Background: Maternal thyroid hormones are necessary for the growth of the central nervous system before birth and their shortage can delay cerebellum development.
Aim: This study aimed to evaluate the effect of maternal hypothyroidism induction on the development of the cerebellar cortex postnatally in offspring and to compare thyroxin replacement to mothers and postnatally to offspring.
Material and Methods: Rat offspring were divided into 3 groups; group I (control), group II (hypothyroid); 15 offspring whose mothers received carbimazole (20 mg/kg/day orally) from the 1st gestational day to the 21st day of lactation. Group III (thyroid hormone replacement) included subgroup IIIa (15 rats) their mothers received carbimazole as group II and Levothyroxine (20 μg/kg/day subcutaneously) from the 10th day of gestation to 21st day of lactation, and subgroup IIIb (15 rats), their mothers received carbimazole as group II and offspring received Levothyroxine (20μg/kg/day subcutaneously) from day 1 postnatally. At the end of 1st, 2nd, and 3rd postnatal weeks, serum Thyroid-stimulating hormone, Free triiodothyronine, and thyroxin were estimated. Cerebellar cortex sections were stained with hematoxylin and eosin, Neurofilament, Myelin basic protein, and Bcl2 immunohistochemical stains. The real-time polymerase chain reaction was done for the reelin gene.
Results: Group II showed a significantly reduced Free triiodothyronine, thyroxin, and increased Thyroid-stimulating hormone. Vacuolation in the external granular layer and delayed its disappearance and degeneration of Purkinje cells that increased with age were observed. Reduced myelination, neurofilament content, and Reelin gene expression in the offspring were also detected. Replacement therapy (group III) especially to the mothers (subgroup IIIa) revealed amelioration of these changes.
Conclusion: Maternal hypothyroidism impaired development of the offspring cerebellar cortex. However, thyroxin replacement for mothers was more effective than the treatment of offspring. Therefore, treatment of hypothyroid mothers during pregnancy is essential to ensure adequate cerebellar cortex development.