Different response to maternal hypothyroidism during the first and second half of gestation in the rat.

Female rats were mated and thyroidectomized (T) on the same day and divided into four groups. Three groups were subsequently treated daily with 1.8 micrograms L-T4/100 g body wt: 1) for the first 12 days [T + T4 (I)]; 2) from the 12th day until death [T + T4 (II)]; or 3) for the entire 21-day study [T + T4 (I + II)]. The other T animals were maintained without treatment. (T), and another group of mated rats were sham operated (C). Maternal body weight increase during gestation did not differ between T + T4 (I + II) and C dams, whereas it was smaller in T dams from the 7th gestational day onward. Neither interruption of T4 treatment in the T + T4 (I) rats after the 12th day nor treatment initiated at that time in the T + T4 (II) group modified their body weights. At day 21, the weights of the maternal conceptus-free body and liver, the placenta, and the fetuses were lower in the T and T + T4 (II) animals than in either the C and the T + T4 (I + II) animals. Maternal plasma T4 and pituitary GH content were reduced, and plasma TSH was enhanced in both T and T + T4 (I) dams. In fetuses, plasma TSH concentration was augmented in T and T + T4 (I) rats and unchanged in T + T4 (II) animals when compared with those of T + T4 (I + II). Pituitary GH content was reduced in T and T + T4 (II) fetuses and unchanged in the T + T4 (I) group. We propose that maternal thyroidectomy greatly decreases the thyroid hormone levels in embryonic structures during the first half of gestation and inhibits normal maternal metabolic changes during this period. In addition to interfering with normal fetal development, these effects reduce the quantity of maternal substrates available to fetuses during the last phase of gestation. In contrast, when maternal hypothyroidism occurs during the second half of gestation, the effects are not as detrimental because fetal thyroid gland activity is adequate, and maternal catabolic adaptations are not impaired.