Placental uptake and metabolism as determinants of pregnancy vitamin D status [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA704615 | ENA |
REPOSITORIES: ENA
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Project description:Placental uptake and metabolism as determinants of pregnancy vitamin D status
| PRJNA704642 | ENA
Project description:Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and 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 fetal and maternal 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 solely 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, including transcriptional activation and inflammatory responses. 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 show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.
2021-02-25 | GSE167429 | GEO
Project description:Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and 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 fetal and maternal 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 solely 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, including transcriptional activation and inflammatory responses. 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 show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.
2021-02-25 | GSE167412 | GEO
Project description:Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and 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 fetal and maternal 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 solely 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, including transcriptional activation and inflammatory responses. 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 show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.
2021-02-25 | GSE167411 | GEO
Project description:Placental uptake and metabolism as determinants of pregnancy vitamin D status [Array]
| PRJNA704645 | ENA
Project description:Placental uptake and metabolism as determinants of pregnancy vitamin D status [ChIP-seq]
| PRJNA704613 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-25 | GSE167431 | GEO
Project description:We studied the effects of vitamin D on the placental proteomic profile
2022-04-01 | PXD011443 | Pride
Project description:Peripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and spontaneous preterm birth from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
2020-02-10 | GSE142974 | GEO
Project description:Vitamin B12 (cobalamin) is the most complex vitamin and essential for many human gut microbes. However, cobalamin is synthesized only by a limited number of bacteria, making many gut microbes dependent on scavenging to meet their cobalamin requirements. Since bacterial densities in the gut are extremely high, competition for cobalamin is severe, making it a keystone micronutrient that shapes human gut microbial communities. Contrasting with Enterobacteria like Escherichia coli which only have one outer membrane (OM) transporter dedicated to B12 uptake (BtuB), members of the dominant genus Bacteroides often encode several vitamin B12 OM transporters together with a conserved array of surface-exposed B12-binding lipoproteins. Here we show, via X-ray crystallography, cryogenic electron microscopy (cryoEM) and molecular dynamics (MD) simulations, that the BtuB1 and BtuB2 transporters from the prominent human gut bacterium Bacteroides thetaiotaomicron form stable complexes with the surface-exposed lipoproteins BtuG1 and BtuG2. The lipoproteins cap the external surface of their cognate BtuB transporter and, when open, capture B12 via electrostatic attraction. After B12 capture, the BtuG lid closes, with concomitant transfer of the vitamin to the BtuB transporter and subsequent transport. We propose that TonB-dependent, lipoprotein-assisted small molecule uptake is a general feature of Bacteroides spp. that is important for the success of this genus in colonising the human gut.
2023-10-18 | PXD038230 | Pride