Department of Occupational and Environmental Health, Guilin Medical University , Guilin , Guangxi , People's Republic of China.
Guangxi Colleges and University Key Laboratory of Preventive Medicine, Guilin Medical University , Guilin , Guangxi , People's Republic of China.
Toxicol Mech Methods. 2019 Oct;29(8):569-579. doi: 10.1080/15376516.2019.1624906. Epub 2019 Jun 19.
The present study investigated the alterations in nerve function and its potential mechanism of offspring result from the decabromodiphenyl ether (BDE209) orally gavage (0, 1.5, and 225 mg/kg.d body weight) in pregnant and lactating mice. Weight gain and litter size of maternal mice and body weight of offspring were examined. Learning and memory abilities of offspring were tested by the Morris water maze experiment. Thyroid hormones (THs) concentrations in peripheral blood of offspring were detected by the chemiluminescence enzyme immunoassay. Relative mRNA expression of type 1 iodothyronine deiodinase (), type 2 iodothyronine deiodinase (), and type 3 iodothyronine deiodinase () in the livers and brains of offspring were measured by QRT-PCR (quantitative real-time polymerase chain reaction). Protein expression of in the livers and brains of offspring was measured by Western blot. All indexes of offspring were tested at postnatal day (PND) 21 and PND 60, respectively. As a result, administration of BDE209 decreased weight gain and litter size of maternal mice, and reduced body weight of offspring mice, prolonged escape latency and declined guardant time of offspring in the Morris water maze experiment. Moreover, BDE209 elevated serum levels of total thyroxine (T4), total triiodothyronine (T3), free T4, and free T3 in offspring. In addition, maternal exposure to BDE209 inhibited , , mRNA expression in the livers of offspring, while elevated mRNA expression and reduced mRNA expression in the brains of offspring. BDE209 also inhibited the protein expression of in the livers and brains of offspring. These results indicate that BDE209 exposure to pregnant and lactating mice can cause disruption in serum THs of offspring by altering mRNA and protein expression of iodothyronine deiodinases, which might consequently result in neurologic impairment of offspring mice.
本研究旨在探讨经口灌胃（0、1.5 和 225mg/kg.d 体重）十溴联苯醚（BDE209）对孕哺期母鼠及其子代神经功能的影响及其潜在机制。检测母鼠体重增长、产仔数和仔鼠体重，Morris 水迷宫实验检测仔鼠学习记忆能力，化学发光酶免疫分析法检测仔鼠外周血甲状腺激素（THs）浓度，定量实时聚合酶链反应（QRT-PCR）检测仔鼠肝脏和脑组织中Ⅰ型碘甲状腺原氨酸脱碘酶（）、Ⅱ型碘甲状腺原氨酸脱碘酶（）和Ⅲ型碘甲状腺原氨酸脱碘酶（）相对 mRNA 表达，Western blot 法检测仔鼠肝脏和脑组织中蛋白表达。所有指标均在仔鼠出生后第 21 天（PND21）和第 60 天（PND60）进行检测。结果显示，BDE209 处理降低了母鼠体重增长和产仔数，减少了仔鼠体重，延长了 Morris 水迷宫实验中仔鼠的逃避潜伏期，降低了仔鼠的警戒时间。此外，BDE209 增加了仔鼠血清总甲状腺素（T4）、总三碘甲状腺原氨酸（T3）、游离 T4 和游离 T3 的水平。此外，母鼠暴露于 BDE209 抑制了子代肝脏中、和的 mRNA 表达，而增加了脑内的 mRNA 表达，降低了的 mRNA 表达。BDE209 还抑制了仔鼠肝脏和脑组织中蛋白的表达。这些结果表明，BDE209 暴露于孕哺期母鼠可通过改变碘甲状腺原氨酸脱碘酶的 mRNA 和蛋白表达，导致仔鼠血清 THs 紊乱，从而导致仔鼠神经功能受损。
