Fetal thyroid function

Rodesch F, Camns M, Ermans AM, Dodion J, Delange F. Amniofoetographie et fonction thyroidienne foetale. [Adverse effect of amniofetography on fetal thyroid function.] Ann Endocrinol (Paris) 1978 39(2) 145-6. 

Fisher DA. Fetal thyroid function Diagnosis and management of fetal thyroid disorders. Chn Obstet Gynecol 1997 40 16-31. 

G. N. Burrow, D. A. Fisher, and R R. Larsen Mechanisms of disease maternal and fetal thyroid function. New England Journal of Medicine 331, 1072 (1994). 

Although fetal thyroid function does not commence until the equivalent of 12 weeks gestation in man, the presence of functional fetal nuclear receptors for T3 is noted in early pregnancy, indicating that triiodothyronine is exerting an action at this time (De Nayer and Dozin, 1989). 

Six women (10%) were TPO-Ab (-E) with values ranging from 1890 to 607U/ml. No repercussion on their own or the fetal thyroid function was detected. There were no significant differences between UIE or serum fT4 between smokers and nonsmokers. 

After the onset of fetal thyroid function, there is a clear increase in the fetal pools of T4 and T3 in the rat thyroid, and T4 increases about 10-fold in fetal plasma and tissues (Ruiz de Ona et al., 1991). Plasma T3 is very low during fetal life, but the generation ofT3 in the fetal tissues is variable depending on the ontogenic development of deiodinases in each tissue (Ruiz de Ona et al, 1991). 

T4 and T3 is very low and the extrathyroidal pools are also low (Obregon et al, 1991). Fetal brain T4 is low and T3 in fetal brain keeps at very low levels (Figure 64.3) after the onset of fetal thyroid function, despite the large increase of D2 in the fetal brain (Obregon et al, 1991). 

Figure 64.3 Concentrations of T4, T3 and D2 activity in the brain of rat fetuses (left side) between the onset of fetal thyroid function (18dg) and birth (B) and in litters from pups until 4 weeks of postnatal age (right side) born from mothers on an iodine-deficient (LID) and iodine-supplemented (LID -H I) diet. Data (mean SEM) are from Obregon etal., (1991).

Development of the neocortex can be affected by short periods of maternal hypothyroxinemia, before the onset of fetal thyroid function. Therefore, to maintain normal thyroxinemia in the mother is of maximal importance to maintain normal T3 levels in the fetal brain. 

Prior to the onset of fetal thyroid function, namely by 6 weeks of gestation, T4 has been proven to be measurable in all fetal fluids and in concentrations that correlate... 

Thyroid hormones, T3 and T4, have been i cwn to play significant but poorly understood roles in development and differentiation of rodent and human brain (1-7). In the human, disorders of maternal and fetal thyroid function include maternal and secondary fetal iodine deficiency, maternal hypothyroidism or hyperthyroidism, as well eis disorders related to deficient fetal autcxiomous thyroid hormcaie secretion, i.e., goiter or i radic oongenitel hypothyroidism. These disorders are identifiable causes of mental retardation (4, 8, 9, 10), cer ral peilsy (11, 12), and other significant neurological abnormalities (5, 6, 11) ... 

These observations suggested that normal brain development requires the availability of both maternal and fetal thyroid hormones,a suggestion which is at variance with earlier reports (9) (14) (15) (16) that the placenta in many mammalian species is relatively impermeable to thyroid hormones and with the suggestion (17) (18) that early mammalian development takes place normally in the absence of thyroid homrones. The observations do agree however with a more recent report (19) that rat embryonic tissues are provided with T and T3 only four days after uterine implantation and well before the onset of fetal thyroid function at 17 days. y also supported by the work of Woods et al (20) who showed that T and T3, when injected into pregnant rats, entered the rat... 

Potter et al (21) extended and confirmed their earlier observations and were able to show that surgical thyroidectomy of ewes 6 weeks prior to conception caused a reduction in fetal brain and body growth in mid-gestation compared to that of fetuses from sham-operated ewes. The differences were no longer evident in the neonatal brain at parturition after the onset of fetal thyroid function but the possibility of residual damage remains to be explored with behavioural and functional studies of brain function. 

The data reviewed reveal significant effects on fetal brain development. The study of the mechanisms in the sheep reveals the role of both maternal and fetal thyroid function. 

Rey, F. Effects of maternal hypothyroidism on weight and thyroid hormone content of rat embryonic tissues,before and after onset of fetal thyroid function. Endocrinology 117 1890-1900 (1985). 

THYROID HORMONES IN EMBRYONIC TISSUES BEFORE ONSET OF FETAL THYROID FUNCTION... 

