During gestation the normal function of the maternal-fetal unit is crucial since it is the cornerstone for the physiological development of the fetus. Ultrasound-guided amniocentesis and cordocentesis have given researchers a greater insight into the mechanisms of maternal-fetal transfer of T4 and T3 which is crucial for normal brain physiology of the fetus. The human fetus is surrounded by two distinct fluid cavities for most of the first trimester: the inner (amniotic) cavity contains the fetus, and the outer (exocoelomic) cavity separates the amniotic cavity from the placenta and contains the secondary yolk sac (fig. 1a). The exocoelomic cavity is the site of important molecular exchanges between the mother and the fetus [28-30]. The coelomic fluid results from an ultrafiltrate of maternal serum with specific placental and secondary yolk sac bioproducts . It has been shown that T4 (and possibly T3) is present in colelomic fluid as early as 5.6 weeks' gestation [29, 31]. Maternal T4 is transferred into the exocoelomic cavity and subsequently into the fetal gut and circulation via the secondary yolk sac. The second mode of transfer of maternal nutrients starts at the end of the first trimester. The secondary yolk sac and 2/3 of the placental mass degenerate, and the amniotic cavity containing the fetus
grows and obliterates the exocoelomic cavity (fig. 1b) considerably changing the maternal-fetal exchange pathways. From the 11 to 12th weeks of gestation and onward, maternal nutrients, including thyroid hormone, are transferred by the placenta directly into the fetal circulation.
The placenta plays an important role in the development and function of the thyroid gland in the fetus. The placenta produces various hormones that can influence the fetal thyroid gland (e.g. chorionic gonadotropin, TRH). The most important role of the placenta though is in regulating the passage of hormones and drugs, from the mother to the embryo, which influence the fetal thyroid gland. For many years its was unknown how the very small amounts of maternal T4 which are allowed to pass the placental barrier (sometimes as low as 1% of the maternal concentrations in the first trimester) can play such a major role in the normal fetal physiology of the developing brain and fetal tissues. The answer came from studies which showed that fetal concentrations of total T4 were misleading because the proportion of T4 that is not bound to proteins
(FT4) is much higher than in adult sera and the concentrations of T4 that are available to developing tissues reach values that are comparable to those know to be biologically active in their mothers [28, 29] (fig. 2). The T4-binding proteins and the concentrations of maternal T4 or FT4 that are allowed to pass the placental barrier determine the concentrations of FT4 in the fetal fluids and this is determined ontogenically. Therefore, it has become clear why an efficient barrier to complete maternal thyroid hormone transfer is necessary as the same concentrations that are available in the maternal sera might possibly be toxic to the developing fetal tissues [22, 30]. However, if the fetus is hypothyroid the placenta allows T4 from the mother to pass to the fetus in larger quantities .
In contrast to what happens with thyroid hormones the placenta allows the free passage of TRH and iodine from the mother to the fetus. As mentioned previously, if there is iodine insufficiency in the mother the neonate may develop severe psychomotor retardation [23-27]. Furthermore, the placenta allows the passage of certain drugs (propylthiouracil and methimazole) and immunoglobulins (like TSH-receptor-stimulating antibodies) from the mother to the fetus which can influence the function of the thyroid gland of the fetus and the neonate.
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