Abstract

Synthesis of thyroid hormones, thyroxine(T-4) and tri-iodothyronine(T-3), 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 T-4 during first trimester of pregnancy, suggesting that T-4 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 T-3/T-4 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 T-3/T-4 in the feto-placental circulation, and therefore may generate an adaptive response in cases where the mother courses with low levels of T-4. In addition, T-3/T-4 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 otherhand, low levels of T-4 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 T-4 level at the maternal circulation could result in analtered 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 T-4 observed in GD may be compensated by increased placental availability of T-3/T-4 via elevation in the activity of THT and/or reduction in deiodinases in the feto-placental circulation.