孕哺期噻虫胺暴露对母鼠甲状腺功能与子代早期神经发育的影响

Effects of clothianidin exposure during pregnancy and lactation on the thyroid function of maternal rats and the early neurodevelopment of offspring

  • 摘要: 目的: 通过建立Sprague-Dawley(SD)大鼠孕哺期噻虫胺(CLO)暴露模型,探究其对母鼠甲状腺功能与子代早期神经发育的影响。方法: 将成功受孕的大鼠随机分为4组,分别为对照组、低剂量组(20 mg·kg-1·d-1 CLO)、中剂量组(65 mg·kg-1·d-1CLO)和高剂量组(130 mg·kg-1·d-1 CLO),每组10只。于妊娠当天至产后21 d,按5 mL/kg大鼠体质量的剂量灌胃染毒,1次/d,监测孕期体质量,产后7~9 d仔鼠进行平面翻正、负趋地性和悬崖回避等早期神经反射试验。采用苏木精—伊红(HE)染色法观察母鼠甲状腺病理形态变化,化学发光法检测母鼠甲状腺功能5项指标:血清促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT3)、游离三碘甲状腺原氨酸(FT3)、总四碘甲状腺原氨酸(TT4)、游离四碘甲状腺原氨酸(FT4)水平。结果: 与对照组相比,高剂量组母鼠孕期体质量增长率显著下降(P<0.05),中、高剂量组母鼠肝脏的脏器系数显著升高(P<0.05)。HE染色显示,中、高剂量组母鼠甲状腺滤泡结构受损,且滤泡内胶质含量降低。中、高剂量组母鼠血清TSH、TT4和FT4水平较对照组降低(P<0.05),而TT3、FT3水平与对照组比较,无显著差异(P>0.05)。中、高剂量组仔鼠体质量均较对照组降低(P<0.001)。高剂量组仔鼠平面翻正、悬崖回避反射时间,以及各剂量组的负趋地性反射时间均较对照组延长(P<0.05)。结论: 孕哺期暴露于CLO不仅可能对母体脏器造成损伤,还会干扰其甲状腺激素水平的稳态,进而对子代的早期体格发育和神经发育产生不良影响。

     

    Abstract: Objective: To investigate the effects of clothianidin(CLO) exposure on the thyroid function of maternal rats and the early neurodevelopment of their offspring by establishing a CLO exposure model in SpragueDawley(SD) rats during pregnancy and lactation. Methods: Rats with confirmed pregnancy were randomly divided into 4 groups: control group, low-dose group(20 mg·kg-1·d-1 CLO), medium-dose group(65 mg·kg-1·d-1 CLO), and high-dose group(130 mg·kg-1·d-1 CLO), with 10 rats per group. From the day of pregnancy to postnatal day 21, the rats were administered the test substance via oral gavage once daily at a volume of 5 mL/kg body mass, and their body mass were monitored. For the offspring rats, early neurobehavioral reflex tests including surface righting reflex, negative geotaxis, and cliff avoidance reflex, were conducted on postnatal days 7 and 9. Morphological changes of the thyroid tissue in maternal rats were observed via hematoxylin-eosin(HE) staining. Chemiluminescence immunoassay was used to detect the levels of five serum thyroid function indices in maternal rats, including thyroid-stimulating hormone(TSH), total triiodothyronine(TT3), free triiodothyronine(FT3), total tetraiodothyronine(TT4), and free tetraiodothyronine(FT4). Results: Compared with the control group, the maternal rats in the high-dose group showed a significant decrease in the mass gain rate during pregnancy(P<0.05), while the liver organ coefficients of maternal rats in the medium-dose and high-dose groups were significantly increased(P<0.05). HE staining revealed that the thyroid follicular structure was impaired and intrafollicular colloid content was reduced in the maternal rats of the medium-dose and high-dose groups. In terms of maternal serum thyroid function indices, the levels of TSH, TT4, and FT4 in the medium-dose and high-dose groups were significantly lower than those in the control group(P<0.05), while no significant differences were observed in the levels of TT3 and FT3 between the dose groups and the control group(P>0.05). For the offspring rats, the body mass of offspring in the medium-dose and high-dose groups was significantly lower than those in the control group(P<0.001). The reflex latencies of surface righting reflex and cliff avoidance reflex in the offspring of the high-dose group, as well as the reflex latency of negative geotaxis in all dose groups, were significantly prolonged compared with the control group(P<0.05). Conclusion: Exposure to CLO during pregnancy and lactation may not only induce damage to maternal organs but also disrupt the homeostasis of maternal thyroid hormone levels, thereby exerting adverse effects on the early physical development and neurodevelopment of their offspring.

     

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