Chlormequat chloride inhibited thyroid hormone in the pregnant rats by regulating sodium/iodide symporter

Chlormequat chloride can increase agricultural production by making the stem of the crops shorter and stronger, so it has become one of the most popular growth regulators in the world and humans are widely exposed to it. However, besides its regulatory effects on the growth of the plants, our previous studies have demonstrated that chlormequat chloride can also affect maternal and embryonic homeostasis in the rats. To better understand the regulatory effect of chlormequat during pregnancy, in this study, pregnant rats were orally exposed to chlormequat chloride at 0, 0.05, 0.5 and 5 mg/kg.bw from gestation day (GD) 0-20, we found that levels of maternal thyroid hormones (THs) were inhibited on GD11 and the brain weight of the pups was affected on postnatal day (PD) 10. To understand the mechanisms of the decreases in THs, we found that the sodium/iodide symporter (NIS), which is responsible for the uptake of iodide by thyrocytes in the biosynthesis of THs, was inhibited in pregnant rats by chlormequat chloride dose-dependently. Furthermore, the thyrotropin (TSH) induced cAMP dependent protein kinase A (PKA) signaling pathway, which is the up-stream regulating pathway of NIS, was also inhibited by chlormequat chloride in the pregnant rats. However, the TSH-PKA-NIS pathway was not affected by chlormequat chloride in the non-pregnant female rats. To summarize, chlormequat chloride caused down-regulation of NIS and thus inhibited synthesis of maternal THs during embryonic development, and leads to altered postnatal brain weight.