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

Abstract

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 50 microg to 200 microg/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, gamma-aminobutyric acid (GABA), acetylcholinesterase (AchE), ATPase-enzymes (Na(+),K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-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 hypert...

The Effects of Maternal Hyperthyroidism on Histologic Changes in Parietal Lobe in Rat Embryos

“…This issue was also observed in rodents, i.e. the impact of the thyroid hormone on the trend of evolution of the cerebellum by two weeks after birth [20]. If the thyroid hormones do not discharge sufficiently in the embryonic period, the natural evolution of the cerebellum will face difficulty [25,26].These results are in agreement with the findings of the current study.…”

“…T3, after its transfer into the embryonic brain or the removal of iodine from it. If the rate of these hormones is at a natural level, the embryo develops naturally; a decrease or increase in the rate of thyroid hormones of the mother can be a factor of disruption of growth in embryos [19,20]. The fluctuations related to each hormone can intensively influence the mechanism of body chemical interactions [21].…”

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

“…In cerebellar cell cultures, dendritic growth of Purkinje cells was significant in the presence of T3 or T4, but not in the absence of thyroid hormones (3,4). In rats, studies have demonstrated the structural and functional consequences of maternal thyroid dysfunction on the fetal brain including alterations in the neuronal proliferation, migration, differentiation, synaptogenesis and myelination (1,2,5).…”

Gestational Prooxidant-Antioxidant Imbalance may be at Higher Risk for Postpartum Thyroid Disease

“…Any reduction in the availability of THs might possibly disturb the fetal and neonatal development [1][2][3][4][5][6][7][8][9][10][24][25][26]. These imbalances resulting from the production of free radicals, lipid peroxidation (LPO), carbonylation and nitration, and reduce the enzymatic and non-enzymatic antioxidant defense system [2,5,6,[33][34][35].…”