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BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION
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, B. L. Lasley, AND G. C. Douglas. BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION. TOXICOLOGICAL SCIENCES 78(1):166-174, (2004).
Description:
BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL
TROPHOBLAST DIFFERENTIATION
Jiangang Chen, Twanda L. Thirkill, Peter N. Lohstroh, Susan R. Bielmeier, Michael
G. Narotsky, Deborah S. Best, Randy A. Harrison, Kala Natarajan, Rex A. Pegram,
Bill L. Lasley, and Gordon C. Douglas.
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.