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Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta
The ATP‐binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal‐fetal interface. We and others have demonstrated a gestational age‐dependent expression pattern of two ABC transporters, P‐glycoprotein a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307765/ https://www.ncbi.nlm.nih.gov/pubmed/30407748 http://dx.doi.org/10.1111/jcmm.13966 |
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author | Imperio, Guinever E. Javam, Mohsen Lye, Phetcharawan Constantinof, Andrea Dunk, Caroline E. Reis, Fernando M. Lye, Stephen J. Gibb, William Matthews, Stephen G. Ortiga‐Carvalho, Tania Maria Bloise, Enrrico |
author_facet | Imperio, Guinever E. Javam, Mohsen Lye, Phetcharawan Constantinof, Andrea Dunk, Caroline E. Reis, Fernando M. Lye, Stephen J. Gibb, William Matthews, Stephen G. Ortiga‐Carvalho, Tania Maria Bloise, Enrrico |
author_sort | Imperio, Guinever E. |
collection | PubMed |
description | The ATP‐binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal‐fetal interface. We and others have demonstrated a gestational age‐dependent expression pattern of two ABC transporters, P‐glycoprotein and breast cancer resistance protein throughout pregnancy. However, no reports have comprehensively elucidated the expression pattern of all 50 ABC proteins, comparing first trimester and term human placentae. We hypothesized that placental ABC transporters are expressed in a gestational‐age dependent manner in normal human pregnancy. Using the TaqMan(®) Human ABC Transporter Array, we assessed the mRNA expression of all 50 ABC transporters in first (first trimester, n = 8) and third trimester (term, n = 12) human placentae and validated the resulting expression of selected ABC transporters using qPCR, Western blot and immunohistochemistry. A distinct gene expression profile of 30 ABC transporters was observed comparing first trimester vs. term placentae. Using individual qPCR in selected genes, we validated the increased expression of ABCA1 (P < 0.01), ABCA6 (P < 0.001), ABCA9 (P < 0.001) and ABCC3 (P < 0.001), as well as the decreased expression of ABCB11 (P < 0.001) and ABCG4 (P < 0.01) with advancing gestation. One important lipid transporter, ABCA6, was selected to correlate protein abundance and characterize tissue localization. ABCA6 exhibited increased protein expression towards term and was predominantly localized to syncytiotrophoblast cells. In conclusion, expression patterns of placental ABC transporters change as a function of gestational age. These changes are likely fundamental to a healthy pregnancy given the critical role that these transporters play in the regulation of steroidogenesis, immunological responses, and placental barrier function and integrity. |
format | Online Article Text |
id | pubmed-6307765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63077652019-01-04 Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta Imperio, Guinever E. Javam, Mohsen Lye, Phetcharawan Constantinof, Andrea Dunk, Caroline E. Reis, Fernando M. Lye, Stephen J. Gibb, William Matthews, Stephen G. Ortiga‐Carvalho, Tania Maria Bloise, Enrrico J Cell Mol Med Original Articles The ATP‐binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal‐fetal interface. We and others have demonstrated a gestational age‐dependent expression pattern of two ABC transporters, P‐glycoprotein and breast cancer resistance protein throughout pregnancy. However, no reports have comprehensively elucidated the expression pattern of all 50 ABC proteins, comparing first trimester and term human placentae. We hypothesized that placental ABC transporters are expressed in a gestational‐age dependent manner in normal human pregnancy. Using the TaqMan(®) Human ABC Transporter Array, we assessed the mRNA expression of all 50 ABC transporters in first (first trimester, n = 8) and third trimester (term, n = 12) human placentae and validated the resulting expression of selected ABC transporters using qPCR, Western blot and immunohistochemistry. A distinct gene expression profile of 30 ABC transporters was observed comparing first trimester vs. term placentae. Using individual qPCR in selected genes, we validated the increased expression of ABCA1 (P < 0.01), ABCA6 (P < 0.001), ABCA9 (P < 0.001) and ABCC3 (P < 0.001), as well as the decreased expression of ABCB11 (P < 0.001) and ABCG4 (P < 0.01) with advancing gestation. One important lipid transporter, ABCA6, was selected to correlate protein abundance and characterize tissue localization. ABCA6 exhibited increased protein expression towards term and was predominantly localized to syncytiotrophoblast cells. In conclusion, expression patterns of placental ABC transporters change as a function of gestational age. These changes are likely fundamental to a healthy pregnancy given the critical role that these transporters play in the regulation of steroidogenesis, immunological responses, and placental barrier function and integrity. John Wiley and Sons Inc. 2018-11-08 2019-01 /pmc/articles/PMC6307765/ /pubmed/30407748 http://dx.doi.org/10.1111/jcmm.13966 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Imperio, Guinever E. Javam, Mohsen Lye, Phetcharawan Constantinof, Andrea Dunk, Caroline E. Reis, Fernando M. Lye, Stephen J. Gibb, William Matthews, Stephen G. Ortiga‐Carvalho, Tania Maria Bloise, Enrrico Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta |
title | Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta |
title_full | Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta |
title_fullStr | Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta |
title_full_unstemmed | Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta |
title_short | Gestational age‐dependent gene expression profiling of ATP‐binding cassette transporters in the healthy human placenta |
title_sort | gestational age‐dependent gene expression profiling of atp‐binding cassette transporters in the healthy human placenta |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307765/ https://www.ncbi.nlm.nih.gov/pubmed/30407748 http://dx.doi.org/10.1111/jcmm.13966 |
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