十溴联苯醚(BDE 209)孕哺期及出生后暴露对子代小鼠血液系统影响初探

本研究旨在探讨BDE 209长期暴露对出生后不同发育阶段子鼠血液系统的影响。将75只雌性昆明小鼠随机分为对照组、低剂量组(1.5 mg·kg-1·d-1)和高剂量组(225 mg·kg-1·d-1)。BDE 209暴露10 d后,将雌鼠与雄鼠合笼。选取怀孕时间相近(相差不过2 d)的10只孕鼠持续染毒直至自然分娩。出生后子鼠在哺乳期通过母乳染毒,断乳后则按照与母鼠相同的方式进行染毒,并在不同时间点进行外周血常规、外周血形态学、骨髓细胞形态学、骨髓细胞染色体组型和数目分析。血常规结果显示,低、高剂量BDE 209暴露对出生后不同发育阶段子鼠的白细胞计数没有影响,即白细胞、中性粒细胞、淋巴细胞及单核细胞的数量均无显著变化(P0.05);红细胞系统检查显示一定性别差异,即低剂量和高剂量BDE 209染毒的雄性小鼠在PND30出现红细胞(RBC)(P0.05)、血红蛋白(Hb)(P0.05或P0.01)及红细胞压积(P0.05或P0.01)的显著降低;而雌性小鼠只在PND 30出现红细胞压积的降低(P0.05);在PND 30,高剂量暴露组的雌性及雄性小鼠,低剂量暴露组的雌性小鼠均出现血小板计数的显著降低(P0.05或P0.01);而PND 60、PND 90的实验组血小板均未观察到显著改变(P0.05)。外周血形态学检查表明,低剂量组在PND 30、PND 60,及高剂量组在PND 90检测到典型异常结果多表现为白细胞数的增多。而低剂量组在PND 90检测到的典型异常结果多表现为异型深染淋巴细胞(P0.05)。骨髓形态学检测表明,低剂量组子代雄性及雌性小鼠在PND 60、PND 90骨髓涂片可检测到骨髓细胞的异常结果,表现为骨髓增生活跃,高剂量组雄性小鼠在PND 90观察到3例异常涂片,表现为骨髓增生异常(P0.05)。研究结果表明,BDE 209长期暴露可能导致出生子代外周血和骨髓的毒性,提示具有血液系统发育毒性。

The Effect of Perinatal and Post-birth Exposure of BDE 209 on the Developmental Hematological System in Offspring Mice

To explore the effect of perinatal and post-birth exposure of BDE 209 on the developmental hematological system in offspring mice, we randomly assigned 75 Kunming female mice to the control and two experimental groups through gavage for 10 days before mating. Ten mice with the similar fertilization day were selected for each group and continued to gavage through pregnancy and lactation, until weaning. Then the offspring mice were exposed following the same exposure protocol. The peripheral blood routine and morphology, bone marrow karyotyping and number were analyzed at different PND. The results showed that no significant difference was observed in the number of white blood cells, neutrophile granulocytes, lymphocytes and mononuclear cells (P > 0.05). The gender difference was found in the red blood system in both low and high BDE 209 groups, that is, the cell counts, hemoglobin and hematokrit were significantly decreased in the male mice at PND 30 (P<0.05 or P < 0.01), while only the red cell count was decreased significantly in the female mice (P < 0.05). At PND 30, the number of thrombocytes was significantly decreased in the male mice of both exposure groups and the female mice of low BDE 209 exposure (P < 0.05 or P < 0.01). However, no significant changes were observed on PND 60 and 90 (P > 0.05). The morphological examination on the peripheral blood showed that the number of white blood cells was increased at PND 30 and 60 in low BDE 209 exposure, and at PND 90 in high BDE 209 exposure. In addition, exposure to low dose BDE 209 resulted in increased hyperchromatic lymphocytes at PND 90 (P < 0.05). The morphological examination on the bone marrow showed hyperplasia in both male and female mice at PND 60 and 90 in low BDE 209 exposure group, while bone marrow hyperplasia was found in 3 male mice at PND 90 in high BDE 209 exposure (P < 0.05). Our data suggest that perinatal and post-birth exposure of BDE 209 may lead to developmental toxicity on the hematological system of offspring mice including some adverse effects in peripheral blood and bone marrow system.