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Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We...

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Autores principales: Ashley, Brogan, Simner, Claire, Manousopoulou, Antigoni, Jenkinson, Carl, Hey, Felicity, Frost, Jennifer M, Rezwan, Faisal I, White, Cory H, Lofthouse, Emma M, Hyde, Emily, Cooke, Laura DF, Barton, Sheila, Mahon, Pamela, Curtis, Elizabeth M, Moon, Rebecca J, Crozier, Sarah R, Inskip, Hazel M, Godfrey, Keith M, Holloway, John W, Cooper, Cyrus, Jones, Kerry S, Lewis, Rohan M, Hewison, Martin, Garbis, Spiros DD, Branco, Miguel R, Harvey, Nicholas C, Cleal, Jane K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903835/
https://www.ncbi.nlm.nih.gov/pubmed/35256050
http://dx.doi.org/10.7554/eLife.71094
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author Ashley, Brogan
Simner, Claire
Manousopoulou, Antigoni
Jenkinson, Carl
Hey, Felicity
Frost, Jennifer M
Rezwan, Faisal I
White, Cory H
Lofthouse, Emma M
Hyde, Emily
Cooke, Laura DF
Barton, Sheila
Mahon, Pamela
Curtis, Elizabeth M
Moon, Rebecca J
Crozier, Sarah R
Inskip, Hazel M
Godfrey, Keith M
Holloway, John W
Cooper, Cyrus
Jones, Kerry S
Lewis, Rohan M
Hewison, Martin
Garbis, Spiros DD
Branco, Miguel R
Harvey, Nicholas C
Cleal, Jane K
author_facet Ashley, Brogan
Simner, Claire
Manousopoulou, Antigoni
Jenkinson, Carl
Hey, Felicity
Frost, Jennifer M
Rezwan, Faisal I
White, Cory H
Lofthouse, Emma M
Hyde, Emily
Cooke, Laura DF
Barton, Sheila
Mahon, Pamela
Curtis, Elizabeth M
Moon, Rebecca J
Crozier, Sarah R
Inskip, Hazel M
Godfrey, Keith M
Holloway, John W
Cooper, Cyrus
Jones, Kerry S
Lewis, Rohan M
Hewison, Martin
Garbis, Spiros DD
Branco, Miguel R
Harvey, Nicholas C
Cleal, Jane K
author_sort Ashley, Brogan
collection PubMed
description Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D(3) by endocytosis, placental metabolism of 25(OH)D(3) into 24,25-dihydroxyvitamin D(3) and active 1,25-dihydroxyvitamin D [1,25(OH)(2)D(3)], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D(3) and synthesis of 1,25(OH)(2)D(3) demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D(3). We demonstrate that 25(OH)D(3) exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.
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spelling pubmed-89038352022-03-09 Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit Ashley, Brogan Simner, Claire Manousopoulou, Antigoni Jenkinson, Carl Hey, Felicity Frost, Jennifer M Rezwan, Faisal I White, Cory H Lofthouse, Emma M Hyde, Emily Cooke, Laura DF Barton, Sheila Mahon, Pamela Curtis, Elizabeth M Moon, Rebecca J Crozier, Sarah R Inskip, Hazel M Godfrey, Keith M Holloway, John W Cooper, Cyrus Jones, Kerry S Lewis, Rohan M Hewison, Martin Garbis, Spiros DD Branco, Miguel R Harvey, Nicholas C Cleal, Jane K eLife Developmental Biology Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D(3) by endocytosis, placental metabolism of 25(OH)D(3) into 24,25-dihydroxyvitamin D(3) and active 1,25-dihydroxyvitamin D [1,25(OH)(2)D(3)], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D(3) and synthesis of 1,25(OH)(2)D(3) demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D(3). We demonstrate that 25(OH)D(3) exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy. eLife Sciences Publications, Ltd 2022-03-08 /pmc/articles/PMC8903835/ /pubmed/35256050 http://dx.doi.org/10.7554/eLife.71094 Text en © 2022, Ashley et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Ashley, Brogan
Simner, Claire
Manousopoulou, Antigoni
Jenkinson, Carl
Hey, Felicity
Frost, Jennifer M
Rezwan, Faisal I
White, Cory H
Lofthouse, Emma M
Hyde, Emily
Cooke, Laura DF
Barton, Sheila
Mahon, Pamela
Curtis, Elizabeth M
Moon, Rebecca J
Crozier, Sarah R
Inskip, Hazel M
Godfrey, Keith M
Holloway, John W
Cooper, Cyrus
Jones, Kerry S
Lewis, Rohan M
Hewison, Martin
Garbis, Spiros DD
Branco, Miguel R
Harvey, Nicholas C
Cleal, Jane K
Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit
title Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit
title_full Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit
title_fullStr Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit
title_full_unstemmed Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit
title_short Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit
title_sort placental uptake and metabolism of 25(oh)vitamin d determine its activity within the fetoplacental unit
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903835/
https://www.ncbi.nlm.nih.gov/pubmed/35256050
http://dx.doi.org/10.7554/eLife.71094
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