Xi Chuchu, Yang Zhao, Yu Yiyi, Li Shaoheng, He Jing, El-Aziz Tarek Mohamed Abd, Zhao Fang, Cao Zhengyu
Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China.
Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt; Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Ecotoxicol Environ Saf. 2022 May 1;236:113460. doi: 10.1016/j.ecoenv.2022.113460. Epub 2022 Apr 1.
Perinatal exposure to deltamethrin (DM) causes attention-deficit/ hyperactivity disorder-like behaviors. However, the vulnerable time window to DM exposure and the possible mechanism are obscure. We aimed to identify the critical window(s) at perinatal stages for DM exposure and the possible mechanism.
Pregnant mice were exposed to DM (0.5 mg/kg) at three different prenatal stages [gestational day (GD) 0-5, 6-15 and 16-birth (16-B)] and early postnatal stage (PD 0-10). Locomotor activity, learning and memory were evaluated using open field and Y-maze test, respectively. Nissl staining and western blots were used to examine the neuronal loss and the protein expression, respectively.
Perinatal exposures to DM had no effect on reproductive and growth index of offspring. However, mice receiving DM exposure during GD 16-B displayed significantly higher mortality suggesting GD 16-B is the most vulnerable time window to DM exposure. Prenatal but not early postnatal DM exposure impaired locomotor activity, learning and memory, and caused neuron loss in the dentate gyrus of male offspring. However, neither prenatal nor postnatal DM exposure affected mouse behavior of female offspring. Prenatal DM exposures decreased the protein levels of NR2A and NR2B in both hippocampi and cerebral cortices of male offspring. However, female mice receiving DM exposure at GD 16-B but not other stages displayed increased expression levels of NR2A and NR2B in hippocampi.
Prenatal but not early postnatal DM exposure impairs the neuron development in male but not female mice. Altered NMDA receptor expression may correlate to DM-induced behavioral deficits.
围产期接触溴氰菊酯（DM）会导致注意力缺陷/多动障碍样行为。然而，DM暴露的易感时间窗和可能的机制尚不清楚。我们旨在确定围产期DM暴露的关键时间窗和可能的机制。
将怀孕小鼠在三个不同的产前阶段[妊娠第（GD）0 - 5天、6 - 15天和16 - 出生（16 - B）]以及产后早期阶段（出生后第0 - 10天）暴露于DM（0.5mg/kg）。分别使用旷场试验和Y迷宫试验评估运动活动、学习和记忆。尼氏染色和蛋白质印迹分别用于检测神经元损失和蛋白质表达。
围产期接触DM对后代的生殖和生长指数没有影响。然而，在GD 16 - B期间接受DM暴露的小鼠死亡率显著更高，表明GD 16 - B是DM暴露最易感的时间窗。产前而非产后早期DM暴露损害了雄性后代的运动活动、学习和记忆，并导致齿状回神经元损失。然而，产前和产后DM暴露均未影响雌性后代的小鼠行为。产前DM暴露降低了雄性后代海马体和大脑皮质中NR2A和NR2B的蛋白质水平。然而，在GD 16 - B而非其他阶段接受DM暴露的雌性小鼠海马体中NR2A和NR2B的表达水平增加。
产前而非产后早期DM暴露损害雄性而非雌性小鼠的神经元发育。NMDA受体表达的改变可能与DM诱导的行为缺陷相关。
