Ontogenesis of thyroid function and interactions with maternal function.
Fetal and neonatal development of thyroid function involves the embryogenesis, differentiation and maturation of the thyroid gland, of the hypothalamic-pituitary-thyroid axis and of the systems controlling thyroid hormone metabolism. We focus here on aspects related to neurodevelopment. Throughout gestation, thyroxine (T4) transferred from the mother, present in embryonic fluids by 4 weeks, protects the fetal brain. Free T4 (FT4) in fetal fluids increases rapidly, approaching adult levels by midgestation, in concentrations that are determined by the maternal serum T4. T3 remains very low throughout pregnancy. In the cerebral cortex T3, generated from T4, reaches adult values by midgestation and is partly bound to specific nuclear receptor isoforms. The iodothyronine deiodinases are important for the spatial and temporal presence of T3 in different fetal brain areas. After onset of fetal thyroid secretion at midgestation, maternal transfer of T4 continues to contribute importantly to fetal serum T4, protecting neurodevelopment until birth. In rats, even a transient period of maternal hypothyroxinemia disrupts neurodevelopment irreversibly, supporting epidemiological evidence for its negative role in human neurodevelopment. The prompt treatment of maternal hypothyroidism or hypothyroxinemia should mitigate negative effects on neurodevelopment. Neurodevelopmental deficits of preterm infants might also result from an untimely interruption of the maternal transfer of T4 [Morreale de Escobar et al: J Clin Endocrinol Metab 2000;85:3975-3987; Best Pract Res Clin Endocrinol Metab 2004;18:225-248; Eur J Endocrinol 2004;151(suppl 3):U25-U37].
Instituto de Investigaciones Biomedicas, Centro mixto 'Alberto Sols' (CSIC-UAM), Madrid, Spain.
M J
MJ
Obregon
R M
RM
Calvo
F
F
Escobar Del Rey
G
G
Morreale de Escobar
D000818:Animals; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology; D008431:Maternal-Fetal Exchange / Q000502:physiology; D011247:Pregnancy / Q000378:metabolism / Q000502:physiology*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D013961:Thyroid Gland / Q000196:embryology*; D013963:Thyroid Hormones / Q000502:physiology
D013963:Thyroid Hormones