High levels of maternal total tri-iodothyronine, and low levels of fetal free L-thyroxine and total tri-iodothyronine, are associated with altered deiodinase expression and activity in placenta with gestational diabetes mellitus

Abstract

Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T3) and L-thyroxine (T4) Hormones had been associated with GDM, but the physiopathological meaning of these alterations is still unclear. Maternal TH cross the placenta through TH Transporters and their Deiodinases metabolize them to regulate fetal TH levels. Currently, the metabolism of TH in placentas with GDM is unknown, and there are no other studies that evaluate the fetal TH from pregnancies with GDM. Therefore, we evaluated the levels of maternal TH during pregnancy, and fetal TH at delivery, and the expression and activity of placental deiodinases from GDM pregnancies. Pregnant women were followed through pregnancy until delivery. We collected blood samples during 10–14, 24–28, and 36–40 weeks of gestation for measure Thyroid-stimulating hormone (TSH), Free T4 (FT4), Total T4 (TT4), and Total T3 (TT3) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT4, TT4, and TT3 in total blood cord at the delivery. Also, we measured the placental expression of Deiodinases by RT-PCR, western-blotting, and immunohistochemistry. The activity of Deiodinases was estimated quantified rT3 and T3 using T4 as a substrate. Mothers with GDM showed higher levels of TT3 during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT4, FT4, and TT3; and an increased TSH level in umbilical cord blood from GDM. Placentae from GDM mothers have a higher expression and activity of Deiodinase 3, but lower Deiodinase 2, than NGT mothers. In conclusion, GDM favors high levels of TT3 during all gestation in the mother, low levels in TT4, FT4 and TT3 at the delivery in neonates, and increases deiodinase 3, but reduce deiodinase 2 expression and activity in the placenta.

Selenoproteins in the Human Placenta: How Essential Is Selenium to a Healthy Start to Life?

“…It was found that, in a low selenium diet, increased T4 and T3 concentrations were found, but there was a reduction in DIO2 and DIO3 expression and activity [ 83 ]. In GDM patients, DIO3 levels were increased; however, there was a significant decrease in DIO2 expression and activity in the placenta compared to normal mothers [ 84 ].…”

Thyroid hormones: Metabolism and transportation in the fetoplacental unit

“…Recent data links a reduction of DIO2 and an increase in DIO3 to the peaked T3 and TSH levels in mothers with gestational diabetes during the third trimester. This is proposed as a response mechanism for ensuring normal levels of fT4 and T3 in the fetus at term (Gutiérrez-Vega et al, 2020). Such changes in DIO2 and DIO3…”

“…Recent data links a reduction of DIO2 and an increase in DIO3 to the peaked T3 and TSH levels in mothers with gestational diabetes during the third trimester. This is proposed as a response mechanism for ensuring normal levels of fT4 and T3 in the fetus at term (Gutiérrez‐Vega et al, 2020). Such changes in DIO2 and DIO3 activity have already been associated with oxidative stress elicited by hydrogen peroxide in astrocytes, (Lamirand et al, 2008) suggesting a similar regulatory mechanism in the placenta.…”

Subklinik Hipotiroidizm ile Gestasyonel Diabetes Mellitus Arasındaki İlişki

“…Placentas from GDM mothers have higher Deiodinase 3 expression and activity, but lower Deiodinase 2 than Normal Glucose Tolerance mothers. [13] According to the literature, hypothyroidism is linked to 6-15 percent of GDM pregnancies. [5,14,15] Additionally, the chance of having GDM is 4.3 times higher in pregnant women who have hypothyroidism.…”