Abstract
Synthesis of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3), in the human fetus starts from 17 to 19th weeks of gestation. Despite the majority of normal pregnant women reaching adequate levels of circulating thyroid hormones, in some cases, women with normal pregnancies have low level of free T4 during first trimester of pregnancy, suggesting that T4 action may be compromised in those women and their fetuses. In addition, pathological low levels of thyroid hormones are detected in isolated maternal hypothyroxemia (IMH) and clinical hypothyroidism. Nevertheless, human placenta regulates T3/T4 concentration in the fetal circulation by modulating the expression and activity of both thyroid hormone transporters (THT) and deiodinases. Then, placenta can control the availability of T3/T4 in the feto-placental circulation, and therefore may generate an adaptive response in cases where the mother courses with low levels of T4. In addition, T3/T4 might control vascular response in the placenta, in particularly endothelial cells may induce the synthesis and release of vasodilators such as nitric oxide (NO) or vasoconstrictors such as endothelin-1 mediated by these hormones. On the other hand, low levels of T4 have been associated with increase in gestational diabetes (GD) markers. Since GD is associated with impaired placental vascular function characterized by increased NO synthesis in placental arteries and veins, as well as elevated placental angiogenesis, it is unknown whether reduced T4 level at the maternal circulation could result in an altered placental endothelial function during GD. In this review, we analyze available information regarding thyroid hormones and endothelial dysfunction in GD; and propose that low maternal levels of T4 observed in GD may be compensated by increased placental availability of T3/T4 via elevation in the activity of THT and/or reduction in deiodinases in the feto-placental circulation.
Highlights
Thyroid gland produces tetra-iodothyronine (T4 or thyroxine) and tri-iodothyronine (T3)
We propose that low levels of T4, lead to an increase in the number and activity of thyroid hormone transporters (THT) membrane transporters available at the plasma membrane of the human placental endothelial cells, and reduced deiodinase expression and activity, in order to supply T4 necessities associated with fetal development in gestational diabetes (GD)
FINAL COMMENTS AND CONCLUSION Based on what was described in this review, our central research questions are: (1) is a low level of free T4 in the maternal circulation associated with GD? (2) is GD a disease associated with increased placental THT, but reduced deiodinase expression and activity? and (3) would the potential changes caused by reduced free T4 level in the maternal circulation and altered THT and deiodinases in the placenta in GD lead to placental endothelial dysfunction? nothing is known regarding the feto-placental vascular function/dysfunction in pregnancies where the mother courses with hypothyroxemia
Summary
Thyroid gland produces tetra-iodothyronine (T4 or thyroxine) and tri-iodothyronine (T3). It has been described that ∼35 or ∼3% of women with an apparent normal pregnancy have clinical hypothyroidism or exhibit maternal hypothyroxemia (low level of free T4), respectively (Mosso et al, 2012), both maternal conditions associated with several alterations in the fetus development (Parkes et al, 2012).
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