Effect of excessive iodine exposure on the placental deiodinase activities and Hoxc8 expression during mouse embryogenesis.
Excessive iodine induces thyroid dysfunction. However, the effect of excessive iodine exposure on maternal-fetal thyroid hormone metabolism and on the expression of genes involved in differentiation, growth and development is poorly understood. Since a thyroid hormone receptor response element was found in the Hoxc8 promoter region, Hoxc8 expression possibly regulated by excessive iodine exposure was firstly investigated. In the present study, Balb/C mice were given different doses of iodine in the form of potassium iodate (KIO3) at the levels of 0 (sterile water), 1.5, 3.0, 6.0, 12.0 and 24.0 microg/ml in drinking water for 4 months, then were mated. On 12.5 d postcoitum, placental type 2 and type 3 deiodinase activities and fetal Hoxc8 expression were determined. The results showed that excessive iodine exposure above 1.5 microg/ml resulted in an increase of total thyroxine and a decrease of total triiodothyronine in the serum of maternal mice, which was mainly associated with the inhibition of type 1 deiodinase activity in liver and kidney. Placental type 2 deiodinase activity decreased, showing an inverse relationship with maternal thyroxine level. Hoxc8 mRNA and protein expression at 12.5 d postcoitum embryos were down regulated. Because Hoxc8 plays an important role in normal skeletal development, this finding provides a possible explanation for the skeletal malformation induced by excessive iodine exposure and also provides a new clue to study the relationship between iodine or thyroid hormones and Hox gene expression pattern.
Yang
Xue F
XF
Department of Nutrition and Food Hygiene and MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, China.
Xu
Jian
J
Guo
Huai L
HL
Hou
Xiao H
XH
Hao
Li P
LP
Liu
Lie G
LG
Sun
Xiu F
XF
D000818:Animals; D004326:Drinking; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D007452:Iodates / Q000008:administration & dosage; D007453:Iodide Peroxidase / Q000378:metabolism*; D007455:Iodine / Q000009:adverse effects* / Q000652:urine; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000201:enzymology*; D017680:Potassium Compounds / Q000008:administration & dosage; D012333:RNA, Messenger / Q000032:analysis; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D000097564:Iodothyronine Deiodinase Type II
D018398:Homeodomain Proteins; D007452:Iodates; D007453:Iodide Peroxidase; D007455:Iodine; D017680:Potassium Compounds; D012333:RNA, Messenger; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C489816:Hoxc8 protein, mouse; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III; C039693:potassium iodate