Thyroid hormones: Metabolism and transportation in the fetoplacental unit

Abstract

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are of vital importance for fetal development. The concentration of THs in fetal circulation varies throughout gestation and differs from the concentration in the maternal serum, indicating the presence of maternal‐fetal thyroid homeostasis regulatory mechanisms in the placenta. The passage of THs from maternal circulation to fetal circulation is modulated by plasma membrane transporters, enzymes, and carrier proteins. Monocarboxylate transporter 8, iodothyronine deiodinases (DIO2 and DIO3), and transthyretin are especially involved in this maternal‐fetal thyroid modulation, shown by a greater expression in the placenta. THs also play a role in placental development and as expected, abnormal variations in TH levels are associated with pregnancy complications and can result in damage to the fetus. Although new evidence regarding TH regulation during pregnancy and its effects in the mother, placenta, and fetus has been published, many aspects of these interactions are still poorly understood. The objective of this review is to provide an evidence‐based update, drawn from current data, on the metabolism and transport of THs in the placenta and their vital role in the maternal‐fetal relationship.

Association between maternal age and sex-based neonatal free triiodothyronine levels

“…DIO3 catalyzes the inactivation of T4 to rT3 and of T3 to diiodothyronine (T2), decreasing the levels of T4 and T3. [ 20 , 21 ]. Changes in the expression and activity of DIOs, manifesting as a decrease in DIO2 and an increase in DIO3, under hypoxia and oxidative stress have been described.…”

Iodine and Thyroid Maternal and Fetal Metabolism during Pregnancy

“…Their presence in human choriocarcinoma cell lines has been known for over 30 years [ 92 ]. More than 15 TH transporters have been identified, but only a fraction of those are involved in placental traffic [ 93 , 94 ]. mRNA sequencing of human placentas showed that L-type Amino-acid Transporters (LAT1 and LAT2), Mono-Carboxylate Transporters (MCT8 and MCT10), and Organic-Anion Transporting Peptides (OATP1A2 and OATP4A1) are the ones playing an active role in transporting TH to the fetus [ 95 ].…”

The role of the thyroid in polycystic ovary syndrome

“…T3 regulates the synthesis of endometrial protein mRNAs, including leukemia inhibitory factor (LIF), which is important in the implantation process, and glucose transporter 1 (GLUT-1) ( 122 ). In addition, the placenta has T3 and T4 membrane transporters, DIO2 and DIO3 enzymes that regulate thyroid hormones ( 123 ). Oocytes and embryos cultured in a thyroid hormone-rich medium showed improved blastocyst formation, implantation ability, apoptosis rate, and vitality after cryopreservation ( 124 ).…”