title: Bromodichloromethane inhibits human placental trophoblast differentiation.
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 and 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.
authors.affiliation: Center for Health and the Environment, School of Medicine, University of California, Davis, California 95616, USA.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Chen
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
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Douglas
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007118:Immunoassay; D007365:Intercellular Junctions / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D011247:Pregnancy; D022882:Trihalomethanes / Q000633:toxicity*; D014327:Trophoblasts / Q000187:drug effects* / Q000648:ultrastructure; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D006063:Chorionic Gonadotropin; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical; C025191:bromodichloromethane; D007770:L-Lactate Dehydrogenase