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ToxSci Advance Access originally published online on June 14, 2007
Toxicological Sciences 2007 99(1):244-253; doi:10.1093/toxsci/kfm162
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Arsenic Exposure in Pregnant Mice Disrupts Placental Vasculogenesis and Causes Spontaneous Abortion

Wenjie He, Robert J. Greenwell, Diane M. Brooks, Lilian Calderón-Garcidueñas, Howard D. Beall and J. Douglas Coffin1

Department of Biomedical and Pharmaceutical Sciences and Center for Environmental Health Sciences, The University of Montana, Missoula, Montana 59812

1 To whom correspondence should be addressed at The University of Montana, Department of Biomedical and Pharmaceutical Sciences, SB 160, Missoula, MT 59812-1552. Fax: (406) 243-5228. E-mail: douglas.coffin{at}umontana.edu.

Received April 21, 2007; accepted June 11, 2007


  Abstract

Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency.

Key Words: arsenic; vasculogenesis; placenta; development; mouse.


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