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Choice of animal feed can alter fetal steroid levels and mask developmental effects of endocrine disrupting chemicals

Published online by Cambridge University Press:  28 January 2011

R. L. Ruhlen ,
J. A. Taylor ,
J. Mao ,
J. Kirkpatrick ,
W. V. Welshons  and
F. S. vom Saal
R. L. Ruhlen*
Affiliation:
Division of Biological Sciences, University of Missouri, Columbia, MO, USA
J. A. Taylor
Affiliation:
Division of Biological Sciences, University of Missouri, Columbia, MO, USA
J. Mao
Affiliation:
Division of Biological Sciences, University of Missouri, Columbia, MO, USA
J. Kirkpatrick
Affiliation:
Division of Biological Sciences, University of Missouri, Columbia, MO, USA
W. V. Welshons
Affiliation:
Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA
F. S. vom Saal
Affiliation:
Division of Biological Sciences, University of Missouri, Columbia, MO, USA
*
*Address for correspondence: R. L. Ruhlen, A.T. Still Research Institute, A.T. Still University, 800 W. Jefferson Street, Kirksville, MO 63501, USA. (Email [email protected])
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Abstract

Exposure of fetuses to endocrine disrupting chemicals (EDCs), such as the estrogenic drug diethylstilbestrol (DES), disrupts development of the reproductive system and affects other aspects of adult phenotype including diseases, consistent with the developmental origins of health and disease hypothesis. To determine whether diet could influence the effects of DES, we compared mice fed a commonly used combination of soy-based Purina 5008 (breeding and lactation) and 5001 (post-weaning) with mice fed soy-based Purina 5002 throughout life. We exposed fetal CD-1 mice (F1) in utero on different feeds to a 0 (controls), low (0.1 μg/kg/day) or high (50 μg/kg/day) dose of DES via feeding the dam (F0) on gestation days 11–17. Compared to 5008, 5002 feed significantly increased serum estradiol in control fetuses. On 5008 (but not 5002) feed, DES significantly increased fetal serum estradiol at a low dose and reduced it at a high dose. Diet influenced the effects of in utero DES on F1 female onset of puberty and the uterine response to estradiol (an inverted-U dose–response relationship seen for DES on uterine weight with 5008/5001 feed was not observed with 5002). Both low- and high-dose DES reduced daily sperm production (DSP) in adult F1 males on 5008/5001 feed, whereas males fed 5002 showed no DES-induced reduction in DSP. Thus, we observed a number of low-dose effects of in utero DES exposure on Purina 5008/5001 feed that were not observed using Purina 5002, a feed commonly used in industry-funded toxicological studies conducted for regulatory purposes.

Keywords

dietendocrine disruptorsfertilitymouse modelphytoestrogens
Type
Themed Content: Role of Environmental Stressors in the Developmental Origins of Disease
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 1: Including Themed Content: Role of Environmental Stressors in the Developmental Origins of Disease , 23 February 2011 , pp. 36 - 48
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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References

