Fetal-to-Maternal Transfer of Thyroid Hormone Metabolites in Late Gestation in Sheep

Abstract

3,3'-Diiodothyronine sulfate (T2S) derived from T3 of fetal origin is transferred to the maternal circulation and contributes significantly to the maternal urinary pool. The present study quantitatively assesses the fetal to maternal transfer of T4 metabolites compared with those of T3. Labeled T4 or T3 was infused intravenously to four singleton fetuses in utero in each group at gestational age 138 +/- 3 d. Maternal and fetal serum and maternal urine samples were collected hourly for 4 h and at 24 h (serum) or in pooled 4-24 h samples (urine). Radioactive metabolites were identified by HPLC and by specific antibody in serum and urine extracts and expressed as percentage infusion dose per liter. The results demonstrate a rapid clearance of labeled T3 from fetal serum (disappearance T(1/2) of 0.7 h versus 2.4 h for T4 in the first 4 h). The metabolites found in fetal serum after labeled T3 infusion were T2S > T3 > T3S; in maternal urine, T2S > unconjugated iodothyronines (UI) > T3S > unknown metabolite (UM). After labeled T4 infusion, the metabolites in fetal serum were rT3 > T3 > T2S > T4S in the first 4 h, and rT3 = T3 = T4S = T2S > T3S at 24 h; in maternal urine we found T2S > UM > UI > T4S > T3S in the first 4 h and UM > T2S > UI in 4-24 h pooled sample. In conclusion, the conversion of T3 to T2S followed by fetal to maternal transfer of T2S and other iodothyronines appears to contribute importantly to maintaining low fetal T3 levels in late gestation.