title: Effect of bromodichloromethane on chorionic gonadotrophin secretion by human placental trophoblast cultures.
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 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.
authors.affiliation: Center for Health and the Environment, School of Medicine, University of California, Davis 95616, USA.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Chen
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Douglas
authors.forename: Twanda L
authors.initials: TL
authors.lastname: Thirkill
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lohstroh
authors.forename: Susan R
authors.initials: SR
authors.lastname: Bielmeier
authors.forename: Michael G
authors.initials: MG
authors.lastname: Narotsky
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Best
authors.forename: Randy A
authors.initials: RA
authors.lastname: Harrison
authors.forename: Kala
authors.initials: K
authors.lastname: Natarajan
authors.forename: Rex A
authors.initials: RA
authors.lastname: Pegram
authors.forename: James W
authors.initials: JW
authors.lastname: Overstreet
authors.forename: Bill L
authors.initials: BL
authors.lastname: Lasley
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D022882:Trihalomethanes / Q000633:toxicity*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D006063:Chorionic Gonadotropin; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical; C025191:bromodichloromethane