10th 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

10th 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

10th AOTA CONGRESS

Background

Th

yro

id d

isea

se

s

< 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

10th AOTA CONGRESS

BackgroundOur previous study

Excessive iodine intake could increase the risk of subclinical hypothyroidism in offspring

Chin Med J (Engl) 2004, 117(10):1518-1522

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Our previous study

Thyroid 2010, 20(8):909–915

Maternal overt and subclinical hypothyroidism affect the expression of BDNF

Background

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Neurotoxicology 2012, 33(4):842-852

 Neurotoxicology 2005, 26(3):417-426

Neurotoxicol Teratol 2011, 33(4):464-472

G17 PN7 PN45

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

10th AOTA CONGRESS

Whether higher-than-normal iodine intake

from before pregnancy until breastfeeding

affects the postnatal neurodevelopment and

cognitive function

Objective

10th AOTA CONGRESS

SPF female Wistar rats 80-120 g (n = 60)

normal iodine (n=20)

(NI, 140 μg /L KIO3)

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

10th 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

10th AOTA CONGRESS

Results

Urinary and thyroidal iodine content

*P < 0.05 compared with normal iodine control group

Urinary iodine concentration (μg/L)

0

200

400

600

800

*

*

Thyroidal iodine concentration (μg/L)

0

200

400

600

800

LINI3HI

*

*

10th AOTA CONGRESS

Maternal thyroid hormone

*P < 0.05 compared with normal iodine control group

Results

TSH (mIU/L)

00. 10. 20. 30. 40. 50. 60. 70. 80. 9

11. 11. 21. 31. 4

pre-pregnancy G17

LI

NI

3HI

*

*

TT4 (μg/dL)

0

1

2

3

4

5

6

7

pre-pregnancy G17

*

*

* *

FT4 (pmol/L)

0

5

10

15

20

25

30

35

pre-pregnancy G17

*

*

*

10th AOTA CONGRESS

*P < 0.05 compared with normal iodine control group

Pup thyroid hormone

Results

FT4 (pmol/L)

05

10152025303540

PN7 PN45

*

*

TSH (mIU/L)

00. 050. 1

0. 150. 2

0. 250. 3

0. 350. 4

PN7 PN45

LI

NI

3HI

*

*

*

TT4 (μg/dL)

0

1

2

3

4

5

6

PN7 PN45

**

10th AOTA CONGRESS

Effect of 3HI on the protein expressions of c–Fos and c-Jun in the CA1 area of hippocampus

Results

c-jun IOD Value (103)

0

2

4

6

8

10

12

14

PN7 PN45

LINI3HI

**

c-fos IOD Value (103)

0

2

4

6

8

10

12

14

PN7 PN45

LI

NI

3HI

* *

*P < 0.05 compared with normal iodine control group

10th AOTA CONGRESS

Effect of 3HI on BDNF and NSP-A expression in the hippocampus

Results

NSP-A immunoreactivity (Ratio to β-actin)

0

0. 2

0. 4

0. 6

0. 8

1

1. 2

1. 4

PN7 PN45

LI

NI

3HI

#

#

*

BDNF immunoreactivity (Ratio to β-actin)

0

0. 2

0. 4

0. 6

0. 8

1

1. 2

PN7 PN45

LI

NI

3HI

# #

**

# P < 0.01 compared with the NI group on the same day; * P < 0.05 compared with the NI group on the same day

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# 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

20

40

60

80

100

120

140

1 2 3 4 5

Training Days

Esc

ape

Lat

ency

(s)

LINI3HI

*

#

#

#

*

*

10th 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

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