Effect of iodine deficiency in pregnant rats on doublecortin and synaptophysin (p38) expressions of fetal brain / 中华内分泌代谢杂志

ABSTRACT

ObjectiveTo investigate the effects of maternal thyroid dysfunction during pregnancy caused by iodine deficiency of different degrees on doublecortin ( DCX ) and synaptophysin ( p38 ) expressions in fetal brain.Methods Wistar female rats were randomly divided into four groupsadequate iodine ( AI),mild iodine deficiency ( MiID ),moderate iodine deficiency ( MoID ),and severe iodine deficiency ( SID ),according to the total daily iodine supply( fed on an iodine deficient diet with different dosages of KI added in drinking water).Three months later the rats were mated.Serum TSH and thyroid hormones were determined in maternal rats on gestational day 20 using chemiluminescent immunoassay.The iodine contents in urine and histological changes of thyroid gland were observed in pregnant rats.The mRNA and protein levels of DCX and synaptophysin ( p38 ) were analyzed in fetal brain by using real time quantitative RT-PCR and western blotting respectively.Results( 1 ) Iodine contents in urine of pregnant rats were reduced with the decrease of their iodine supply.Compared with group AI,serum TSH was significantly increased [ ( 2.95 ± 1.70 vs 1.31 ± 0.55 ) mU/L,P ＜ 0.05 ],and both TT4 and FT4 were significantly decreased [ ( 14.3±4.1 vs 28.4±19.3 ) nmol/L,P＜0.05 ] and [ ( 10.8±3.6 vs 20.2±8.0) pmol/L,P＜0.01 ] in pregnant rats of SID group.Whereas,a slight rise in TSH,and a mild decline in both TT4and FT4 were found in MoID and MiID groups.However,there were no significant changes in TT3 and FT3 levels among these four groups.( 2 )Histological characteristics of thyroid gland in pregnant rats showed a typical goiter with small follicular hyperplasia and lack of colloid in SID group,moderate follicular hyperplasia with decreased colloid in MoID group; but mild cellular hyperplasia without decrease in follicular size and colloid in MiID group.( 3 ) The mRNA levels of DCX were increased in fetal brains of three iodine deficiency groups compared with AI group,but a statistical significance was found in MoID group.The protein levels of DCX in all experiment groups were significantly increased.Both mRNA and protein expressions of synaptophysin ( p38 )were significantly down-regulated in three iodine deficiency groups.Conclusions Maternal thyroid dysfunction caused by iodine deficiency,even by mild or moderate iodine deficiency,may lead to retardation of fetal neuronal and synaptic growth.