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Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth
Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561419/ https://www.ncbi.nlm.nih.gov/pubmed/34169316 http://dx.doi.org/10.1093/hmg/ddab169 |
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author | Karahoda, Rona Robles, Morgane Marushka, Julia Stranik, Jaroslav Abad, Cilia Horackova, Hana Tebbens, Jurjen Duintjer Vaillancourt, Cathy Kacerovsky, Marian Staud, Frantisek |
author_facet | Karahoda, Rona Robles, Morgane Marushka, Julia Stranik, Jaroslav Abad, Cilia Horackova, Hana Tebbens, Jurjen Duintjer Vaillancourt, Cathy Kacerovsky, Marian Staud, Frantisek |
author_sort | Karahoda, Rona |
collection | PubMed |
description | Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively, the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine/transport functions and may contribute to disruption of developmental programming of the fetal brain. |
format | Online Article Text |
id | pubmed-8561419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-85614192021-11-03 Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth Karahoda, Rona Robles, Morgane Marushka, Julia Stranik, Jaroslav Abad, Cilia Horackova, Hana Tebbens, Jurjen Duintjer Vaillancourt, Cathy Kacerovsky, Marian Staud, Frantisek Hum Mol Genet General Article Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively, the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine/transport functions and may contribute to disruption of developmental programming of the fetal brain. Oxford University Press 2021-06-24 /pmc/articles/PMC8561419/ /pubmed/34169316 http://dx.doi.org/10.1093/hmg/ddab169 Text en © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | General Article Karahoda, Rona Robles, Morgane Marushka, Julia Stranik, Jaroslav Abad, Cilia Horackova, Hana Tebbens, Jurjen Duintjer Vaillancourt, Cathy Kacerovsky, Marian Staud, Frantisek Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
title | Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
title_full | Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
title_fullStr | Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
title_full_unstemmed | Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
title_short | Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
title_sort | prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth |
topic | General Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561419/ https://www.ncbi.nlm.nih.gov/pubmed/34169316 http://dx.doi.org/10.1093/hmg/ddab169 |
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