Effects Of Exposure To Fenvalerate On Cognitive Behavior And Thyroid Signaling Pathway In Developing Brain In Mice

ObjectiveThere are growing evidences suggesting that environment endocrine disruptors can interfere with behavior development and thyroid function. Fenvalerate is a potential environment endocrine disruptor. The purpose of this study was to examine the impairments in behavior development and thyroid signaling pathway in mice exposed to fenvalerate during early life. MethodPregnant mice were orally administered with fenvalerate. Behavioral tests were performed to assess learning and memory performances and anxiety-related activities. RIA was used to examine thyroid hormone level in serum. Cerebral cortex of offspring and placenta was collected. RT-PCR was used to examine m RNA expressions of thyroid signaling pathway. ResultsCompared with control group, total distance in navigation test of Morris water maze in female fenvalerate-exposed group were increased significantly, and the difference was statistically significant(P < 0.05);latency of 2.00 mg/kg group increased, too(P < 0.05). In spatial probe test, times of crossing objective quadrant in female 0.20 mg/kg and 2.00 mg/kg fenvalerate groups were decreased significantly, and the difference was statistically significant(P < 0.05). Fenvalerate might not alter mice behaviors in open field test. In black and white alley test and elevated plus maze test, fenvalerate might disrupt mice behaviors slightly. Results showed that the level of D2 and D3 in cerebral cortex was significantly decreased in fenvalerate-exposed group; and the level of TRα1 m RNA expression was significantly decreased in mice exposed to fenvalerate. The expression of MCT8 was significantly decreased in 0.20 mg/kg group and the expression of OATP1C1 was significantly increased in 0.02 mg/kg, and decreased in 0.20 mg/kg group and 2.00 mg/kg group. The expression of BDNF and Neuro D was significantly decreased in fenvalerate-exposed group. In addition, the expression of MCT8 and TRβ1 in placenta was significantly decreased in fenvalerate-exposed 0.02 mg/kg and 2.00 mg/kg group. ConclusionEarly-life fenvalerate exposure may impair behavior development in mice through a mechanism of disrupting thyroid signaling pathway of cerebral cortex and placenta.