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Maternal bile acid transporter deficiency promotes neonatal demise
Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to a...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598356/ https://www.ncbi.nlm.nih.gov/pubmed/26416771 http://dx.doi.org/10.1038/ncomms9186 |
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author | Zhang, Yuanyuan Li, Fei Wang, Yao Pitre, Aaron Fang, Zhong-ze Frank, Matthew W. Calabrese, Christopher Krausz, Kristopher W. Neale, Geoffrey Frase, Sharon Vogel, Peter Rock, Charles O. Gonzalez, Frank J. Schuetz, John D. |
author_facet | Zhang, Yuanyuan Li, Fei Wang, Yao Pitre, Aaron Fang, Zhong-ze Frank, Matthew W. Calabrese, Christopher Krausz, Kristopher W. Neale, Geoffrey Frase, Sharon Vogel, Peter Rock, Charles O. Gonzalez, Frank J. Schuetz, John D. |
author_sort | Zhang, Yuanyuan |
collection | PubMed |
description | Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition. |
format | Online Article Text |
id | pubmed-4598356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45983562015-10-21 Maternal bile acid transporter deficiency promotes neonatal demise Zhang, Yuanyuan Li, Fei Wang, Yao Pitre, Aaron Fang, Zhong-ze Frank, Matthew W. Calabrese, Christopher Krausz, Kristopher W. Neale, Geoffrey Frase, Sharon Vogel, Peter Rock, Charles O. Gonzalez, Frank J. Schuetz, John D. Nat Commun Article Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide. Here we show that maternal cholestasis (due to Abcb11 deficiency) produces neonatal death among all offspring within 24 h of birth due to atelectasis-producing pulmonary hypoxia, which recapitulates the neonatal respiratory distress of human ICP. Neonates of Abcb11-deficient mothers have elevated pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile acid concentrations and increases neonatal survival. We identify pulmonary bile acids as a key factor in the disruption of the structure of pulmonary surfactant in neonates of ICP. These findings have important implications for neonatal respiratory failure, especially when maternal bile acids are elevated during pregnancy, and highlight potential pathways and targets amenable to therapeutic intervention to ameliorate this condition. Nature Pub. Group 2015-09-29 /pmc/articles/PMC4598356/ /pubmed/26416771 http://dx.doi.org/10.1038/ncomms9186 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhang, Yuanyuan Li, Fei Wang, Yao Pitre, Aaron Fang, Zhong-ze Frank, Matthew W. Calabrese, Christopher Krausz, Kristopher W. Neale, Geoffrey Frase, Sharon Vogel, Peter Rock, Charles O. Gonzalez, Frank J. Schuetz, John D. Maternal bile acid transporter deficiency promotes neonatal demise |
title | Maternal bile acid transporter deficiency promotes neonatal demise |
title_full | Maternal bile acid transporter deficiency promotes neonatal demise |
title_fullStr | Maternal bile acid transporter deficiency promotes neonatal demise |
title_full_unstemmed | Maternal bile acid transporter deficiency promotes neonatal demise |
title_short | Maternal bile acid transporter deficiency promotes neonatal demise |
title_sort | maternal bile acid transporter deficiency promotes neonatal demise |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598356/ https://www.ncbi.nlm.nih.gov/pubmed/26416771 http://dx.doi.org/10.1038/ncomms9186 |
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