Wen Ya, Ding Xingwang, Guan Quanquan, Hu Weiyue, Wang Bingqian, Hu Qi, Bigambo Francis Manyori, Zhou Zhu, Wang Xu, Xia Yankai
State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Chemistry, York College, City University of New York, New York 11451, USA.
Ecotoxicol Environ Saf. 2021 Jun 1;215:112142. doi: 10.1016/j.ecoenv.2021.112142. Epub 2021 Mar 17.
The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5-21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group. Our data showed that prenatal PM exposure caused the offspring mice's anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.
神经系统的发育对儿童健康至关重要。然而，神经系统在发育过程中也易受多种因素影响。迄今为止，流行病学研究报告了孕期接触颗粒物（PM）与神经行为发育之间关系的有争议结果。因此，我们研究了孕期暴露于PM对后代神经行为发育的影响。成年C57BL/6小鼠从妊娠第0.5天至21天通过气管内滴注暴露于PM。每日暴露剂量分别为250μg/kg体重和2500μg/kg体重。后代小鼠在第5周开始行为测试。我们使用RNA测序评估神经行为发育以及小鼠海马体中的基因表达水平变化。在旷场试验中，高剂量组中央区域的移动距离显著降低。产前高剂量PM暴露的雄性后代小鼠血清游离三碘甲状腺原氨酸（FT3）水平显著升高。RNA测序结果表明，高剂量组后代小鼠甲状腺激素信号通路中的Prkca、Med12l、Ep300和Slc16a10显著降低。我们的数据表明，产前PM暴露导致后代小鼠出现焦虑样行为并使血清FT3水平升高。甲状腺激素通路相关基因的变化可能是上述一系列变化的原因。
