Laboratorio de Patologías del Embarazo, Departamento de Bioquímica Clínica e Inmunología, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile.
Escuela de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad San Sebastián, Chile.
PLoS One. 2020 Nov 24;15(11):e0242743. doi: 10.1371/journal.pone.0242743. eCollection 2020.
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.
妊娠期糖尿病（GDM）的特征是母体 D-葡萄糖代谢异常和胰岛素信号改变。甲状腺激素（TH）三碘甲状腺原氨酸（T3）和 L-甲状腺素（T4）激素的失调与 GDM 有关，但这些改变的生理病理学意义仍不清楚。母体 TH 通过 TH 转运蛋白穿过胎盘，其脱碘酶将其代谢以调节胎儿 TH 水平。目前，GDM 胎盘的 TH 代谢尚不清楚，也没有其他研究评估 GDM 妊娠的胎儿 TH。因此，我们评估了 GDM 妊娠期间的母体 TH 水平，以及分娩时的胎儿 TH 水平，以及 GDM 妊娠胎盘脱碘酶的表达和活性。孕妇在整个孕期进行随访，直至分娩。我们在妊娠 10-14、24-28 和 36-40 周采集血样，以测量正常糖耐量（NGT）和 GDM 母亲的甲状腺刺激激素（TSH）、游离 T4（FT4）、总 T4（TT4）和总 T3（TT3）浓度。此外，我们在分娩时测量脐带血中的胎儿 TSH、FT4、TT4 和 TT3。我们还通过 RT-PCR、western-blotting 和免疫组织化学测量胎盘脱碘酶的表达。通过 T4 作为底物，使用 rT3 和 T3 来估计脱碘酶的活性。GDM 母亲在整个孕期的 TT3 水平较高，在第二和第三孕期 TSH 水平升高，而新生儿 TT4、FT4 和 TT3 浓度较低，脐带血 TSH 水平升高。GDM 母亲的胎盘具有更高的脱碘酶 3 表达和活性，而脱碘酶 2 表达和活性较低。总之，GDM 有利于母亲在整个孕期中 TT3 水平升高，新生儿分娩时 TT4、FT4 和 TT3 水平降低，并增加脱碘酶 3，但减少胎盘脱碘酶 2 的表达和活性。
