Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta

The influence of maternal hypothyroxinemia on the expression of the glucose transporters, GLUT1 and GLUT3, in rat fetal brain and placenta was investi gated. Fetal growth was retarded in hypothyroxinemic pregnancies, but only before the onset of fetal thyroid hormone synthesis. Placental weights were normal, but placental total protein concentration was reduced at 19 days g estation (dg). Immunoblotting revealed a decreased abundance of GLUT1 in pl acental microsomes at 16 dg, whereas GLUT3 was increased. Fetal serum gluco se levels were reduced at 16 dg. In fetal brain, the concentration of micro somal protein was deficient at 16 dg and the abundance of parenchymal forms of GLUT1 was further depressed, whereas GLUT3 was unaffected. Northern hyb ridization analysis demonstrated normal GLUT1 mRNA levels in placenta and f etal brain. In conclusion, maternal hypothyroxinemia results in fetal growth retardatio n and impaired brain development before the onset of fetal thyroid function . Glucose uptake in fetal brain parenchyma may be compromised directly, due to deficient GLUT1 expression in this tissue, and indirectly, as a result of reduced placental GLUT1 expression. Though corrected by the onset of fet al thyroid hormone synthesis, these deficits are present during the critica l period of neuroblast proliferation and may contribute to long term change s in brain development and function seen In this model and in the progeny o f hypothyroxinemic women.