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 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.
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