Table 1.
Maternal clinical and biochemical parameters in NGT and GDM pregnancies.
Table 2.
Newborn clinical and biochemical parameters in NGT and GDM pregnancies.
Fig 1.
GDM effect on mRNA levels for deiodinases in human placenta.
Deiodinases (DIO1, DIO2, and DIO3) mRNA levels were measured using Q-RT-PCR (2-ΔΔCT) in placentas from gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnancies. Values are mean ± SE. *P<0.05 compared to NGT pregnancies. n = 20 per group.
Fig 2.
GDM effect on protein levels of deiodinase in placenta.
Deiodinase (DIO) protein levels were measured using western blot in placentae from normal glucose tolerant (NGT) and gestational diabetes mellitus (GDM) pregnancies. (A) DIO2 and (B) DIO3 protein levels in placentae from GDM and NGT pregnancies. β-actin was used as a load control. Results of densitometric analysis were expressed as DIO/β-actin. Values are mean ± SE. *P<0.05 compared to NGT. n = 8–9 per group.
Fig 3.
GDM effect on DIO2 and DIO 3 expression in placental tissue.
DIO2 and DIO3 immunodetection were realized by immunohistochemistry (IHC) in normal glucose tolerant (NTG, A-F) and gestational diabetes mellitus (GDM, G-L) pregnancies. In A-C and G-I 400x magnification, and in D-F and J-L 1000x magnification. White asterisk (*) in A-C and G-I indicates a magnification point in D-F and J-L, respectively. White arrow in D-F and J-L indicates syncytiotrophoblast in the placental tissue. Black bar: 50μm. N = 5 per group.
Fig 4.
GDM effect on 5’- and 5- deiodinase activity in human placenta.
Kinetic of deiodinase activity was measured as T3 or rT3 formation from T4 (0–500 nM, 37°C, 15 min) in placental tissue (300μg placental protein) from Normal Glucose Tolerant (NGT, ○) and Gestational Diabetes Mellitus (GDM, ●) pregnancies. In A and C, T3 and rT3 formation from T4 adjusted to Michaelis-Menten equation. In B and D, Eadie-Hofstee plot from data in A and C, respectively. Mean ± SEM. N = 9 per group.
Table 3.
Kinetic parameters of 5- and 5’- deiodinase activity.
Fig 5.
Proposal model for placental deiodinases in gestational diabetes mellitus (GDM) mothers.
In normal glucose tolerant pregnancies (NGT), the thyroid hormones Free T4 (FT4) and T3 are transported from the maternal blood through the placenta, where their concentrations are regulated by deiodinase 2 (DIO2), which converts T4 to T3; and deiodinase 3 (DIO3), which converts T3 to T2, and T4 to rT3; in order to keep a steady and healthy concentration of thyroid hormones from the mother to the fetus. In GDM however, in order to prevent an influx of an excess of T3 from the mother to the fetus, the expression and activity of DIO3 increases while DIO2 decreases, causing less T3 to be transported to fetal blood by a currently unknown mechanism.