| 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 Julius E. Thigpen,1 Kenneth D.R. Setchell,2,3 Elizabeth Padilla-Banks,1 Joseph K. Haseman,4 Hannah E. Saunders,1 Gordon F. Caviness,1 Grace E. Kissling,4 Mary G. Grant,1 and Diane B. Forsythe1 1Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA; 2Department of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; 3Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; 4Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Abstract
Background: The optimum test diet and rodent species/strain for evaluating endocrine-disrupting compounds (EDCs) are critical. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Key words: dietary phytoestrogens, endocrine disruptors, rodent species/strain sensitivities in VO end points. Environ Health Perspect 115:1717–1726 (2007) . doi:10.1289/ehp.10165 available via http://dx.doi.org/ [Online 21 September 2007]
Address correspondence to J.E. Thigpen, Quality Assurance Laboratory, Comparative Medicine Branch, National Institute of Environmental Health Sciences, P.O.Box 12233, Mail Drop C1-06, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-3239. Fax: (919) 316-4554. E-mail: thigpen@niehs.nih.gov We thank P. Deese, M. Fender, and B. Collins for their assistance with reviewing/editing the manuscript ; R. Tice, W. Stokes, and J. Roberts for their review of the manuscript ; and J. Locklear, T. Whiteside, L. Eckerd, S. Joshi, S. Little, A. Helmich, L. Zimmer-Nechemias, and B. Wolfe for technical support. The authors declare they have no competing financial interests. Received 13 February 2007 ; accepted 21 September 2007.
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