Drinking water with uranium below the U.S. EPA water standard causes estrogen receptor-dependent responses in female mice.
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 microg/L (0.001 microM) to 28 mg/L (120 microM).


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.
Raymond-Whish
Stefanie
S
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA.
Mayer
Loretta P
LP
O'Neal
Tamara
T
Martinez
Alisyn
A
Sellers
Marilee A
MA
Christian
Patricia J
PJ
Marion
Samuel L
SL
Begay
Carlyle
C
Propper
Catherine R
CR
Hoyer
Patricia B
PB
Dyer
Cheryl A
CA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005836:Genitalia, Female / Q000166:cytology / Q000187:drug effects; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects; D010052:Ovariectomy; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000378:metabolism*; D014481:United States; D014484:United States Environmental Protection Agency; D014501:Uranium / Q000633:toxicity*; D014875:Water Pollutants, Radioactive / Q000633:toxicity*; D014881:Water Supply / Q000592:standards*
D011960:Receptors, Estrogen; D014875:Water Pollutants, Radioactive; D014501:Uranium; D004054:Diethylstilbestrol