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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
Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T(3)) and L-thyroxine (T(4)) Hormones had been associated with GDM, but the physiopathological meaning of these alte...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685482/ https://www.ncbi.nlm.nih.gov/pubmed/33232364 http://dx.doi.org/10.1371/journal.pone.0242743 |
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author | Gutiérrez-Vega, Sebastián Armella, Axel Mennickent, Daniela Loyola, Marco Covarrubias, Ambart Ortega-Contreras, Bernel Escudero, Carlos Gonzalez, Marcelo Alcalá, Martín Ramos, María del Pilar Viana, Marta Castro, Erica Leiva, Andrea Guzmán-Gutiérrez, Enrique |
author_facet | Gutiérrez-Vega, Sebastián Armella, Axel Mennickent, Daniela Loyola, Marco Covarrubias, Ambart Ortega-Contreras, Bernel Escudero, Carlos Gonzalez, Marcelo Alcalá, Martín Ramos, María del Pilar Viana, Marta Castro, Erica Leiva, Andrea Guzmán-Gutiérrez, Enrique |
author_sort | Gutiérrez-Vega, Sebastián |
collection | PubMed |
description | Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T(3)) and L-thyroxine (T(4)) 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 T(4) (FT(4)), Total T(4) (TT(4)), and Total T(3) (TT(3)) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT(4), TT(4), and TT(3) 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 rT(3) and T(3) using T(4) as a substrate. Mothers with GDM showed higher levels of TT(3) during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT(4), FT(4), and TT(3); 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. |
format | Online Article Text |
id | pubmed-7685482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-76854822020-12-02 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 Gutiérrez-Vega, Sebastián Armella, Axel Mennickent, Daniela Loyola, Marco Covarrubias, Ambart Ortega-Contreras, Bernel Escudero, Carlos Gonzalez, Marcelo Alcalá, Martín Ramos, María del Pilar Viana, Marta Castro, Erica Leiva, Andrea Guzmán-Gutiérrez, Enrique PLoS One Research Article Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T(3)) and L-thyroxine (T(4)) 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 T(4) (FT(4)), Total T(4) (TT(4)), and Total T(3) (TT(3)) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT(4), TT(4), and TT(3) 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 rT(3) and T(3) using T(4) as a substrate. Mothers with GDM showed higher levels of TT(3) during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT(4), FT(4), and TT(3); 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. Public Library of Science 2020-11-24 /pmc/articles/PMC7685482/ /pubmed/33232364 http://dx.doi.org/10.1371/journal.pone.0242743 Text en © 2020 Gutiérrez-Vega et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gutiérrez-Vega, Sebastián Armella, Axel Mennickent, Daniela Loyola, Marco Covarrubias, Ambart Ortega-Contreras, Bernel Escudero, Carlos Gonzalez, Marcelo Alcalá, Martín Ramos, María del Pilar Viana, Marta Castro, Erica Leiva, Andrea Guzmán-Gutiérrez, Enrique 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685482/ https://www.ncbi.nlm.nih.gov/pubmed/33232364 http://dx.doi.org/10.1371/journal.pone.0242743 |
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