Pregnancy loss in the rat caused by bromodichloromethane
Pregnancy loss in the rat caused by bromodichloromethane
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DOI：
10.1093/toxsci/59.2.309
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发表时间：
2001-02-01
影响因子：
3.8
通讯作者：
Narotsky, MG
中科院分区：
文献类型：
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作者：
Bielmeier, SR;Best, DS;Narotsky, MG
溴二氯甲烷（BDCM）是一种三卤甲烷，是饮用水氯化的副产品。在最近的一项流行病学研究中，孕妇食用BDCM与自然流产风险增加有关。我们以前已经表明，BDCM导致妊娠丢失，即，在F344大鼠中的完全升降器吸收（FLR）。对作用方式进行了调查，主要结果有三个。首先，F344和Sprague-Dawley（SD）大鼠品系之间的敏感性存在显著差异。在妊娠第6-10天（GD）水溶液灌胃给药后，75 mg/kg/天剂量组F344大鼠的FLR发生率为62%，而所有SD大鼠均保持其窝仔数。第二，关键期包括促黄体生成素（LH）依赖期妊娠。在GD 6-10以75 mg/kg/天剂量给药的大鼠的FLR发生率为75%，但在GD 11-15以75或100 mg/kg/天剂量给药的大鼠未受影响。第三，单次给药后24小时，所有FLR母鼠的血清孕酮水平均显著降低，但LH水平未受影响。LH依赖期的高FLR率，此后缺乏反应，以及孕酮水平降低而LH水平无相关降低表明BDCM破坏了黄体对LH的反应性。
Bromodichloromethane (BDCM), a trihalomethane, is a byproduct of the chlorination of drinking water. In a recent epidemiological study, consumption of BDCM was associated with an increased risk of spontaneous abortion in pregnant women. We have previously shown that BDCM causes pregnancy loss, i.e., full-lifter resorption (FLR), in the F344 rat. The mode of action was investigated, with three main findings. First, there was a dramatic difference in sensitivity between F344 and Sprague-Dawley (SD) rat strains. Following aqueous gavage treatment on gestational days (GD) 6-10, F344 rats had a 62% incidence of FLR at 75 mg/kg/day, whereas all SD rats maintained their litters. Second, the critical period encompassed the luteinizing hormone (LH)-dependent period of pregnancy. Rats treated on GD 6-10 at 75 mg/kg/day had a 75% incidence of FLR, but rats treated on GD 11-15 at 75 or 100 mg/kg/day were unaffected. Third, 24 h after a single dose, all dams with FLR had markedly reduced serum progesterone levels; however, LH levels were unaffected. The high FLR rate during the LH-dependent period, the lack of response thereafter, and the reduced progesterone levels without an associated reduction in LH levels suggests that BDCM disrupts luteal responsiveness to LH.