses of 10 mg/kg/day in B6C3F1 mice and 0.8 mg/kg in transgenic ERIN mice [173][174][175]. In prepubertal CD-1 mice, a dose of 100 mg/kg/day injected s.c. for 3 days was required to stimulate an increase in uterine weight [176]; however, 5 mg/kg/day was sufficient to cause a significant increase in the height of uterine epithelial cells in this strain, Similar findings regarding the inability of low doses of BPA to stimulate a uterotrophic response in prepubertal CD-1 mice were reported in another study [177], which, in comparison to the B6C3F1 mouse data, provides further evidence for strain differences in sensitivity to BPA.…”

Section: Bpa As a Serm: Responses In Different Tissues And In Differesupporting

confidence: 83%

In vivo effects of bisphenol A in laboratory rodent studies

Richter

Birnbaum

Farabollini

et al. 2007

Reproductive Toxicology

1,028

733

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Concern is mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical used in synthesis of plastics. We have reviewed the growing literature on effects of low doses of BPA, below 50 mg/kg/day, in laboratory exposures with mammalian model organisms. Many, but not all, effects of BPA are similar to effects seen in response to the model estrogens diethylstilbestrol and ethinylestradiol. For most effects, the potency of BPA is approximately 10 to 1,000-fold less than that of diethylstilbestrol or ethinylestradiol. Based on our review of the literature, a consensus was reached regarding our level of confidence that particular outcomes occur in response to low-dose BPA exposure. We are confident that adult exposure to BPA affects the male reproductive tract, and that long-lasting, organizational effects in response to developmental exposure to BPA occur in the brain, the male reproductive system, and metabolic processes. We consider it likely, but requiring further confirmation, that adult exposure to BPA affects the brain, the female reproductive system, and the immune system, and that developmental effects occur in the female reproductive system.

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Section: Bpa As a Serm: Responses In Different Tissues And In Differesupporting

confidence: 83%

In vivo effects of bisphenol A in laboratory rodent studies

Richter

Birnbaum

Farabollini

et al. 2007

Reproductive Toxicology

1,028

733

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“…Since IL-4 helps differentiation and proliferation of Th2 cells, BPA activates synergistically the Th2 subset. No consistent histological and biochemical changes in reproductive organs were reported in male and female adult mice inoculated with BPA at the doses comparable to those reported in this paper [32, 33]. This implies that these chemicals affect the immune system more sensitively than the reproductive systems.…”

Section: Discussionsupporting

confidence: 49%

Bisphenol A Promotes IL-4 Production by Th2 Cells

Tian

Takamoto

Sugane

2003

Int Arch Allergy Immunol

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Background: It has been proposed that estrogen plays an important role in modulating the Th1/Th2 cytokine balance. From this viewpoint, chemicals with estrogenic responses were expected to possess similar immunoregulatory roles which have not been defined to date. To address this, we studied the effects of one of the estrogenic chemicals, bisphenol A (BPA), on the in vitro production of Th1 and Th2 cytokines. Methods: Mesenteric lymph node cells from Trichinella spiralis (Ts)-infected mice were incubated with serialfold dilutions of BPA under stimulation with Ts antigen. The Th2 cytokine production in the supernatant was determined by ELISA. The Th2 cytokine production by mesenteric lymph node cells from Ts-infected mice inoculated orally with BPA was compared with that of uninoculated mice infected with Ts. Results: The antigen-stimulated interleukin (IL)-4 production by Th2-dominant mesenteric lymph node cells from Ts-infected mice increased significantly by addition of 3 µM of BPA. The IL-5 production was not affected. The production of IL-4, but not that of IL-5, by splenocytes of Th2-skewed Leishmania major-infected BALB/c mice increased at concentrations of 3 and 10 µM of BPA. However, the interferon gamma production was not affected by BPA in Th1-skewed L. major-infected C57BL/6 mice. The production of IL-4 and IL-10, but not that of IL-13, markedly increased in Ts-infected mice inoculated orally with BPA. Conclusions: We demonstrated that the IL-4 production was increased both in vitro and in vivo by treatment with BPA. This suggests that BPA might cause allergic diseases by stimulating the IL-4 production by Th2 cells.

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“…MXC, at 100 mg/kg/day, increased uterine wet weight and epithelial height to about one-third that of E 2 2 µg/kg/day. These findings resemble those of Laws et al (2000) and Mehmood et al (2000), whose study designs were similar to the one employed in the present study. In addition, MXC significantly increased levels of hsp90α and grp94.…”

Section: Discussionsupporting

confidence: 86%

“…Increases in uterine weight have been reported for CM (Hunter et al 1999;Markaverich et al 1995;Tinwell et al 2000), MXC (Eroshenko and Cooke 1990;Laws et al 2000;Mehmood et al 2000), and BPA (Ashby and Tinwell 1998;Laws et al 2000;Papaconstantinou et al 2000). Increases in uterine epithelial cell height have been shown for CM (Medlock et al 1995;O'Connor et al 2000), for MXC (Eroshenko and Cooke 1990;Newbold et al 2001;Rourke et al 1991), and for BPA (Markey et al 2001;Papaconstantinou et al 2000;Steinmetz et al 1998).…”

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confidence: 95%

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Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

Papaconstantinou

Fisher

Umbreit

et al. 2002

Environ Health Perspect

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There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown that bisphenol A (BPA), similarly to 17ss-estradiol (E2), increases levels of uterine heat shock proteins (hsps), mainly hsp90alpha and glucose-regulated protein (grp) 94. In this study we investigated whether increases in uterine hsp levels are a specific response of estrogens or estrogen mimics. We therefore examined the ability of a) E2, diethylstilbestrol (DES), and tamoxifen (TAM); b) the xenoestrogens coumestrol (CM), methoxychlor (MXC), BPA, and dibutyl phthalate (DBP); c) the progestin medroxyprogesterone (MED); d) the glucocorticoid dexamethasone (DEX); and e) phytol (PHY), a precursor to a retinoid X and peroxisome proliferator-activating receptor agonist, to increase uterine weights and alter uterine morphology and hsp levels. We showed that DES, TAM, CM, MXC, and BPA significantly increased uterine weights and uterine hsp90alpha and grp94 levels. Even though the doses of CM, MXC, and BPA used were much higher than the E2 dose, those treatments resulted in lower increases in uterine weight. On the other hand, increases in grp94 levels were equal to those induced by E2 treatment. Treatments with MED, DEX, DBP, or PHY did not significantly alter uterine weight or morphology and had no significant effects on uterine hsp levels. The results of this study suggest that only the estrogens increase uterine hsp90alpha and grp94 levels, and that this hsp effect is a more sensitive uterotrophic response than uterine weight increase.

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The development of methods for assessing the in vivo oestrogen-like effects of xenobiotics in CD-1 mice

Cited by 59 publications

References 33 publications

In vivo effects of bisphenol A in laboratory rodent studies

In vivo effects of bisphenol A in laboratory rodent studies

Bisphenol A Promotes IL-4 Production by Th2 Cells

Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

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