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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