Excess iodine exposure:An emerging area of concern for male reproductive physiology in the post-salt iodization era

To prevent iodine deficiency disorders,the universal salt iodization programme has been introduced all over the globe,including environmentally iodine sufficient regions irrespective of their iodine status.As a result,iodine-induced thyroid dysfunctions namely hyperthyroidism,hypothyroidism,autoimmune thyroid diseases,endemic goiter and even thyroid cancer including infertility,still births,abortions and embryo toxicity have emerged as a major public health problem.In other words,the consequence of iodine deficiency and excess is almost‘U’-shaped.Hypothyroidism caused by iodine deficiency affects reproductive functions of organisms;however,such undesirable effects of iodine overload on male gonadal physiology together with hormonal profiles are yet to be adequately explored.The discovery of iodide transporter in the testis justifies an independent role of iodine in male reproductive function,which is not entirely known.Recent studies on human subjects and animal models are now revealing further perceptions into the effect of excess iodine on male infertility with euthyroid status.Excess iodine exposure has been linked with deterioration of structural and functional changes of testis leading to compromised spermatogenesis by affecting various cellular and molecular signaling pathways culminating into disrupted the blood-testis barrier and cytoskeleton.This review provides an update and summarizes various novel insights of excess iodine exposure on reproduction by establishing the independent role of iodine on male reproductive endocrinology,which might help in formulating future strategies to prevent iodine-induced male infertility,an emerging global concern,especially in the post-salt iodization era.

Effect of Selenium Supplementation on Activity and mRNA Expression of Type 1 Deiodinase in Mice With Excessive Iodine Intake

Objective To investigate the effect of selenium supplementation on the selenium status and selenoenzyme, especially the activity and mRNA expression of type 1 deiodinase （D1） in mice with excessive iodine （EI） intake and to explore the mechanism of selenium intervention on iodine-induced abnormities. Methods Weanling female BALB/c mice were given tap water or 3 mg/L of iodine or supplemented with 0.5 mg/L or 1.0 mg/L of selenium in the presence of excessive iodine for 5 months. Selenium status, thyroid hormone level, hepatic and renal D 1 activity and mRNA expression were examined. Results Excessive iodine intake significantly decreased the selenium concentration in urine and liver, and the activity of glutathione peroxidase （GSH-Px） in liver. Meanwhile, serum total T4 （TT4） increased while serum total T3 （TT3） decreased. Hepatic D1 enzyme activity and mRNA expression were reduced by 33% and 86%, respectively. Renal D1 enzyme activity and mRNA were reduced by 30% and 55%, respectively. Selenium supplementation obviously increased selenium concentration, activity of GSH-Px and D1 as well as mRNA expression of D1. However, increasing the supplementation of Se from 0.5 to 1.0 mg/L did not further increase selenoenzyme activity and expression. Conclusion Relative selenium deficiency caused by excessive iodine plays an essential role in the mechanism of iodine-induced abnormalities. An appropriate dose of selenium supplementation exercises a beneficial intervention.

Effect of Excessive Iodine on Immune Function of Lymphocytes and Intervention with Selenium

In order to study the effect of excessive iodine on immune function of lymphocytes and the role of selenium supplementation with excessive iodine intake, the changes of T lymphocyte number, ratio of subsets, activity of natural killer （NK） cells and lymphocytes proliferation response were investigated. 150 female BALB/C mice were randomly divided into 5 groups in terms of their body weight （n=30 in each group）, and 10 of each group were taken as one batch for test. Mice in the 5 groups were orally administrated with iodine 0 （group Ⅰ ）, 1500 （group Ⅱ）, 3000 （group Ⅲ）, 6000 μg/L （group ）, iodine 6000 μg/L plus selenium 0.3 mg/L （group Ⅴ） respectively for 30 days. Lymphocyte proliferation response, CD4^＋/CD8^＋, Th1/Th2 and the activity of NK cells were measured. CD4^＋/CD8^＋ was significantly lower, while lymphocyte proliferation response stronger, and Th1/Th2 and the activity of NK cells significantly higher in group Ⅳ than in group Ⅰ （P〈0.01）. There was no significant difference in all indexes between group Ⅴ and group Ⅰ （P〉0.05）. It was suggested that excessive iodine as exogenous chemical materials can induce disorders of T lymphocyte immune function in mice. 0.3 mg/L selenium supplementation can protect mice against toxicity induced by 6000 μg/L iodine.

Polyinosine-polycytidylic acid promotes excessive iodine intake induced thyroiditis in non-obese diabetic mice via Toll-like receptor 3 mediated inflammation

Background Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors （TLRs） have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine- polycytidylic acid （poly（I：C）） promoting excessive iodine intake induced thyroiditis in non-obese diabetic （NOD） mice. Methods Both NOD and BALB/c mice were randomly assigned to four groups： control group （n=5）, high iodine intake （HI） group （n=7）, poly（I：C） group （n=7） and combination of excessive iodine and poly（l：C） injection （HIP） group （n=7）. After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3＋ cells and TLR3 as well as inflammatory mRNA level were evaluated. Results Both NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofiuorescence staining results displayed a large number of CD3~ cells in HIP NOD mice. Real-time polymerase chain reaction （PCR） results suggested interferon （IFN）-a increased over 30 folds and IFN-y expression was doubled compared with control group, but interleukin （IL）-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine （TT4） and increased thyroid-stimulating hormone （TSH） was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression. Conclusion Poly（l：C） enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.

Type 1 iodothyronine deiodinase activity and mRNA expression in rat thyroid tissue with different iodine intakes

Background Type 1 deiodinase （D1） plays an important role in the metabolism of thyroid hormone and has close relationship with thyroid function. In this study we explore the effects of iodine intake on D1 activity and its mRNA expression and its possible mechanism. Methods Forty-eight Wistar rats were randomly divided into six groups with 8 in each： low iodine （LI）, normal iodine （NI）, five-fold iodine （HI5）, ten-fold iodine （HI10）, fifty-fold iodine （HI50）, one hundred-fold iodine （HI100） group. Three months, six months and twelve months after admistration of potassium iodate, they were sacrificed and thyroids were excised. The expression of D1 mRNA in the thyroid tissue was determined by RT-PCR and D1 activity was analyzed by ^125I-rT3 as substrate. The thyroid hormone was measured with radioimmunoassay method. Results Compared with NI group, D1 mRNA expression in LI groups slightly decreased, and D1 activity greatly increased. Both T3 and T4 in thyroid tissue significantly decreased, but the T3/T4 ratio increased. D1 mRNA expression decreased in all HI groups, and D1 activity was significantly lower in HI groups. There was a tendency of decrease in D 1 activity with increased doses of iodine intakes. There was no significant difference in T4 in thyroid tissue between HI groups and NI group, but a tendency of decrease in T3 level was found in all HI groups. Conclusions In the case of iodine deficiency, D 1 activity increased greatly in order to convert more T4 to T3. Excess iodine can inhibit both D1 mRNA expression and its activity to protect organism from being injured by excessive T3.