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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 10th AOTA CONGRESS Background 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 BMC Neuroscience 2010, 11:50 BMC Neuroscience 2009, 10:149 10th AOTA CONGRESS ss Thyroid diseases Background < 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 10th 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 10th AOTA CONGRESS Background Our previous study Maternal overt and subclinical hypothyroidism affect the expression of BDNF Thyroid 2010, 20(8):909–915 10th AOTA CONGRESS Background NSP-A NSP-A C-fos C-fos c-jun c-jun BDNF BDNF G17 PN7 PN45 Neurotoxicology 2012, 33(4):842-852 Neurotoxicology 2005, 26(3):417-426 Neurotoxicol Teratol 2011, 33(4):464-472 10th AOTA CONGRESS Objective Whether higher-than-normal iodine intake from before pregnancy until breastfeeding affects the postnatal neurodevelopment and cognitive function 10th AOTA CONGRESS Materials AND Methods SPF female Wistar rats 80-120 g (n = 60) normal iodine (n=20) (NI, 140 μg /L KIO3) low iodine (n=20) (LI, deionized water) Mother pre-pregnancy G17 3-fold iodine (n=20) (3HI, 480 μg /L KIO3) Pup PN7 PN45 10th AOTA CONGRESS Materials AND Methods Mother Iodine content (urine, thyroid) Arsenic cerium catalytic Spectrophotometry Thyorid hormone ChemiluminesCentimmunoassay Pup C-fos C-jun Immunohistochemistry BDNF NSP-A Spatial memory Western blot Morris Water Maze Test 10th AOTA CONGRESS Results Urinary and thyroidal iodine content Urinary iodine concentration (μg/L) Thyroidal iodine concentration (μg/L) * 800 800 * 600 0 600 400 400 200 LI NI 3HI * 200 * 0 *P < 0.05 compared with normal iodine control group 10th AOTA CONGRESS Results Maternal thyroid hormone TT4 (μg/dL) * 7 35 6 * 5 25 20 3 15 * 1 * * * 10 * 5 0 0 pre-pregnancy G17 pre-pregnancy G17 LI NI 3HI * 1.4 1.3 1.2 1.1 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 30 4 2 TSH (mIU/L) FT4 (pmol/L) * pre-pregnancy G17 *P < 0.05 compared with normal iodine control group 10th AOTA CONGRESS Results Pup thyroid hormone TT4 (μg/dL) TSH (mIU/L) FT4 (pmol/L) LI NI 6 40 35 30 25 20 15 10 5 0 5 4 3 * * 2 1 0 PN7 PN45 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 0 * * PN7 * * PN45 3HI * PN7 PN45 *P < 0.05 compared with normal iodine control group 10th AOTA CONGRESS Results Effect of 3HI on the protein expressions of c–Fos and c-Jun in the CA1 area of hippocampus c-fos IOD Value (10 3) LI NI 14 3HI 12 10 8 * * 6 4 2 0 PN7 PN45 c-jun IOD Value (10 3) LI NI 3HI 14 12 10 8 6 * * 4 2 *P < 0.05 compared with normal iodine control group 0 PN7 10th AOTA PN45 CONGRESS Results Effect of 3HI on BDNF and NSP-A expression in the hippocampus BDNF immunoreactivity (Ratio to β-actin) 1.2 * * 1 0.8 NSP-A immunoreactivity (Ratio to β-actin) LI NI 1.4 1.2 3HI # # * 1 # # LI NI 3HI 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0 0 PN7 #P PN45 PN7 PN45 th the < 0.01 compared with the NI group on the same day; * P < 0.05 compared with the NI group10 on same day AOTA CONGRESS Results Morris water maze (MWM) test LI NI 3HI 140 Escape Latency(s) 120 * * 100 # 80 # * 60 # 40 20 1 2 3 4 5 Training Days #P < 0.01 compared with the NI group on the same day; * P < 0.05 compared with the NI group on the same day 10th AOTA CONGRESS Conclusion 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 10th AOTA CONGRESS 10th AOTA CONGRESS