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Developmental Hypothyroxinaemia Induced by Maternal Mild Iodine Deficiency Delays Hippocampal Axonal Growth in the Rat Offspring
Author(s) -
Wei W.,
Wang Y.,
Wang Y.,
Dong J.,
Min H.,
Song B.,
Teng W.,
Xi Q.,
Chen J.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12058
Subject(s) - offspring , hippocampal formation , endocrinology , medicine , iodine deficiency , hormone , triiodothyronine , biology , thyroid , fetus , pregnancy , genetics
Iodine is essential for the biosynthesis of thyroid hormones, including triiodothyronine and thyroxine. Thyroid hormones are important for central nervous system development. Mild maternal iodine deficiency ( ID )‐induced hypothyroxinaemia causes neurological deficits and mental retardation of the foetus. However, the detailed mechanism underlying these deficits is still largely unknown. Given that the growth‐associated protein of 43 kDa ( GAP ‐43), s emaphorin 3 A (Sema3 A ) and the glycogen synthase kinase 3β ( GSK 3β)/collapsin response mediator protein 2 ( CRMP 2) pathway are essential for axonal development, we hypothesise that hippocampal axonal growth‐related proteins may be impaired, which may contribute to hippocampal axonal growth delay in rat offspring exposed to maternal hypothyroxinaemia. To test this hypothesis, maternal hypothyroxinaemia models were established in W istar rats using a mild ID diet. Besides a negative control group, two maternal hypothyroidism models were created with either a severe ID diet or methimazole in the water. Our results showed that maternal hypothyroxinaemia exposure delayed offspring axonal growth on gestational day 19, postnatal day ( PN ) 7, PN 14 and PN 21. Consistent with this, the mean intensity of hippocampal CRMP 2 and T au1 immunofluorescence axonal protein was reduced in the mild ID group. Moreover, maternal hypothyroxinaemia disrupted expressions of GAP ‐43 and Sema3 A . Furthermore, the phosphorylation of GSK 3β and CRMP 2 was also affected in the treated offspring, implying a potential mechanism by which hypothyroxinaemia‐exposure affects neurodevelopment. Taken together, our data support the hypothesis that maternal hypothyroxinaemia may impair axonal growth of the offspring.