Na+/I− Symporter and Type 3 Iodothyronine Deiodinase Gene Expression in Amniotic Membrane and Placenta and Its Relationship to Maternal Thyroid Hormones

Abstract

Placental type 3 iodothyronine deiodinase (D3) potentially protects the fetus from the elevated maternal thyroid hormones. Na− symporter (NIS) is a plasma membrane glycoprotein, which mediates active iodide uptake. Our objectives were to establish the distribution of NIS and D3 gene expressions in the placenta and the amniotic membrane and to investigate the relationship between placental D3 and NIS gene expressions and maternal iodine, selenium, and thyroid hormone status. Thyroid hormones, urinary iodine concentration (UIC), and selenium levels were measured in 49 healthy term pregnant women. NIS and D3 gene expressions were studied with the total mRNA RT-PCR method in tissues from maternal placenta (n=49), fetal placenta (n=9), and amniotic membrane (n=9). NIS and D3 gene expressions were shown in the fetal and maternal sides of the placenta and amniotic membrane. Mean blood selenium level was 66±26.5 μg/l, and median UIC was 143 μg/l. We could not demonstrate any statistically significant relationship of spot UIC and blood selenium with NIS and D3 expression (p>0.05). Positive correlations were found between NIS and thyroxine-binding globulin (TBG) (r=0.3, p=0.042) and between D3 and preoperative glucose levels (r=0.4, p=0.006). D3 and NIS genes are expressed in term placenta and amniotic membrane; thus, in addition to placenta, amniotic membrane contributes to regulation of maternofetal iodine and thyroid hormone transmission. Further studies are needed to clarify the relationship between maternal glucose levels and placental D3 expression and between TBG and placental NIS expression.

Iodine as Essential Nutrient during the First 1000 Days of Life

“…Under normal conditions, embryonic tissues have a set of security mechanisms to protect their development. Some of these mechanisms are physical barriers (placenta and ovular membranes) that avoid free transfer of maternal thyroid hormones to the foetus, preventing it from being exposed to the same plasma fluctuations that occur in the maternal bloodstream [ 46 , 47 ]. Another security mechanism is the presence of deiodinase enzymes in the placenta and foetal cerebral tissues [ 48 ].…”

“…Another security mechanism is the presence of deiodinase enzymes in the placenta and foetal cerebral tissues [ 48 ]. Deiodinase enzymes, particularly type 2 (DIO2) present in the developing brain, convert maternal fT4 to tri-iodothyronine (T3), since the direct transfer of maternal T3 is extremely low [ 46 , 48 ].…”

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

“…In the placenta, NIS is expressed at the apical membrane of cytotrophoblasts, where it regulates the transport of I − from the maternal to the fetal circulation, a process critical for normal fetal thyroid function (49, 55). In the salivary glands, NIS is expressed at the basolateral plasma membrane of epithelial ductal cells, which concentrate I − (8, 56–58).…”

Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

“…The ratio of D3 to D1 activity is high during gestation. Developmental changes occur in which D3 activity decreases before delivery (30). Therefore, the increase in placental DIO3 methylation shown here can reduce D3 activity, which may result in early delivery.…”