1. 10 th AOTA CONGRESS Effect of Maternal Excessive Iodine Intake on Neurodevelopment and Cognitive Function in Rat Offspring Le Zhang Zhongyan Shan Weiping Teng Department of Endocrinology and Metabolism, First Affiliated Hospital of China Medical University Shenyang, China

2. 10 th AOTA CONGRESS Iodine is essential for the synthesis of thyroid hormone, especially during pregnancy Inadequate iodine intake during gestation results in thyroid hormone deficiency and permanent changes in the neurological and cognitive functions of offspring Background BMC Neuroscience 2010, 11:50 BMC Neuroscience 2009, 10:149

3. 10 th AOTA CONGRESS Background Thyroid diseases < 100 100~200 >200 Urinary iodine Level (μg/L) There have been few studies regarding maternal mildly excessive iodine intake and associated changes in the neurodevelopment of offspring Thyroid 2001,11(5):457 N Engl J Med 2006, 354(26):2783–2793 Neurotoxicology 2005, 26(3):417–426 ss

4. 10 th AOTA CONGRESS Background Our previous study Excessive iodine intake could increase the risk of subclinical hypothyroidism in offspring Chin Med J (Engl) 2004, 117(10):1518-1522

5. 10 th AOTA CONGRESS Our previous study Thyroid 2010, 20(8):909–915 Maternal overt and subclinical hypothyroidism affect the expression of BDNF Background

6. 10 th AOTA CONGRESS Neurotoxicology 2012, 33(4):842-852 Neurotoxicology 2005, 26(3):417-426 Neurotoxicol Teratol 2011, 33(4):464-472 G17PN7PN45 Background C-fos c-jun BDNF NSP-A C-fos c-jun BDNF NSP-A C-fos c-jun BDNF NSP-A C-fos c-jun BDNF NSP-A

7. 10 th AOTA CONGRESS Whether higher-than-normal iodine intake from before pregnancy until breastfeeding affects the postnatal neurodevelopment and cognitive function Objective

8. 10 th AOTA CONGRESS SPF female Wistar rats 80-120 g (n = 60) SPF female Wistar rats 80-120 g (n = 60) normal iodine (n=20) (NI, 140 μg /L KIO 3 ) PN45 PN7 G17 Materials AND Methods low iodine (n=20) (LI, deionized water) 3-fold iodine (n=20) (3HI, 480 μg /L KIO3) Pup Mother pre-pregnancy

9. 10 th AOTA CONGRESS Pup Materials AND Methods Morris Water Maze Test Arsenic cerium catalytic Spec- trophotometry Iodine content (urine, thyroid) Spatial memory Thyorid hormone C-fos C-jun BDNF NSP-A Chemilumines- Centimmuno- assay Immunohisto- chemistry Western blot Mother

10. 10 th AOTA CONGRESS Results Urinary and thyroidal iodine content *P < 0.05 compared with normal iodine control group

11. 10 th AOTA CONGRESS Maternal thyroid hormone *P < 0.05 compared with normal iodine control group Results

12. 10 th AOTA CONGRESS *P < 0.05 compared with normal iodine control group Pup thyroid hormone Results

13. 10 th AOTA CONGRESS Effect of 3HI on the protein expressions of c–Fos and c-Jun in the CA1 area of hippocampus Results *P < 0.05 compared with normal iodine control group

14. 10 th AOTA CONGRESS Effect of 3HI on BDNF and NSP-A expression in the hippocampus Results # P < 0.01 compared with the NI group on the same day; * P < 0.05 compared with the NI group on the same day

15. 10 th AOTA CONGRESS # P < 0.01 compared with the NI group on the same day; * P < 0.05 compared with the NI group on the same day Morris water maze (MWM) test Results

16. 10 th AOTA CONGRESS The offspring in the 3HI group may have a mildly impaired learning capacity, which could be associated with a decrease in BDNF and an increase in NSP-A levels The careful control of maternal iodine intake level is important to prevent neurodevelopmental defects in offspring Conclusion

17. 10 th AOTA CONGRESS