1.Heindel, JJ, vom Saal, FS. Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets – importance and approaches for laboratory animal research. Environ Health Perspect. 2008; 116, 389–393.CrossRefGoogle ScholarPubMed
2.Barnard, DE, Lewis, SM, Teter, BB, Thigpen, JE. Open- and closed-formula laboratory animal diets and their importance to research. J Am Assoc Lab Anim Sci. 2009; 48, 709–713.Google ScholarPubMed
3.Thigpen, JE, Setchell, KD, Padilla-Banks, E, et al. 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. Environ Health Perspect. 2007; 115, 1717–1726.CrossRefGoogle ScholarPubMed
4.Boettger-Tong, H, Murthy, L, Chiappetta, C, et al. A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens. Environ Health Perspect. 1998; 106, 369–373.CrossRefGoogle ScholarPubMed
5.Thigpen, JE, Haseman, JK, Saunders, HE, et al. Dietary phytoestrogens accelerate the time of vaginal opening in immature CD-1 mice. Comp Med. 2003; 53, 607–615.Google Scholar
6.Cederroth, CR, Vinciguerra, M, Kuhne, F, et al. A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice. Environ Health Perspect. 2007; 115, 1467–1473.CrossRefGoogle ScholarPubMed
7.Ruhlen, RL, Howdeshell, KL, Mao, J, et al. Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the ‘fetal estrogenization syndrome’ and obesity in CD-1 mice. Environ Health Perspect. 2008; 116, 322–328.CrossRefGoogle ScholarPubMed
8.vom Saal, FS, Timms, BG, Montano, MM, et al. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci. 1997; 94, 2056–2061.Google Scholar
9. NTP. NTP 2001 Endocrine Disruptors Low Dose Peer review, final report; http://ntp.niehs.nih.gov/ntp/htdocs/liason/LowDosePeerFinalRpt.pdf (accessed 3 January 2011).Google Scholar
10.Cagen, SZ, Waechter, JM, Dimond, SS, et al. Normal reproductive organ development in CF-1 mice following prenatal exposure to Bisphenol A. Toxicol Sci. 1999; 11, 15–29.Google Scholar
11.Tyl, R, Myers, C, Marr, M, et al. Three-generation reproductive toxicity study of dietary bisphenol A in CD Sprague–Dawley rats. Toxicol Sci. 2002; 68, 121–146.CrossRefGoogle ScholarPubMed
12.Tyl, RW, Myers, C, Marr, M, et al. Two-generation reproductive toxicity study of dietary bisphenol A (BPA) in CD-1® (Swiss) mice. Toxicol Sci. 2008; 102, 362–384.Google Scholar
13.Stump, DG, Beck, MJ, Radovsky, A, et al. Developmental neurotoxicity study of dietary bisphenol A in Sprague–Dawley rats. Toxicol Sci. 2010; 115, 167–182.Google Scholar
14.vom Saal, FS, Hughes, C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect. 2005; 113, 926–933.CrossRefGoogle ScholarPubMed
15.Richter, CA, Birnbaum, LS, Farabollini, F, et al. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol. 2007; 24, 199–224.Google Scholar
16.Myers, JP, vom Saal, FS, Akingbemi, BT, et al. Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: the case of bisphenol A. Environ Health Perspect. 2009; 117, 309–315.Google Scholar
17.vom Saal, FS, Welshons, WV. Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A. Environ Res. 2006; 100, 50–76.Google Scholar
18.Howdeshell, KL, Peterman, PH, Judy, BM, et al. Bisphenol A is released from used polycarbonate animal cages into water at room temperature. Environ Health Perspect. 2003; 111, 1180–1187.Google Scholar
19.vom Saal, FS, Quadagno, DM, Even, MD, et al. Paradoxical effects of maternal stress on fetal steroid and postnatal reproductive traits in female mice from different intrauterine positions. Biol Reprod. 1990; 43, 751–761.Google Scholar
20.Grady, LH, Nonneman, DJ, Rottinghaus, GE, Welshons, WV. pH-Dependent cytotoxicity of contaminants of phenol red for MCF-7 breast cancer cells. Endocrinology. 1991; 129, 3321–3330.CrossRefGoogle ScholarPubMed
21.Alworth, LC, Howdeshell, KL, Ruhlen, RL, et al. Imprinting of uterine response to estradiol and ribosomal gene methylation due to fetal exposure to diethylstilbestrol and methoxychlor in CD-1 mice: opposite effects of low and high doses. Tox Appl Pharm. 2002; 183, 10–22.CrossRefGoogle Scholar
22.Myers, JP, Zoeller, TJ, vom Saal, FS. A clash of old and new scientific concepts in toxicity, with important implications for public health. Environ Health Perspect. 2009; 117, 1652–1655.Google Scholar
23.Thigpen, JE, Setchell, KD, Saunders, HE, et al. Selecting the appropriate rodent diet for endocrine disruptor research and testing studies. ILAR J. 2004; 45, 401–416.CrossRefGoogle ScholarPubMed
24.Thayer, KA, Ruhlen, RL, Howdeshell, KL, et al. Altered reproductive organs in male mice exposed prenatally to sub-clinical doses of 17a-ethinyl estradiol. Hum Reprod. 2001; 16, 988–996.Google Scholar
25.Weiss, B, Stern, S, Cernichiari, E, Gelein, R. Methylmercury contamination of laboratory animal diets. Environ Health Perspect. 2005; 113, 1120–1122.CrossRefGoogle ScholarPubMed
26. Environment Working Group. First-ever U.S. tests of farmed salmon show high levels of cancer-causing PCBs. 2003; http://www.ewg.org/release/first-ever-us-tests-farmed-salmon-show-high-levels-cancer-causing-pcbs (accessed 3 January 2011).Google Scholar
27.Thigpen, JE, Haseman, JK, Saunders, HE, et al. Dietary phytoestrogens accelerate the time of vaginal opening in immature CD-1 mice. Comp Med. 2003; 53, 477–485.Google ScholarPubMed
28.Ryan, KK, Haller, AM, Sorrell, JE, et al. Perinatal exposure to bisphenol-a and the development of metabolic syndrome in CD-1 mice. Endocrinology. 2010; 151, 2603–2612.Google Scholar
29.vom Saal, FS, Welshons, WV. Bisphenol A and the development of metabolic syndrome in mice. Endocrinology. 2010, E-pub 20 July 2010; http://endo.endojournals.org/cgi/eletters/151/6/2603Google Scholar
30. NTP. NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A. In: National Toxicology Program, NIH Publication no. 08-5994.2008; http://oehha.ca.gov/prop65/CRNR_notices/state_listing/data_callin/pdf/NTP_CERHR_0908_bisphenolA.pdf (accessed 3 January 2011).Google Scholar
31.Thigpen, JE, Setchell, KDR, Goelz, MF, Forsythe, DB. The phytoestrogen content of rodent diets. Environ Health Perspect. 1999; 107, A182–A183.Google Scholar