Maternal Thyroid Function is the Major Determinant of Amniotic Fluid 3,3′,5′-Triiodothyronine in the Rat

Abstract

3,3′,5′-triiodothyronine, (rT₃), is easily measured in human amniotic fluid (AF) during the second and third trimesters. To determine if AF rT₃ levels are maintained by either maternal or fetal thyroid function, or both, models of fetal hypothyroidism (FH), maternal hypothyroidism (MH), and combined maternal and fetal hypothyroidism (MFH) were developed in pregnant rats. Hormone analyses of maternal and fetal serum and AF were performed at term. Thyroxine (T₄) and 3,3′,5-triiodothyronine (T₃) were not detectable in the sera and AF of term fetuses in all groups. MFH rats were prepared by administration of methimazole to the dams, and in some experiments, by maternal thyroidectomy and a low iodine diet as well. In the MFH groups from the three experiments serum thyrotropin (TSH) was markedly elevated in the dams and in the fetuses. FH rats were prepared by administering T₄ by various routes to dams treated according to the MFH protocols and serum TSH was elevated in fetal serum. Analysis of FH maternal serum T₄, T₃, and TSH concentrations suggested mild maternal hyperthyroidism or hypothyroidism depending upon the schedule of T₄ administration. The MH groups were prepared by maternal thyroidectomy and in all experiments the fetuses had normal serum TSH concentrations. The degree of maternal hypothyroidism in the MH and MFH groups was equivalent. The mean concentration of AF rT₃ in normal rats in three experiments was 28.4±2.5 ng/dl (±SEM). In the three experiments, AF rT₃ was undetectable or markedly reduced in the MH and MFH rats and was normal in the FH rats. These results in the amniotic fluid could not be explained by transfer of rT₃ from fetal serum to the AF because fetal serum rT₃ concentrations in these various models did not correlate with AF rT₃ concentration. Furthermore, infusion of large doses of rT₃ in MFH dams resulted in a 35-fold elevation in maternal serum rT₃ concentration, a twofold elevation in fetal serum rT₃ concentration, and only a minimal increase in AF rT₃. These studies demonstrated that, in the rat, the maternal thyroid has the dominant role in maintaining AF rT₃, whereas little effect of fetal thyroid status on AF rT₃ could be demonstrated. Transfer of maternal rT₃ or of fetal rT₃ derived from maternal T₄ to the AF do not appear to be the mechanisms whereby the maternal thyroid maintains AF rT₃.