Work performed by Weiss and Novak 5 and by Sweney and Shapiroi strongly suggested the possibility that maternal thyroid hormones are available to the rat embryo before onset of fetal thyroid function, despite opinions to the contrary 1 . We decided to re-investigate this possibility by measuring T4 and T3 concentrations in embryonic and fetal tissues. We had developed specific and sensitive RIAs 18, and extensive extraction and purification... 

With this dating, birth occurs at 22.7 0.2 (SEM) gd. As summarized in Fig 1 A, all tissues obtained from the fetal compartment before onset of fetal thyroid function contained T4 and T3 9. They were found in molar ratios which were quite different from those of maternal plasma, thus excluding contamination with maternal blood. These results were in agreement with the simultaneous independent study by Woods et al. showing transfer from mother to embryos of labeled iodothyronines early in gestation. 

Studies by P rez-Castillo et al.26 have shown the presence of nuclear receptors for T3 in rat embryos as early as 13 gd, in brain by 14 gd, and in liver, heart and lung from 15 gd onwards (Figure 2 B). Therefore, both the hormone and its receptor are present before onset of fetal thyroid function, and it does not appear far-fetched to suggest that a biological effect might ensue, though this possibility has not yet been confirmed nor the possible effect defined. 

Table 1 outlines the experimental design which we used. Methimazole (MMI) was used to block maternal and fetal thyroid function. Some of the MMI-treated dams received a replacement dose of T4 given by constant infusion, as described in detail elsewhere23. The main findings are summarized in Fig. 5, which shows the T4 and T3 concentrations in fetal carcass and brain. Comparison of the hormone levels in fetuses from C + MMI + T4 (or T + MMI + T4) dams with those from C + MMI (or T + MMI) mothers shows that infusion of T4 into the mothers not only ameliorates fetal deficiency of T4, but also of T3. This occurs without an increase of fetal plasma T3, suggesting that the fetal brain derived its T3 from local deiodination of T4. 

Embryonic and fetal samples were obtained before (at 11 and 17 gd ) and after (21 gd ) onset of fetal thyroid function L Maternal plasma T4 was very low in the LID dams, and could only be measured after extraction of larger samples than used for the direct RIA. T3 levels were similar to those of LID + I dams, and decreased in both groups at the end of pregnancy. 

The LID fetuses developed goiter, and their thyroidal total iodine was 4.7 % of that of LID + I fetuses. The concentrations of T4 and T3 in different embryonic and fetal samples are shown in Figs. 8 and 9, where they are compared to data from age-paired samples obtained from C and T dams. Before onset of fetal thyroid function (11-day-old embryotrophoblasts and 17-day old fetuses) T4 concentrations are decreased by LID to a degree comparable to that of concepta taken from T mothers. T3 concentrations did not differ initially from those of the LID + I group. By 17 gd, however, T3 concentrations were lower both in the fetus, and placenta (not shown). Once fetal thyroid function starts, important differences become apparent between fetuses from T and LID dams. The activated secretion of T4 and T3 by the thyroid in fetuses from T mothers is able to compensate for previous differences related to maternal hypothyroidism, at least as far as the brain is concerned. But this is not possible for fetuses faced with a very low iodine supply, and cerebral T3 is quite low. Similar results were later obtained in another experimental series ... 

Obregdn MJ, Mallol J, Pastor R, Morreale de Escobar G, Escobar del Rey F, Thyroxine and triiodothyronine in rat embryos before onset of fetal thyroid function. Endocrinology 114 305 (1984)... 

In the human, the concentration of reverse T3 (rT3), an iodothyronine generated from 5-deiodination of T4, in amniotic fluid (AF) far exceeds its concentration in maternal serum. Rat models of fetal hypothyroidism, maternal hypothyroidism and combined maternal-fetal hypothyroidism were enoployed to explore the source (s) of AF rT3 since it had earlier been suggested that AF rT3 concentration mi t be used as a means of diagnosing fetal hypothyroidism in utero. These studies indicated that AF rT3 content was influenced by maternal and not fetal thyroid function (Table 1) and that rT3 itself was poorly trani rted from maternal serum into the amniotic cavity. Fetal serum rT3 concentration is dependent ipon both maternal and fetal thyroid function. Suzuki et al., have also r rted that changes in rat AF rT3 concentration are mainly dependent ipon maternal thyroid function. These findings suggested to us that tissues in contact with both maternal serum and fetal serum, or maternal tissues and the... 

In addition, data collected in rats showed that maternal hypothyroxinemia results in fetal hypothyroxinemia and brain damage during early pregnancy, even before the onset of fetal thyroid function (75-81). 

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