ToxSci Advance Access originally published online on September 11, 2003
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Toxicological Sciences 76, 75-82 (2003)
Copyright © 2003 by the Society of Toxicology
ENDOCRINE TOXICOLOGY |
Effect of Bromodichloromethane on Chorionic Gonadotrophin Secretion by Human Placental Trophoblast Cultures
* Center for Health and the Environment and
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616;
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599;
Reproductive Toxicology Division and
¶ Environmental Toxicology Division, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
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 24 h 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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