Dietary estrogens—A probable cause of infertility and liver disease in captive cheetahs

Setchell, Kenneth D.R.; Gosselin, Sylvie; Welsh, Mary-Beth B.; Johnston, J.O'Neal; Balistreri, William F.; Kramer, Lynn W.; Dresser, B. L.; Tarr, Melinda J.

doi:10.1016/0016-5085(87)91006-7

Cited by 316 publications

(153 citation statements)

References 36 publications

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“…Despite several key reports highlighting the potency of dietary phytoestrogens in a number of large domestic and captive animal species (Bennetts et al, 1946;Setchell et al, 1987a), manufacturers still formulate rodent diets with soy meal, and in some instances the incorporation can be quite high. The use of such diets by animal suppliers means that many animals will have been subjected to multigenerational exposure to phytoestrogens, which may reduce or enhance the sensitivity of the animal to an estrogen, influence phenotype, or modulate the sensitivity of a variety of genomic and non-genomic pathways.…”

Section: Discussionmentioning

confidence: 99%

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

Brown

Setchell

2001

Laboratory Investigation

273

239

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SUMMARY:It is generally not known that most commercial rodent diets are formulated with soy protein and deliver large daily doses of isoflavones to animals throughout their lifespan, including the in utero period. Here, we demonstrate that isoflavones are bioavailable and show that commercial rodent diets universally used by animal facilities lead to very high steady-state serum isoflavone concentrations in adult rats (2613 Ϯ 873 ng/mL) and mice (2338 Ϯ 531 ng/mL), exceeding the animal's endogenous estrogen level by 30,000-to 60,000-fold. We demonstrate the maternal-fetal intrauterine transfer of isoflavones in animals fed a standard Purina 5001 soy-containing diet and show that newborn rat pups have high serum isoflavones levels (540 Ϯ 174 ng/mL) that are maintained throughout the suckling period by passage of isoflavones into maternal milk. These findings have profound implications for all animal experiments, including multigenerational studies and studies of transgenic animals, especially if biochemical or morphological end-points are influenced by the hormonal or nonhormonal properties of phytoestrogens. These compounds have the potential to modulate genotypic and phenotypic expression in general, and therefore, all investigators should be vigilant to the phytoestrogen composition of commercial rodent diets because there is a history of potent biological effects in larger animals and in humans from high circulating isoflavone concentrations. (Lab Invest 2001, 81:735-747).A lthough phytoestrogens are ubiquitous in the plant kingdom, it is soybeans and foods made with purified soy proteins that are by far the greatest contributors of isoflavones to animal and human diets (Coward et

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Section: Discussionmentioning

confidence: 99%

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

Brown

Setchell

2001

Laboratory Investigation

273

239

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“…In wet years, these quails bred normally and phytoestrogens were largely absent in these herbs (Leopold et al, 1976). Finally in captured cheetahs, cases of infertility and liver disease were attributed to the consumption of a soy-based diet and the exposure to high levels of isoflavones ( 50 mg/day; Setchell et al, 1987).…”

Section: Soy and Phytoestrogens As Potential Sources Of Endocrinedisrmentioning

confidence: 99%

Soy, phytoestrogens and their impact on reproductive health

Cederroth

Zimmermann

Nef

2012

Molecular and Cellular Endocrinology

193

117

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a b s t r a c tThere is growing interest in the potential health threats posed by endocrine-disrupting chemicals (EDCs) to the reproductive system. Soybean is the most important dietary source of isoflavones, an important class of phytoestrogen. While consumption of soy food or phytoestrogen supplements has been frequently associated with beneficial health effects, the potentially adverse effects on development, fertility, and the reproductive and endocrine systems are likely underappreciated. Here we review the available epidemiological, clinical and animal data on the effects of soy and phytoestrogens on the development and function of the male and female reproductive system, and weigh the evidence as to their detrimental impact.

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“…Compromised follicular development (91) and reductions in luteal phase plasma progesterone and E 2 , as well as shortened luteal phases, have been reported in cycling ewes whereas increases in estradiol and cortisol have been reported in pregnant ewes (93,94). Soy isoflavone diets providing doses of 1 mg/kg/day were associated with infertility in captive cheetahs (95).…”

Section: Ovarian Cyclicitymentioning

confidence: 99%

Cross-species and interassay comparisons of phytoestrogen action.

Whitten

Patisaul

2001

Environ Health Perspect

174

105

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This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

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Dietary estrogens—A probable cause of infertility and liver disease in captive cheetahs

Cited by 316 publications

References 36 publications

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

Soy, phytoestrogens and their impact on reproductive health

Cross-species and interassay comparisons of phytoestrogen action.

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