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Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin

BACKGROUND: Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in t...

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Autores principales: Mathiesen, Line, Bay-Richter, Cecilie, Wegener, Gregers, Liebenberg, Nico, Knudsen, Lisbeth E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269612/
https://www.ncbi.nlm.nih.gov/pubmed/32492052
http://dx.doi.org/10.1371/journal.pone.0233979
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author Mathiesen, Line
Bay-Richter, Cecilie
Wegener, Gregers
Liebenberg, Nico
Knudsen, Lisbeth E.
author_facet Mathiesen, Line
Bay-Richter, Cecilie
Wegener, Gregers
Liebenberg, Nico
Knudsen, Lisbeth E.
author_sort Mathiesen, Line
collection PubMed
description BACKGROUND: Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. METHOD: Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. RESULTS: Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. CONCLUSION: Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels.
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spelling pubmed-72696122020-06-12 Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin Mathiesen, Line Bay-Richter, Cecilie Wegener, Gregers Liebenberg, Nico Knudsen, Lisbeth E. PLoS One Research Article BACKGROUND: Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. METHOD: Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. RESULTS: Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. CONCLUSION: Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels. Public Library of Science 2020-06-03 /pmc/articles/PMC7269612/ /pubmed/32492052 http://dx.doi.org/10.1371/journal.pone.0233979 Text en © 2020 Mathiesen 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
Mathiesen, Line
Bay-Richter, Cecilie
Wegener, Gregers
Liebenberg, Nico
Knudsen, Lisbeth E.
Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
title Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
title_full Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
title_fullStr Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
title_full_unstemmed Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
title_short Maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
title_sort maternal stress and placental function; ex vivo placental perfusion studying cortisol, cortisone, tryptophan and serotonin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269612/
https://www.ncbi.nlm.nih.gov/pubmed/32492052
http://dx.doi.org/10.1371/journal.pone.0233979
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