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ToxSci Advance Access published online on December 22, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfh046
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received September 16, 2003; accepted November 19, 2003
© 2003 Society of Toxicology

Reproductive and Developmental Toxicology

Bromodichloromethane Inhibits Human Placental Trophoblast Differentiation

Jiangang Chen 1, 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, Bill L. Lasley 1, and Gordon C. Douglas 2*

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 of 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: gcdouglas{at}ucdavis.edu.


  Abstract

Epidemiological data suggest an association between exposures to bromodichloromethane (BDCM), a trihalomethane found in drinking water as a result of drinking water disinfection, and an increased risk of spontaneous abortion. We previously hypothesized that BDCM targets the placenta and showed that the secretion of chorionic gonadotrophin (CG) was reduced in primary cultures of human term syncytiotrophoblasts exposed to BDCM. In the present study we extend this observation by evaluating the effects of BDCM on the morphological differentiation of mononucleated cytotrophoblast cells to multinucleated syncytiotrophoblast-like colonies. Addition of BDCM to cytotrophoblast cultures inhibited the subsequent formation of multinucleated colonies in a dose-dependent manner as determined by immunocytochemical staining for desmosomes and nuclei. The effect was seen at BDCM concentrations between 0.02-2 mM and was confirmed by quantitative image analysis. Secretion of bioactive and immunoreactive chorionic gonadotropin was also significantly inhibited in a dose-dependent manner under these culture conditions and cellular levels of CG were also reduced. Trophoblast viability was not compromised by exposure to BDCM. We conclude that BDCM disrupts syncytiotrophoblast formation and inhibits CG secretion in vitro. Although other tissue targets are not ruled out, these data substantiate the idea that BDCM targets the placenta and could have implications for understanding the adverse pregnancy outcomes associated with BDCM exposure in humans.

Key Words: pregnancy, bioactivity, desmosomes, toxicity .


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