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EFFECT OF BROMODICHLOROMETHANE ON HUMAN TROPHOBLAST CHORIONIC GONADOTROPHIN SECRETION
Citation:
Chen, J., T. L. Thirkill, P. N. Lohstroh, S. R. Bielmeier, M G. Narotsky, D S. Best, R. A. Harrison, K. Natarajan, R A. Pegram, G. C. Douglas, AND B. L. Lasley. EFFECT OF BROMODICHLOROMETHANE ON HUMAN TROPHOBLAST CHORIONIC GONADOTROPHIN SECRETION. Presented at Endocrine Society, Philadelphia, PA, June 19-22, 2003.
Description:
Effect of Bromodichloromethane on Human Trophoblast Chorionic Gonadotrophin Secretion
Jiangang Chen1, Twanda L. Thirkill1, Peter N. Lohstroh1, Susan R. Bielmeier2, Michael G. Narotsky3, Deborah S. Best3, Randy A. Harrison3, Kala Natarajan1, Rex A. Pegram3, Gordon C. Douglas1, Bill L. Lasley1.
1 University of California, Davis, California
2 University of North Carolina, Chapel Hill, North Carolina
3 US Environmental Protection Agency, ORD, Research Triangle Park, North Carolina
Bromodichloromethane (BDCM) is a trihalomethane found in drinking water as a result of disinfection. BDCM is hepatotoxic and nephrotoxic and has been reported to cause full-litter resorption in rats during the luteinizing hormone-dependent period of pregnancy. Epidemiological studies suggest an association between exposure to BDCM in drinking water and an increased risk of spontaneous abortion. To begin to understand the mechanism(s) of BDCM-induced spontaneous abortion, we hypothesized that BDCM affects the morphological differentiation of placental trophoblasts and the secretion of trophoblast-derived chorionic gonadotrophin (CG). Primary cultures of human term trophoblast cells were used as an in vitro model to test this hypothesis. To study effects on trophoblast differentiation (i.e., formation of multinucleated syncytiotrophoblast-like colonies), BDCM (2 mM) was added to culture medium; immunocytochemical assessment after 72 hr indicated that differentiation was neither blocked nor enhanced. To study the effect of BDCM on CG secretion, trophoblasts were first allowed to differentiate in differentiation-inducing medium for 48 hr and then cultured in medium containing BDCM (20 nM to 2 mM) for an additional 24 hr. Compared to control, a BDCM dose-dependent decrease in the secretion of immunoreactive CG as well as bioactive CG was observed. CG secretion was affected at 20 nM, approximately 35-times higher than reported in human blood. We conclude that BDCM perturbs CG secretion by differentiated trophoblasts in vitro, and that this could be related to the adverse pregnancy outcomes associated with BDCM.
[This abstract does not necessarily reflect EPA policy.]