Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: I. The development of the thyroid hormones–neurotransmitters and adenosinergic system interactions

O.M. Ahmed, S.M. Abd El-Tawab, R.G. Ahmed
  • International Journal of Developmental Neuroscience, October 2010, Elsevier
  • DOI: 10.1016/j.ijdevneu.2010.06.007

Thyroid disorders, neurotransmitters and adenosinergic system interactions

What is it about?

The adequate functioning of the maternal thyroid gland plays an important role to ensure that the offspring develop normally. Thus, maternal hypo- and hyperthyroidism are used from the gestation day 1 to lactation day 21, in general, to recognize the alleged association of offspring abnormalities associated with the different thyroid status. In maternal rats during pregnancy and lactation, hypothyroidism in one group was performed by antithyroid drug, methimazole (MMI) that was added in drinking water at concentration 0.02% and hyperthyroidism in the other group was induced by exogenous thyroxine (T4) (from 50g to 200g/kg body weight) intragastric administration beside adding 0.002% T4 to the drinking water. The hypothyroid and hyperthyroid states in mothers during pregnancy and lactation periods were confirmed by measuring total thyroxine (TT4) and triiodothyronine (TT3) at gestational day 10 and 10 days post-partum, respectively; the effect was more pronounced at the later period than the first. In offspring of control maternal rats, the free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations were pronouncedly increased as the age progressed from 1 to 3 weeks. In hypothyroid group, a marked decrease in serum FT3, FT4 and GH levels was observed while there was a significant increase in TSH level with age progress as compared with the corresponding control. The reverse pattern to latter state was recorded in hyperthyroid group. The thyroid gland of offspring of hypothyroid group, exhibited some histopathological changes as luminal obliteration of follicles, hyperplasia, fibroblastic proliferation and some degenerative changes throughout the experimental period. The offspring of hyperthyroid rats showed larger and less thyroid follicles with flattened cell lining epithelium, decreased thyroid gland size and some degenerative changes along the experimental period. On the other hand, the biochemical data revealed that in control offspring, the levels of iodothyronine 5-monodeiodinase (5-DI), monoamines, -aminobutyric acid (GABA), acetylcholinesterase (AchE), ATPase-enzymes (Na+,K+-ATPase, Ca2+-ATPase and Mg2+-ATPase) follow a synchronized course of development in all investigated brain regions (cerebrum, cerebellum and medulla oblongata). In addition, the depression in 5-DI activity, monoamines levels with age progress in all investigated regions, was more pronounced in hypothyroid offspring, while they were increased significantly in hyperthyroid ones in comparison with their respective controls. Conversely, the reverse pattern was recorded in level of the inhibitory transmitter, GABA while there was a disturbance in AchE and ATPases activities in both treated groups along the experimental period in all studied regions. In conclusion, the hypothyroid status during pregnancy and lactation produced inhibitory effects on monoamines, AchE and ATPases and excitatory actions on GABA in different brain regions of the offspring while the hyperthyroid state induced a reverse effect. Thus, the maternal hypothyroidism and hyperthyroidism may cause a number of biochemical disturbances in different brain regions of their offspring and may lead to a pathophysiological state. These alterations were age dependent.

Why is it important?

In conclusion, the methimazole-induced hypothyroidism and exogenous T4-induced hyperthyroidism in rat dams affect the serum THs level and thyroid gland histological architecture of their offspring. The maternal hypothyroidism induced decreases in monoamine levels as well as AchE activity and increase in GABA content concomitant with suppression of Na+,K+-ATPase, Ca2+-ATPase, Mg2+-ATPase activity in different brain regions of the offspring. The maternal hyperthyroidism produced reverse effects in offspring. Thus, the maternal hypothyroidism and hyperthyroidism may respectively induce inhibitory and stimulatory effects on the excitability and synaptic neurotransmissions in cerebrum, cerebellum and medulla oblongata of their offspring.


Ahmed R. G. (Author)
Division of Anatomy and Embryology, Zoology department, Faculty of Science, Beni-Suef University, Egypt.

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The following have contributed to this page: Ahmed R. G. and Prof. Dr. Osama M Ahmed