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Drinking water with uranium below the U.S. EPA water standard causes estrogen receptor-dependent responses in female mice

Raymond-Whish, Stefanie and Mayer, Loretta P. and O'Neal, Tamara and Martinez, Alisyn and Sellers, Marilee A. and Christian, Patricia J. and Marion, Samuel L. and Begay, Carlyle and Propper, Catherine R and Hoyer, Patricia B. and Dyer, Cheryl A. (2007) Drinking water with uranium below the U.S. EPA water standard causes estrogen receptor-dependent responses in female mice. Environmental Health Perspectives, 115 (12). pp. 1711-1716. ISSN 1552-9924


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Publisher’s or external URL: http://dx.doi.org/10.1289/ehp.9910


Background: The deleterious impact of uranium on human health has been linked to its radioactive and heavy metal-chemical properties. Decades of research has defined the causal relationship between uranium mining/milling and onset of kidney and respiratory diseases 25 years later. Objective: We investigated the hypothesis that uranium, similar to other heavy metals such as cadmium, acts like estrogen. Methods: In several experiments, we exposed intact, ovariectomized, or pregnant mice to depleted uranium in drinking water [ranging from 0.5 μg/L (0.001 μM) to 28 mg/L (120 μM). Results: Mice that drank uranium-containing water exhibited estrogenic responses including selective reduction of primary follicles, increased uterine weight, greater uterine luminal epithelial cell height, accelerated vaginal opening, and persistent presence of cornified vaginal cells. Coincident treatment with the antiestrogen ICI 182,780 blocked these responses to uranium or the synthetic estrogen diethylstilbestrol. In addition, mouse dams that drank uranium-containing water delivered grossly normal pups, but they had significantly fewer primordial follicles than pups whose dams drank control tap water. Conclusions: Because of the decades of uranium mining/milling in the Colorado plateau in the Four Corners region of the American Southwest, the uranium concentration and the route of exposure used in these studies are environmentally relevant. Our data support the conclusion that uranium is an endocrine-disrupting chemical and populations exposed to environmental uranium should be followed for increased risk of fertility problems and reproductive cancers.

Item Type: Article
Publisher’s Statement: Reproduced with permission from Environmental Health Perspectives
ID number or DOI: 10.1289/ehp.9910
Keywords: alpha; Animals; Antiestrogens; bisphenol-a; Body weight; breast-cancer cells; cadmium; Cancer; chemicals; Dams; Depleted uranium; Diethylstilbestrol; Diseases -- Causes & theories of causation; Drinking water; Endocrine disruption; Endocrine disruptors; Epithelial cells; Estrogen; estrogen receptor; Estrogen receptors; Estrogens; Female; female reproduction; Fertility; Follicles; Four Corners Region -- Environmental conditions; Genitalia, Female; Heavy metal; heavy metals; in-vitro; Kidney; kidney diseases; Kidneys; Maternal Exposure; mice; Mice as laboratory animals; Mice, Inbred C57BL; mining; Mouse; Navajo reservation; Organ Size; Ovarian follicle; Ovariectomy; Physiological aspects; Physiology; Pregnancy; Proliferation; Receptors, Estrogen; research; Respiratory diseases; Southwestern States -- Environmental conditions; Standards; United States; United States Environmental Protection Agency; Uranium; Uranium -- Environmental aspects; uterotrophic bioassay; Uterus; Vagina; Water Pollutants, Radioactive; Water Pollution Effects; Water supply
Subjects: R Medicine > RA Public aspects of medicine
NAU Depositing Author Academic Status: Faculty/Staff
Department/Unit: College of Engineering, Forestry, and Natural Science > Biological Sciences
Date Deposited: 30 Sep 2015 18:39
URI: http://openknowledge.nau.edu/id/eprint/579

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