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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 rruhlen@atsu.edu)
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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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