Ding Yong, Jia Li-na, Yang Bin, Zhang Gang, Wang Hai-yang, Guo Wei-wei, Jia Xiao-fang, Ge Cui-cui, Zhang Qin-li, Niu Qiao
Department of Occupational Medicine, Shanxi Medical University,Taiyuan 030001, China. E-mail:
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2013 Oct;31(10):744-8.
To observe the effects of maternal exposure to nano-alumina during pregnancy on the neurodevelopment in offspring mice.
Female ICR mice began to be exposed to nano-alumina 10 d before mating, and the nano-alumina exposure lasted till offspring mice were born. All the female mice were randomly divided into 5 groups: solvent control group (saline), nano-carbon group (11.76 mg/ml), micro-alumina group (50 mg/ml), 50 nm alumina group (50 mg/ml), and 13 nm alumina group (50 mg/ml). All the mice were treated by nasal drip (10 µl/time) 3 times daily till offspring mice were born. Physiological indices, reflex and sensory function test, endurance test, Morris water maze test, positioning and navigation test, and open field test were used to evaluate the neurodevelopment of newborn mice.
On day 28, the body weight of 13 nm alumina group (16.73±4.04 g) was significantly lower than that of solvent control group (20.45±2.50 g) (P<0.01); the 13 nm alumina group had significantly delayed time to ear opening compared with the solvent control group (4.91±0.78 d vs 4.45±0.50 d, P<0.01); compared with the solvent control group, the nano-carbon group, micro-alumina group, 50 nm alumina group, and 13 nm alumina group had significantly delayed time to eruption of teeth (10.05±0.23 d vs 10.32±0.48 d, 10.75±0.45 d, 10.32±0.47 d, and 10.79±0.49 d, P<0.05 or P<0.01). On days 4 and 7 after birth, compared with the solvent control group, other groups had significantly decreased proportions of mice which passed the cliff avoidance test (P < 0.05 or P < 0.01). On days 12 and 14 after birth, compared with the solvent control group, the nano-carbon group, 50 nm alumina group, and 13 nm alumina group had significantly reduced pre-suspension time in the endurance test (P < 0.05 or P < 0.01). The Morris water maze and positioning and navigation tests showed that the 13 nm alumina group had a significantly increased 5 d incubation period compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of platform crossings (P < 0.05 or P < 0.01). The open field test showed that the nano-carbon group and 13 nm alumina group had reduced numbers of rearings compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of modifications (P < 0.01).
Maternal exposure to nano-alumina (13 nm) during pregnancy has inhibitory effects on the physical development and early behavioral development in newborn mice and can also inhibit the learning and memory abilities and adaptability to new environment in offspring mice. The neurodevelopmental toxicity of nano-alumina to newborn mice increases as the particle sizes of nano-alumina decrease, which has been demonstrated by the endurance test and number of rearings.
观察孕期母体暴露于纳米氧化铝对仔鼠神经发育的影响。
雌性ICR小鼠在交配前10天开始暴露于纳米氧化铝，纳米氧化铝暴露持续至仔鼠出生。将所有雌性小鼠随机分为5组：溶剂对照组（生理盐水）、纳米碳组（11.76毫克/毫升）、微氧化铝组（50毫克/毫升）、50纳米氧化铝组（50毫克/毫升）和13纳米氧化铝组（50毫克/毫升）。所有小鼠每日滴鼻给药（10微升/次）3次，直至仔鼠出生。采用生理指标、反射和感觉功能测试、耐力测试、莫里斯水迷宫测试、定位和导航测试以及旷场测试评估新生小鼠的神经发育。
出生后第28天，13纳米氧化铝组小鼠体重（16.73±4.04克）显著低于溶剂对照组（20.45±2.50克）（P<0.01）；13纳米氧化铝组小鼠的耳张开时间明显晚于溶剂对照组（4.91±0.78天对4.45±0.50天，P<0.01）；与溶剂对照组相比，纳米碳组、微氧化铝组、50纳米氧化铝组和13纳米氧化铝组小鼠的出牙时间明显延迟（10.05±0.23天对10.32±0.48天、10.75±0.45天、10.32±0.47天和10.79±0.49天，P<0.05或P<0.01）。出生后第4天和第7天，与溶剂对照组相比，其他组通过避崖试验的小鼠比例显著降低（P<0.05或P<0.01）。出生后第12天和第14天，与溶剂对照组相比，纳米碳组、50纳米氧化铝组和13纳米氧化铝组在耐力测试中的前悬时间显著缩短（P<0.05或P<0.01）。莫里斯水迷宫测试和定位与导航测试表明，13纳米氧化铝组与溶剂对照组相比，潜伏期显著延长5天（P<0.05）；与溶剂对照组相比，其他组穿越平台的次数显著减少（P<0.05或P<0.01）。旷场测试表明，纳米碳组和13纳米氧化铝组与溶剂对照组相比，竖毛次数减少（P<0.05）；与溶剂对照组相比，其他组修饰次数显著减少（P<0.01）。
孕期母体暴露于纳米氧化铝（13纳米）对新生小鼠的身体发育和早期行为发育有抑制作用，还可抑制仔鼠的学习记忆能力和对新环境的适应能力。纳米氧化铝对新生小鼠的神经发育毒性随纳米氧化铝粒径减小而增加，这在耐力测试和竖毛次数中得到证实。
