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ToxSci Advance Access published online on September 11, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg225
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received June 5, 2003; accepted August 14, 2003
© 2003 Society of Toxicology

Endocrine Toxicology

Effect of Bromodichloromethane on Chorionic Gonadotrophin Secretion by Human Placental Trophoblast Cultures

Jiangang Chen 1, Gordon C. Douglas 2, Twanda L. Thirkill 2, Peter N. Lohstroh 1, Susan R. Bielmeier 3, Michael G. Narotsky 4, Deborah S. Best 4, Randy A. Harrison 5, Kala Natarajan 1, Rex A. Pegram 5, James W. Overstreet 1, and Bill L. Lasley 1*

1 Center for Health and the Environment, School of Medicine, University of California, Davis, CA 95616
2 Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA 95616
3 Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599
4 Reproductive Toxicology Division, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711
5 Environmental Toxicology Division, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711

* To whom correspondence should be addressed. E-mail: bllasley{at}ucdavis.edu.


  Abstract

Bromodichloromethane (BDCM) is a trihalomethane found in drinking water as a by-product of disinfection processes. BDCM is hepatotoxic and nephrotoxic in rodents and has been reported to cause strain-specific full-litter resorption in F344 rats during the luteinizing hormone-dependent phase of pregnancy. In humans, epidemiological studies suggest an association between exposure to BDCM in drinking water and increased risk of spontaneous abortion. To begin to address the mechanism(s) of BDCM-induced spontaneous abortion, we hypothesized that BDCM targets the placenta. Primary cultures of human term trophoblast cells were used as an in vitro model to test this hypothesis. Trophoblasts were allowed to differentiate into multinucleated syncytiotrophoblast-like colonies, after which they were incubated for 24h with different concentrations of BDCM (20 nM to 2 mM). Culture media were collected and assayed for immunoreactive and bioactive chorionic gonadotropin (CG). Cultures exposed to BDCM showed a dose-dependent decrease in the secretion of immunoreactive CG as well as bioactive CG. The lowest effective BDCM concentration was 20 nM, approximately 35-times higher than the maximum concentration reported in human blood (0.57 nM). Trophoblast morphology and viability were similar in controls and cultures exposed to BDCM. We conclude that BDCM perturbs CG secretion by differentiated trophoblasts in vitro. This suggests that the placenta is a likely target of BDCM toxicity in the human and that this could be related to the adverse pregnancy outcomes associated with BDCM.

Key Words: bioactivity, chlorination, trihalomethanes, pregnancy .


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