Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but Not in CD Sprague-Dawley Rats

Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 01/2008; 115(12):1717-26. DOI: 10.1289/ehp.10165
Source: PubMed


The optimum test diet and rodent species/strain for evaluating endocrine-disrupting compounds (EDCs) are critical.
We conducted studies to evaluate rodent species sensitivity and the effects of diets varying in phytoestrogen content on the time of vaginal opening (VO) in CD-1 mice, Fischer 344 (F344) rats, and CD Sprague-Dawley (S-D) rats.
Mice were weaned on postnatal day (PND) 15 and rats on PND19 and randomly assigned to control or test diets. Body weights, food consumption, and time of VO were recorded.
The time of VO was significantly advanced in F344 rats fed diets containing daidzein and genistein, whereas these same diets did not advance VO in S-D rats. When animals were fed the AIN-76A diet spiked with genistein, time of VO was significantly advanced at all doses in CD-1 mice, at the two highest doses in F344 rats, and at the highest dose in S-D rats. The time of VO in F344 rats was more highly correlated with the phytoestrogen content than with the total metabolizable energy (ME) of 12 diets.
The S-D rat is less sensitive to dietary phytoestrogens compared with the F344 rat or the CD-1 mouse, suggesting that the S-D rat is not the ideal model for evaluating estrogenic activity of EDCs. The profound effects of dietary phytoestrogens on the time of VO, an estrogen-sensitive marker, indicate that a standardized open-formula phytoestrogen-free diet containing a low ME level should be used to optimize the sensitivity of estrogenic bioassays.

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Available from: Elizabeth Padilla-Banks, Oct 05, 2015
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    • "A1: There are noticeable interspecies differences in endocrine biology, for example, in the timing of critical windows of vulnerability to EASs/EDCs during development or in the hormones required to maintain pregnancy and similar interspecies differences in endocrine-mediated pathogenesis. It was reported that the same EAS/EDC exposure may result in different phenotype modifications according to the rodent species or strains.4748 Numerous differences in toxicokinetics are described from one species to another.49 "
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    Asian Journal of Andrology 01/2014; 16(1):60-70. DOI:10.4103/1008-682X.122366 · 2.60 Impact Factor
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    • "Additionally, vaginal opening was advanced in CD-1 mice fed a diet spiked with 150, 300, or 450 mg genistein/g food and in F344 rats fed the 300 and 450 mg genistein/g food diets (Thigpen et al., 2007). Each of these experiments was also performed with Sprague-Dawley rats, but no advance in vaginal opening was noted in this strain (Thigpen et al., 2007). Thus, these experiments highlight the necessity of choosing the appropriate animal species and strain for testing xenoestrogen-sensitive endpoints. "
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    ABSTRACT: The United States presently uses more than 80 000 chemicals, a number that is estimated to grow by 2000 chemicals each year. Although generally not considered toxic at current exposure levels, many of these chemicals interfere with the endocrine system and may have profound effects on reproduction. Exposure to endocrine-disrupting chemicals (EDCs) is associated with an earlier onset of puberty, decreased fecundity and fertility, altered sexual behavior, and increased incidence of abnormalities and cancers of the reproductive tract in humans and in laboratory animals. Importantly, it appears that developing organisms may be particularly sensitive to slight variations in the hormonal milieu that occurs after exposure to some chemicals. In this chapter we review the sources and mechanisms of several well-studied EDCs and the evidence that exposure to these chemicals affects many aspects of mammalian reproduction.
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    • "These differences in phytoestrogen effects in previous studies may be due, in part, to the different rat strains used in those studies. A recent report [66] showed that Sprague-Dawley rats were less sensitive to phytoestrogens than Fisher 344 rats or CD-1 mice in evaluations of estrogenic activity. To compare results from the present study with those found in previous experiments employing Noble rats, a computer-assisted literature search was conducted. "
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    Nutrition & Metabolism 12/2008; 5:31. DOI:10.1186/1743-7075-5-31 · 3.26 Impact Factor
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