Bromodichloromethane inhibits human placental trophoblast differentiation
Bromodichloromethane inhibits human placental trophoblast differentiation
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DOI：
10.1093/toxsci/kfh046
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发表时间：
2004-03-01
影响因子：
3.8
通讯作者：
Douglas, GC
中科院分区：
文献类型：
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作者：
Chen, JG;Thirkill, TL;Douglas, GC
流行病学数据表明，接触溴二氯甲烷（BDCM）（一种因饮用水消毒而在饮用水中发现的三卤甲烷）与自然流产风险增加之间存在关联。我们之前假设 BDCM 以胎盘为目标，并表明暴露于 BDCM 的人类足月合体滋养层原代培养物中绒毛膜促性腺激素 (CG) 的分泌减少。在本研究中，我们通过评估 BDCM 对单核细胞滋养层细胞向多核合体滋养层样集落形态分化的影响来扩展这一观察。通过桥粒和细胞核的免疫细胞化学染色测定，向细胞滋养层培养物中添加 BDCM 以剂量依赖性方式抑制随后的多核集落的形成。 BDCM 浓度在 0.02 至 2 mM 之间时可观察到该效果，并通过定量图像分析得到证实。在这些培养条件下，生物活性和免疫反应性绒毛膜促性腺激素的分泌也以剂量依赖性方式显着受到抑制，并且CG的细胞水平也降低。滋养层活力并未因暴露于 BDCM 而受到损害。我们得出结论，BDCM 会破坏合体滋养层形成并抑制体外 CG 分泌。尽管不排除其他组织目标，但这些数据证实了 BDCM 以胎盘为目标的观点，并且可能对了解与人类暴露 BDCM 相关的不良妊娠结局具有影响。
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.