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Cited by 102Phytoestrogen effects and researchEffects and risks of endocrine disrupting chemicalsEstrogen and related hormone effects

Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the “fetal estrogenization syndrome” and obesity in CD-1 mice.

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Ruhlen, Rachel L., Howdeshell, Kembra L., Mao, Jiude, Taylor, Julia A., Bronson, Franklin H., Newbold, Retha R., Welshons, Wade V., vom Saal, Frederick S.·2008·Environmental Health Perspectives
DOI 10.1289/ehp.10448PMC PMC2265041
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Abstract

Background: Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. Objectives: We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. Methods: The low-phytoestrogen diet was non-soy PMI 5K96 (verified casein diet), and the high-phytoestrogen diet consisted of soy-based PMI 5008 during pregnancy and lactation and soy-based PMI 5001 maintenance feed after weaning. Results: In fetuses whose mothers consumed the low-phytoestrogen PMI 5K96 feed, we found a paradoxical significant elevation in endogenous serum estradiol, which was associated postnatally with adverse reproductive outcomes referred to as the “fetal estrogenization syndrome (FES)”. In females, this syndrome included early puberty and increased uterine responsiveness to estrogen, and in males, it included reduced testis, epididymis, and seminal vesicle size, but an enlarged prostate. The low-phytoestrogen–fed males and females were lighter at birth, but, between weaning and adulthood, they became obese and developed abnormally high serum leptin levels; these males, but not females, showed impaired glucose regulation. Conclusions: Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research.

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  • Phytoestrogens in chow can enhance sex differences in the brain and in behavior.

    “Phytoestrogens in chow can enhance sex differences in the brain and in behavior [51], [52], [53], [54], [55].”

    From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [51]

    The Objectives and Results compare reproductive and metabolic outcomes in male and female mice on different feeds, but do not report sex differences in the brain or behavior. Searches for brain, behavior, and sexual dimorphism found no passage supporting the attributed claim. (LLM, conf=0.72)

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Research works printed but not linked: 36

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Authors
Ruhlen, R. L., Howdeshell, K. L., Mao, J., Taylor, J. A., Bronson, F. H., Newbold, R. R., Welshons, W. V., & vom Saal, F. S.
Affiliations
  • University of Missouri (US)
  • The University of Texas at Austin (US)
  • National Institutes of Health (US)
  • Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri, USA
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2007-11-26
Volume
116
Issue
3
Pages
322-328
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp.10448
PMC
PMC2265041
OpenAlex
W2081491312
Cited by
102
References
3
Citations by year
2024: 2 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 10 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 9 · 2012: 8
FWCI
5.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • MOspace Institutional Repository (University of Missouri) (submittedVersion)
Funders
  • U.S. Environmental Protection Agency
  • National Institutes of Health
  • National Institute of General Medical Sciences (T32GM008396)
  • National Institute of Environmental Health Sciences (ES-11283, R01ES011283)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
phytoestrogens, reproductive toxicity, obesity, metabolic syndrome, leptin, glucose regulation, puberty, male reproductive tract, prostate enlargement, ICR mice, developmental origins of health and disease
MeSH terms
Animals, Animal Feed, Animals, Newborn, Birth Weight, Estradiol, Female, Genitalia, Female, Genitalia, Male, Glucose Tolerance Test, Humans, Male, Maternal-Fetal Exchange, Obesity, Pregnancy, Maternal Exposure, Leptin, Cell Line, Tumor, Phytoestrogens, Mice

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