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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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/71094 |
| _version_ | 1828166620073164800 |
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| author | Brogan Ashley Claire Simner Antigoni Manousopoulou Carl Jenkinson Felicity Hey Jennifer M Frost Faisal I Rezwan Cory H White Emma M Lofthouse Emily Hyde Laura DF Cooke Sheila Barton Pamela Mahon Elizabeth M Curtis Rebecca J Moon Sarah R Crozier Hazel M Inskip Keith M Godfrey John W Holloway Cyrus Cooper Kerry S Jones Rohan M Lewis Martin Hewison Spiros DD Garbis Miguel R Branco Nicholas C Harvey Jane K Cleal |
| author_facet | Brogan Ashley Claire Simner Antigoni Manousopoulou Carl Jenkinson Felicity Hey Jennifer M Frost Faisal I Rezwan Cory H White Emma M Lofthouse Emily Hyde Laura DF Cooke Sheila Barton Pamela Mahon Elizabeth M Curtis Rebecca J Moon Sarah R Crozier Hazel M Inskip Keith M Godfrey John W Holloway Cyrus Cooper Kerry S Jones Rohan M Lewis Martin Hewison Spiros DD Garbis Miguel R Branco Nicholas C Harvey Jane K Cleal |
| author_sort | Brogan Ashley |
| collection | DOAJ |
| 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)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 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. |
| first_indexed | 2024-04-12T02:04:17Z |
| format | Article |
| id | doaj.art-1a91c1a9eb944011801afd9ea0ec61b3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:04:17Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1a91c1a9eb944011801afd9ea0ec61b32022-12-22T03:52:35ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.71094Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unitBrogan Ashley0Claire Simner1Antigoni Manousopoulou2Carl Jenkinson3https://orcid.org/0000-0002-1838-5282Felicity Hey4https://orcid.org/0000-0003-2695-4817Jennifer M Frost5https://orcid.org/0000-0002-3057-6313Faisal I Rezwan6https://orcid.org/0000-0001-9921-222XCory H White7https://orcid.org/0000-0002-1619-0174Emma M Lofthouse8https://orcid.org/0000-0002-0175-5590Emily Hyde9https://orcid.org/0000-0001-5084-3709Laura DF Cooke10https://orcid.org/0000-0002-8099-9437Sheila Barton11https://orcid.org/0000-0003-4963-4242Pamela Mahon12https://orcid.org/0000-0003-0661-572XElizabeth M Curtis13https://orcid.org/0000-0002-5147-0550Rebecca J Moon14https://orcid.org/0000-0003-2334-2284Sarah R Crozier15https://orcid.org/0000-0002-9524-1127Hazel M Inskip16https://orcid.org/0000-0001-8897-1749Keith M Godfrey17https://orcid.org/0000-0002-4643-0618John W Holloway18https://orcid.org/0000-0001-9998-0464Cyrus Cooper19https://orcid.org/0000-0003-3510-0709Kerry S Jones20https://orcid.org/0000-0002-7380-9797Rohan M Lewis21https://orcid.org/0000-0003-4044-9104Martin Hewison22https://orcid.org/0000-0001-5806-9690Spiros DD Garbis23https://orcid.org/0000-0002-1050-0805Miguel R Branco24https://orcid.org/0000-0001-9447-1548Nicholas C Harvey25https://orcid.org/0000-0002-8194-2512Jane K Cleal26https://orcid.org/0000-0001-7978-4327The Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomBeckman Research Institute, City of Hope National Medical Center, Duarte, United States; Proteas Bioanalytics Inc, BioLabs at the Lundquist Institute, Torrance, United StatesInstitute of Metabolism and Systems Research, The University of Birmingham, Birmingham, United KingdomNIHR Cambridge Biomedical Research Centre, Nutritional Biomarker Laboratory. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge, United Kingdom; Formerly at MRC Elsie Widdowson Laboratory, Cambridge, CB1 9NL l Merck Exploratory Science Center, Merck Research Laboratories, Cambridge, United StatesCentre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United Kingdom; School of Water, Energy and Environment, Cranfield University, Cranfield, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United Kingdom; Merck Exploratory Science Center, Merck Research Laboratories, Cambridge, United StatesThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom; NIHR Applied Research Collaboration Wessex, Southampton Science Park, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; NIHR Oxford Biomedical Research Center, University of Oxford, Oxford, United KingdomNIHR Cambridge Biomedical Research Centre, Nutritional Biomarker Laboratory. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge, United Kingdom; Formerly at MRC Elsie Widdowson Laboratory, Cambridge, CB1 9NL l Merck Exploratory Science Center, Merck Research Laboratories, Cambridge, United StatesThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomInstitute of Metabolism and Systems Research, The University of Birmingham, Birmingham, United KingdomProteas Bioanalytics Inc, BioLabs at the Lundquist Institute, Torrance, United StatesCentre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United KingdomThe Institute of Developmental Sciences, Human Development and Health, Faculty of Medicine University of Southampton, Southampton, United KingdomPregnancy 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)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 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.https://elifesciences.org/articles/71094placentaVitamin Dfetal programmingepigeneticstranscriptomics |
| spellingShingle | Brogan Ashley Claire Simner Antigoni Manousopoulou Carl Jenkinson Felicity Hey Jennifer M Frost Faisal I Rezwan Cory H White Emma M Lofthouse Emily Hyde Laura DF Cooke Sheila Barton Pamela Mahon Elizabeth M Curtis Rebecca J Moon Sarah R Crozier Hazel M Inskip Keith M Godfrey John W Holloway Cyrus Cooper Kerry S Jones Rohan M Lewis Martin Hewison Spiros DD Garbis Miguel R Branco Nicholas C Harvey Jane K Cleal Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit eLife placenta Vitamin D fetal programming epigenetics transcriptomics |
| 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 | placenta Vitamin D fetal programming epigenetics transcriptomics |
| url | https://elifesciences.org/articles/71094 |
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